COVID-19 Primarily A Vascular Disease

Researchers have discovered the mechanism of the endothelial cell damage caused by the spike protein of the SARS-COV-2. Let’s review this research paper.

Research paper
SARS-CoV-2 Spike Protein Impairs Endothelial Function via Down-regulation of ACE 2
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318902

A good summary of the study
The novel coronavirus’ spike protein plays additional key role in illness
https://www.salk.edu/news-release/the-novel-coronavirus-spike-protein-plays-additional-key-role-in-illness/

eNOS and Nitric Oxide (NO) functions
https://en.wikipedia.org/wiki/Endothelial_NOS

Mitochondrial fission
https://en.wikipedia.org/wiki/Mitochondrial_fission

Potential Management Approach to Long Haul Syndrome - A Review With KoolBeens

I have put together a potential management protocol for the long haul syndrome. Let’s review the draft and get your feedback.

Disclaimer and notes:

Please note that the pathology of the COVID-19 long-haul state is still being researched. Here, the information provided is in the light of the information received so far. As more information becomes available this management approach might become less important or irrelevant. Clinically, this approach has helped a lot of long-haul patients.

Note also: it is possible that instead of presistent virus, there is viral debris that is persisting in the cells.

Mixing Vaccine Types - Oxford University Study

Oxford University is conducting vaccine type mixing for prime dose and the booster dose. In a preliminary data set they have printed the side-effects of mixing the vaccine types. Let’s review the initial reactogenicity data published in Lancet.

Some news: CDC says mask not required for fully vaccinated in certain situations. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html

British airway is trialing highly intelligent 25 seconds saliva based coronavirus test. https://news.sky.com/story/covid-19-ultra-rapid-25-second-coronavirus-test-hailed-as-a-game-changer-in-british-airways-trial-12305272

Now to today’s topic 
Initial reactogenicity data printed in lancet
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01115-6/fulltext

Link with the study protocols
https://comcovstudy.org.uk/study-protocol
Study protocol V5.0
https://comcovstudy.org.uk/files/com-covprotocolv5026-apr-2021finalpdf
Study protocol V2.1
https://comcovstudy.org.uk/files/com-cov2protocolv2123-apr-2021cleanpdf

Increased Breakthrough Rates Of South African Variant From Pfizer-BioNTech Vaccine - An Israeli Study

Let’s review an Israeli Study about Pfizer-BioNTech vaccine and the breakthrough of the South African variant.

Preprint study here
https://www.medrxiv.org/content/10.1101/2021.04.06.21254882v1

Twitter thread by the author(s) of the study
https://twitter.com/SternLab/status/1380922920734711811?s=20

Unrolled thread for the above tweets
https://threadreaderapp.com/thread/1380922920734711811.html

Non-Neutralizing Antibodies From mRNA Vaccines

Researchers at Mount Sinai show that the mRNA based vaccines produce binding and neutralizing antibodies. Let’s review their results.

Study
https://www.medrxiv.org/content/10.1101/2021.03.07.21253098v2

References
https://science.sciencemag.org/content/369/6504/650
https://en.wikipedia.org/wiki/Original_antigenic_sin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853211/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086450/
https://pubmed.ncbi.nlm.nih.gov/26032350/
https://www.consultant360.com/story/back-boost-could-help-future-proof-flu-vaccines
https://www.the-scientist.com/news-opinion/a-brief-history-of-human-coronaviruses-67600

Delta, Viral burden Vaccine Effectiveness Against New SARS-CoV-2 Infections In The UK

A large study from UK shows that vaccine efficacy against new delta infections is reduced. However, vaccine efficacy against severe outcomes seems to be strong. Let's review the study. 

References to the study:
https://www.ndm.ox.ac.uk/covid-19/covid-19-infection-survey/results/new-studies
https://www.ndm.ox.ac.uk/files/coronavirus/covid-19-infection-survey/finalfinalcombinedve20210816.pdf

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional. ...

SARS-COV-2 and blood disorders

https://hemophilianewstoday.com/information-about-covid-19-for-hemophilia-patients/

What are inhibitors?

https://www.feiba.com/us/patient/hemophilia-inhibitors

For example factors VIII or IX clotting factors for hemophilia

Are patients with blood disorders at a higher risk?

Some patients with hemophilia may develop inhibitors and doctors may prescribe them immunosuppressants. These are medicines that suppress the immune system. They may, therefore, make patients more susceptible to infections including SARS-CoV-2.

Plasma therapy is safe from SARS-COV-2 pathogen transmission. Statement by HFA

https://www.hemophiliafed.org/news-stories/2020/03/plasma-protein-therapeutics-association-updated-statement-regarding-coronavirus/

PPTA Statement

https://www.pptaglobal.org/media-and-information/ppta-statements/1055-2019-novel-coronavirus-2019-ncov-and-plasma-protein-therapies

WORLD FEDERATION OF HEMOPHILIA RECOMMENDATIONS FOR HEMOPHILIA PATIENTS

https://www.hemophiliafed.org/news-stories/2020/03/world-federation-of-hemophilia-recommendations-for-hemophilia-patients/

Pandemic and hemoglobin disorders

Sickle cell anemia

Cell sickling in the hypoxic and acidic environment leading to the acute chest syndrome. Plus carboxyamide is mild immunosuppressant that may results in additional risk.

https://www.thalassemia.org/boduw/wp-content/uploads/2020/03/COVID-19-pandemic-and-haemoglobin-disorders_V2.pdf?__cf_chl_jschl_tk__=764a85856edbb5277a06a1c3c87ca9b7e0b49e6d-1589051509-0-Abe-j8o6Rzg3h049qyF_ddqkWDqhgebQLjG1o8390qmQu6_dFzpNjey2hVgV0BQa2RbQRVOBExkb9VdjMTT1bTg_zcvSbhOIZrh98-HkeIZW9jLyJOaUNTX-QVPrFoqJ8SCATKdUcLmnWRWyp2E5kU6n2GPg8fip_6XFf18uLY9fM2Ef45L65yjHhAyE_0aSTwF0B99q5Ivk0JV_WWZAGHZgp4vcbt_2IHqbinjwkUwxBw9D4zzGvdD7Npcc8nxL7ucH79x2BU_D8CXQ2kLMezf11xtbN4DrVQk-zl3XCcEn4jcwKtI6tKGRbcmcRqmgOsq_RrN8T2OEGQUxBhPtgv_ty6oNERuTgpapoO3nzjckPlFqE-UUuIdLLF13WfNxjQ

Hemophilia and COVID-19

von Willebrand Disease and Hemophilia A

https://news.wfh.org/world-federation-of-hemophilia-statement-update-to-covid-19/

Hypercoagulopathy

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156948/

Desmopressin (DDAVP)

https://en.wikipedia.org/wiki/Desmopressin

G6PD deficiency and COVID-19

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166036/

How I treat vWF disease

https://ashpublications.org/blood/article/97/7/1915/53343/How-I-treat-patients-with-von-Willebrand-disease

Pfizer Vaccine For Kids 12 Years and Above Granted EUA By FDA

Pfizer-BioNTech COVID vaccine received FDA’s emergency use authorization for adolescents age 12-15 on 10th May 2021. Let’s review the trial results, dosing, and side effects.

Coronavirus (COVID-19) Update: FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use in Adolescents in Another Important Action in Fight Against Pandemic
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use

Document for the providers
https://www.fda.gov/media/144413/download

PFIZER-BIONTECH ANNOUNCE POSITIVE TOPLINE RESULTS OF PIVOTAL COVID-19 VACCINE STUDY IN ADOLESCENTS
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-biontech-announce-positive-topline-results-pivotal

Mystery Solved - Children Have Better Immune System. AstraZeneca Had Two Severe Events

Children produce more IL-17A and IFN-gamma that results in better virus handling at the innate arm of the immune system stage. Adults on the other hand have more vigorous response from the adaptive arm. This in turn leads to better virus handling in children than adults.

Study

https://stm.sciencemag.org/content/early/2020/09/21/scitranslmed.abd5487

T-Helper 17 cells produce IL-17 (and more cells produce this cytokine as well.)

https://en.wikipedia.org/wiki/T_helper_17_cell

CD161+ cells are memory cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342360/

IL-17A and IFN-gamma producing cells (TH1/TH17)

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123591

https://www.yahoo.com/lifestyle/kids-better-immune-response-covid19-compared-adults-study-173710433.html

https://www.cdc.gov/mmwr/volumes/69/wr/mm6932e3.htm#:~:text=Analysis%20of%20pediatric%20COVID%2D19,to%20an%20intensive%20care%20unit.

Innate lymphoid cells

https://en.wikipedia.org/wiki/Innate_lymphoid_cell

AstraZeneca have two patients with transverse myelitis

https://www.nytimes.com/2020/09/19/health/astrazeneca-vaccine-safety-blueprints.html

https://covid19vaccinetrial.co.uk/files/cov002pisages18-55yearsv11011sept2020pdf

Boosting The Innate Arm of Your Immune System

Fundamental approach:

Strengthen the epithelial cells

Optimize the production of antimicrobial peptides (AMP)

Optimize the immune cells

Keep the cells well nourished

Reduce the stress hormone/molecules’ effect on these cells

Activate the innate arm as soon as possible with better strength

Exercise

Sleep

Epithelial barrier function improvement with diet

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377870/

Immunity In Depth | Linus Pauling Institute | Oregon State University

Set of strategies to enhance the innate immune system

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304486/

Points:

*Phenyl-butyrate and vitamin D help stabilize the lung and the gut epithelium

Antimicrobial peptides AMP: https://en.wikipedia.org/wiki/Antimicrobial_peptides

https://en.wikipedia.org/wiki/Sodium_phenylbutyrate

*Vitamin D promotes the production of macrophages and monocytes, in addition to other immune modulating functions.

*Improve autophagy

Vitamin D helps with autophagy

What cells produce IL-17A?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152582/

Gamma delta T Cells - friends or foe?

https://en.wikipedia.org/wiki/Gamma_delta_T_cell

Interferon Gamma induction can cause cancer

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823949/

Peripheral blood lymphocytes (PBL)

https://en.wikipedia.org/wiki/Peripheral_blood_lymphocyte

BCG Vaccine enhances NK cells activity

https://pubmed.ncbi.nlm.nih.gov/3076601/

Vitamin D

https://youtu.be/prLkrJh38_M

https://youtu.be/wJyT1YSwe-8

Vitamin D is necessary for the production of cathelecidins, beta defensins, and NFkB.

Antibody response bias 

Vitamin C

https://youtu.be/WXULPNF6cTI

What is buffered vitamin C?

https://www.nutriadvanced.co.uk/news/confused-about-the-different-types-of-vitamin-c/

Role of vitamin C as an antioxidant 

https://pubmed.ncbi.nlm.nih.gov/9248859/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098518/

Cimetidine and the NK cells

https://pubmed.ncbi.nlm.nih.gov/3076601/

Cimetidine alone can cause NK cells suppression. However, cimetidine with IFN-alpha can enhance NK cells activity.

Forest bathing

https://environhealthprevmed.biomedcentral.com/articles/10.1007/s12199-008-0068-3

https://www.nature.com/articles/s41423-020-0477-9

Reduce adrenaline by relaxing. Forest bathing. Yoga. Exercise.

Psychological intervention

Mindfulness

Resident memory t cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914228/

Targeting resident memory T cell immunity culminates in pulmonary and systemic protection against Brucella infection

NK cell boost

About Natural Killer Cells & How to Increase & Decrease Them - SelfHacked

Complement

https://rejuvenated.com/how-collagen-shots-and-protein-smoothie-can-help-to-boost-your-immunity/

Treg 17

Vaccine-induced Th17 cells are established as resident memory cells in the lung and promote local IgA responses | Mucosal Immunology

Host Directed Therapy Against Infection by Boosting Innate Immunity

Poor diet boosts innate immunity | Nature

For A Stronger Immunity: Natural Ways To Boost The Immune System | by MILA JONES | Healthcare in America

Boost Your Innate and Adaptive Immunity

https://en.wikipedia.org/wiki/Innate_immune_system

https://www.nytimes.com/2020/05/01/opinion/sunday/coronavirus-vaccine-innate-immunity.html

Immune-Health Supplements: Supporting Innate and Adaptive Immunity | Nutritional Outlook

Harnessing innate immunity to eliminate SARS-CoV-2 and ameliorate COVID-19 disease | Physiological Genomics

Non-specific immunity of BCG vaccine: A perspective of BCG immunotherapy - ScienceDirect

Innate immunity in the lung: how epithelial cells fight against respiratory pathogens | European Respiratory Society

Ivermectin, Abbott, Dogs, ICM Protocol

Zagazig university. Preprint for Ivermectin PROPHYLAXIS

https://clinicaltrials.gov/ProvidedDocs/61/NCT04422561/Prot_SAP_000.pdf

https://www.trialsitenews.com/zagazig-university-randomized-controlled-ivermectin-study-results-confirms-pi-hypothesis-drug-effective-against-covid-19/

University of Baghdad Small Pilot Study

https://www.medrxiv.org/content/10.1101/2020.07.07.20145979v1

https://www.trialsitenews.com/university-of-baghdad-pilot-clinical-trial-ivermectin-plus-hydroxychloroquine-azithromycin-superior-to-no-ivermectin/

Abbott’s rapid PCR test that works in 15 minutes without a machine.

https://www.abbott.com/corpnewsroom/product-and-innovation/upping-the-ante-on-COVID-19-antigen-testing.html

SARS-COV-2 sniffing dogs

https://www.theguardian.com/world/2020/sep/24/close-to-100-accuracy-airport-enlists-sniffer-dogs-to-test-for-covid-19

ICAM protocol by a doctor in Florida

https://bgr.com/2020/09/26/coronavirus-cure-icam-protocol-florida/

COVID-19 Management With Dr. Paul Marik - Author Of MATH+ Protocol

Dr. Marik’s introduction:
Paul E. Marik MD, FCCP, FCCM
Eastern Virginia Medical School

MATH+ Protocol
https://covid19criticalcare.com/math-hospital-treatment/pdf-translations/

EVMS COVID Care for Clinicians
https://www.evms.edu/covid-19/covid_care_for_clinicians/

James Kelly’s question:
My question is about WHAT manufacture or brand does Dr. Marik use when he refers to Ascorbic Acid IV.

What supplements does Dr. Marik take daily to maintain his health, and does he believe in increasing the daily dose that he takes if he has symptoms or the onset of sickness?  (D3, C, B1)?

Doses For Vitamin D, K2, and Calcium

The correct RDA is 8,800 IU per day for vitamin D (according to this article)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463890/

Coimbra Protocol for high dose vitamin D
https://www.coimbraprotocol.com/the-protocol-1

4 ounces of cooked salmon contains approximately 600 IU of vitamin D
https://www.health.harvard.edu/blog/vitamin-d-finding-balance-2017072112070

Ergocalciferol
https://en.wikipedia.org/wiki/Ergocalciferol

Cholecalciferol or Calcifediol in the Management of Vitamin D Deficiency
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352679/

How to adjust the vitamin D dose for overweight or obese persons?
The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers

How much K2, vitamin D, and vitamin A to take together?
Are You Taking Vitamin K2 With Your Vitamin D? - Murray Avenue Apothecary - Blog
https://en.wikipedia.org/wiki/Vitamin_K2
https://www.ncbi.nlm.nih.gov/books/NBK222299/

How much calcium to add?
Vitamin D and calcium supplements: Take them or leave them? - Harvard Health

Are You Taking Too Many Calcium Supplements? – Health Essentials from Cleveland Clinic

Who should receive calcitriol?
calcitriol (vitamin D3) oral/injection | Michigan Medicine

Icelandic Study - Immunity to COVID-19 Lasts Longer (Iceland)

Cases in Iceland
https://www.worldometers.info/coronavirus/country/iceland/

Iceland - how did it get its name?
Iceland is less icy than Greenland
https://cozycampers.is/2019/01/31/iceland-green-greenland-ice/#:~:text=Iceland%20got%20its%20name%20when,from%20every%20blade%20of%20grass.%E2%80%9D

Floki’s character in Vikings
https://en.wikipedia.org/wiki/Gustaf_Skarsg%C3%A5rd

The Power of Antibody-Based Surveillance
https://www.nejm.org/doi/full/10.1056/NEJMe2028079

Original study
https://www.nejm.org/doi/full/10.1056/NEJMoa2026116?query=recirc_curatedRelated_article

Spread of infection in Iceland
https://www.nejm.org/doi/full/10.1056/NEJMoa2006100

Bromhexine Study, SARS-COV-2 Antibody Cocktail

Bromhexine - small study finds it effective for reducing mortality and morbidity in the severe SARS-COV-2 patients
https://bi.tbzmed.ac.ir/Article/bi-23240

Antibody cocktail
https://investor.regeneron.com/news-releases/news-release-details/regenerons-regn-cov2-antibody-cocktail-reduced-viral-levels-and

https://science.sciencemag.org/content/369/6506/1010

https://science.sciencemag.org/content/sci/369/6506/1010.full.pdf

News, Mini Proteins, UVC 222nm, CDC

Researchers have built miniproteins that can bind the receptor binding domain of the SARS-COV-2
Computer-designed proteins may protect against coronavirus | National Institutes of Health (NIH)

Are UVC 222nm lamps useful?
UV Lights and Lamps: Ultraviolet-C Radiation, Disinfection, and Coronavirus | FDA

An example UVC lamp on Amazon (Caution hazardous for you, your pets, and your furniture and fabric.) Read the caution when using the lamp to realize the danger of using these lamps.
https://www.amazon.com/Light-253-7nm-wavelength-Covers-400sq/dp/B07KYVRVX7/ref=redir_mobile_desktop?ie=UTF8&aaxitk=JP30xC5QYyJ2vktX5hjd6A&hsa_cr_id=9451621910901&ref_=sbx_be_s_sparkle_mcd_asin_0

CDC On Oct 7th 2020
CDC adds airborne transmission back to its modes of transmission page
How Coronavirus Spreads | CDC

https://web.archive.org/web/20201006125057/https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html

CDC On August 5th
https://web.archive.org/web/20200805000541/https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html

CDC on September 1st
https://web.archive.org/web/20200901052524/https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html

CDC on September 21st
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html

Previous stance from CDC
CDC on September 20th
https://web.archive.org/web/20200920013006/https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html

Positive PCR Test. Is It Really Positive?

Today we will discuss the CDC recommendation for the utility of the PCR tests. We will also discuss the recommendations by the epidemiologists. And finally, I will provide my commentary.

CDCs Thoughts on PCR
https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

Impacts contact tracing.
Begs the question; if someone had coronavirus fragments, did he/she develop immunity? That means, before blindly reducing the cycle threshold, we should have done a trial test for PCR with Antibodies at both cycle thresholds.

Your Coronavirus Test Is Positive. Maybe It Shouldn’t Be.
https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html

CDCs Clarification
https://www.nytimes.com/2020/08/27/us/politics/trump-coronavirus-testing.html

Faster tests are better
https://www.nytimes.com/2020/08/06/health/rapid-Covid-tests.html

A possible fast test
https://e25bio.com/bobby-brooke-herrera/

CDC article about PCR
https://wwwnc.cdc.gov/eid/article/26/8/20-1246_article

Vaccines Update, NEJM Weighs In

Moderna vows to not enforce patent during the pandemic. It has at least 7 patents for the SARS-COV-2 vaccine.
https://www.wsj.com/articles/moderna-vows-to-not-enforce-covid-19-vaccine-patents-during-pandemic-11602154805

4 participants had grade-3 adverse events in phase I trial of the Moderna vaccine.
https://www.statnews.com/2020/05/26/moderna-vaccine-candidate-trial-participant-severe-reaction/

Older individuals develop robust antibody titers with Moderna vaccine trials in phase I.
https://www.fiercebiotech.com/biotech/moderna-s-covid-19-vaccine-triggers-immune-response-older-adults

Moderna has published their trial protocol
https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf

Pfizer and BionTech mRNA vaccine
Mostly mild to moderate symptoms after the 1st dose of the vaccine in phase III of the trial
https://www.fiercepharma.com/vaccines/pfizer-sees-mostly-mild-to-moderate-safety-profile-phase-3-covid-vaccine-study

Read slides 23 and 24 for the symptom profile
https://s21.q4cdn.com/317678438/files/doc_presentations/2020/09/Covid-19-Programs_FINAL.pdf

A delay maybe important for the following reasons:
1. More time to monitor the participants. Good for the FDA approval.
2. More time for the placebo group to develop COVID-19 severe cases. Without which the vaccine may not be deemed effective.
https://www.fool.com/investing/2020/10/04/what-if-pfizers-and-modernas-coronavirus-vaccine-r/

New England Journal of Medicine weighs in on the state of the pandemic in the USA
https://www.nejm.org/doi/full/10.1056/NEJMe2029812

Testing in the world and daily positivity
https://coronavirus.jhu.edu/testing/international-comparison

Johns Hopkins Dashboard for COVID-19
https://coronavirus.jhu.edu/map.html

Bromhexine Protocol Talk with Dr. Harrison

Dr. Harrison's registry
http://www.harrisoncovid19researchgroup.com/

Twitter thread with questions
https://twitter.com/drbeen_medical/status/1312105968243625984?s=20

A Case of Reinfection. Johnson and Johnson and Eli Lilly Pause Their Trials

A good article to understand the possibility of reinfection and the lack of understanding by the scientists for the reason for the reinfection.
https://www.dw.com/en/lancet-coronavirus-study-explores-risk-of-reinfection/a-55261352

A discussion of reinfection by Lancet
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30783-0/fulltext

Genomic evidence for reinfection with SARS-CoV-2: a case study
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30764-7/fulltext

https://www.ndtv.com/world-news/covid-19-reinfection-casts-doubt-on-virus-immunity-study-2309323

Johnson and Johnson vaccine trial and Eli Lilly’s monoclonal antibody trials are on pause by the drug makers.
https://www.npr.org/sections/coronavirus-live-updates/2020/10/13/923225994/johnson-johnson-vaccine-trial-paused-due-to-unexplained-illness-in-participant

Brain Fog, Myalgia, Depression, And Fatigue In Long-Haulers

Some long-hauler symptoms
https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30606-6/fulltext

Anosmia is an indication that COVID-19 has effected the glymphatic drainage. This results in waste products and inflammatory cytokines to collect in the brain parenchyma leading to the nervous system symptoms like fatigue, depression, brain fog, myalgia, etc.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320866/

What is the glymphatic system?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636982/

Outline of the glymphatic system
https://www.researchgate.net/figure/Outline-of-the-glymphatic-system-This-figure-illustrates-that-perivascular-clearance_fig1_322688508

Can physical assessment techniques aid diagnosis in people with chronic fatigue syndrome/myalgic encephalomyelitis? A diagnostic accuracy study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695376/

Cerebrospinal fluid and its flow
https://en.wikipedia.org/wiki/Cerebrospinal_fluid

Seasonal Coronavirus Specific Antibodies and The Severity of COVID-19

Original antigenic sin
https://en.wikipedia.org/wiki/Original_antigenic_sin

Cross-reactivity
https://en.wikipedia.org/wiki/Cross-reactivity

Severe COVID-19 patients display a back boost of seasonal coronavirus-specific antibodies
https://www.medrxiv.org/content/10.1101/2020.10.10.20210070v1

Less severe course of COVID-19 is associated with elevated levels of antibodies against seasonal human coronaviruses OC43 and HKU1 (HCoV OC43, HCoV HKU1)
https://www.medrxiv.org/content/10.1101/2020.10.12.20211599v1

How antigenic sin reduces the innate response?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685838/

Dr. Zelenko's Interview

Join us to talk about the COVID-19 outpatient treatment with beloved Dr. Zelenko. Dr. Zelenko has been treating COVID-19 with tremendous success in his clinic. He is an outspoken proponent of Hydroxychloroquine based early management protocol. We will discuss the following topics with him today:

* What is Zelenko protocol?
* How did you devise your protocol and did you get any push back for prescribing it?
* HCQ when to use?
* HCQ nebulization, what is the update?
* How does quercetin help? Any data so far for HCQ and Quercetin? Is any one of these better than the other?
* Is there a role of ivermectin?
*  What's the benefit of early treatment
* HCQ based prophylaxis

Link to Zelenko Protocol: https://drive.google.com/file/d/1VnBudq0f0dPtsJRZrRt3XiBDZAYvjlTR/view

Link to Zelenko Prophylaxis: https://docs.google.com/document/d/1i7C_6H1Yq0u8lrzmnzt5N1JHg-b5Hb0E3nLixedgwpQ/edit

Twitter thread to see the audience questions: https://twitter.com/drbeen_medical/status/1301559780146737153

LATEST STUDY: Early Management With Hydroxychloroquine - By Dr. Zelenko

Link to the study
https://www.sciencedirect.com/science/article/pii/S0924857920304258

Ivermectin Works For COVID-19 - LATEST STUDIES

Original in-vitro study about Ivermectin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129059/

A study from Bangladesh found that Ivermectin + Doxyclyclin significantly reduces mortality and morbidity in COVID-19 patients.
https://clinicaltrials.gov/ct2/show/study/NCT04523831

A systemic review of the antiviral activity of Ivermectin
https://www.nature.com/articles/s41429-020-0336-z

https://journal.chestnet.org/article/S0012-3692(20)34898-4/fulltext
PDF for the above study after it was accepted
https://journal.chestnet.org/article/S0012-3692(20)34898-4/pdf
Pre-print of the above study
https://www.medrxiv.org/content/10.1101/2020.06.06.20124461v2

A search of various Ivermectin studies for your reading pleasure
https://clinicaltrials.gov/ct2/results?cond=Covid19&term=ivermectin&cntry=&state=&city=&dist=

Iota carrageenan and Ivermectin oral drops
https://clinicaltrials.gov/ct2/show/results/NCT04425850?term=ivermectin&cond=Covid19&draw=2

High Dose Thiamine and Cytokine Storm

Link to the study discussed
https://www.medrxiv.org/content/10.1101/2020.08.23.20177501v1

Thiamine
https://youtu.be/IKbUsn1nK1s

T-Helper 17 cells
https://en.wikipedia.org/wiki/T_helper_17_cell

Interleukin 8
https://en.wikipedia.org/wiki/Interleukin_8

FDA Approves Remdesivir for COVID-19 

New England Journal of Medicine (NEJM)
https://www.nejm.org/doi/full/10.1056/NEJMoa2007764

Trial sponsored by: National Institute of Allergy And Infectious Diseases (NIAID)
https://www.niaid.nih.gov/

FDA Approves Remdesivir
https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19

Emergency Use Drugs Authorized for COVID-19 by FDA
https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs

Coronavirus Treatment Acceleration Program (CTAP)
https://www.fda.gov/drugs/coronavirus-covid-19-drugs/coronavirus-treatment-acceleration-program-ctap

WHO Study says Remdesivir does not work
https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1
https://www.reuters.com/article/health-coronavirus-remdesivir-idUSL4N2H63XG

White House Coronavirus Task Force
https://en.wikipedia.org/wiki/White_House_Coronavirus_Task_Force

Bureaucracy
JENKINS: The modern scourge of bureaucratic doublespeak | News | gwinnettdailypost.com

An interview with Fauci
‘I’m going to keep pushing.’ Anthony Fauci tries to make the White House listen to facts of the pandemic | Science | AAAS

How to interpret hazard ratio?
https://s4be.cochrane.org/blog/2016/04/05/tutorial-hazard-ratios/

ACT Trial (ACTT)
https://clinicaltrials.gov/ct2/show/NCT04280705

Dr. Fauci and masks
https://www.reuters.com/article/uk-factcheck-fauci-outdated-video-masks-idUSKBN26T2TR

Hydroxychloroquine Some Studies Are Still Confusing

WHO - It does not work
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters?gclid=EAIaIQobChMI3tmqzryU7AIVvh-tBh3IVARCEAMYASAAEgLli_D_BwE#chloroquine

Study from Belgium - it works
https://www.sciencedirect.com/science/article/pii/S0924857920303423?fbclid=IwAR07sq6JD1_ZutyHvlBfmexMjaMYhid-plTIVFIJXJqCOC04rLRaIIUCOJs

It works
https://www.medrxiv.org/content/10.1101/2020.09.30.20204693v1

Veterans Affairs Healthcare System - It does not work
https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30305-2/fulltext#%20

Hospitalization percentages
https://gis.cdc.gov/grasp/covidnet/COVID19_5.html

Ranitidine Bismuth Citrate (RBC) For COVID-19

Ranitidine
https://en.wikipedia.org/wiki/Ranitidine

Article on the efficacy of the Ranitidine Bismuth Citrate
https://www.sciencedaily.com/releases/2020/10/201015101807.htm

SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271831/

Mechanism of Nucleic Acid Unwinding by SARS-CoV Helicase
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352918/

Nsp13 gene on open reading frame 1ab (ORF1ab), pp1ab
https://www.mdpi.com/2077-0383/9/4/1225/htm

Good News About BioNTech and Pfizer’s Vaccine

Pfizer says that BioNTech’s vaccine has proved to be 90% effective during their interim analysis of the phase III trial including data up to 8th November 2020. They are hopeful to provide the safety data of two months as required by FDA by the third week of November. At that point they will apply for the emergency use authorization.

Pfizer’s update about the vaccine:
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against

Pfizer vaccine protocol PDF document:
https://pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-11/C4591001_Clinical_Protocol_Nov2020.pdf

Pfizer vaccine information:
https://www.pfizer.com/science/coronavirus

WAPO article about the vaccine
https://www.washingtonpost.com/health/2020/11/09/pfizer-coronavirus-vaccine-effective/

Experts weigh in on Pfizer’s vaccine
https://www.yahoo.com/lifestyle/experts-weigh-in-pfizer-covid-19-vaccine-171625902.html

How mRNA vaccines may be delivered
https://www.mdpi.com/1999-4923/12/2/102/htm

mRNA packaged in a lipid nanoparticle is a good route of introducing the mRNA to our cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439223/

An interim analysis is the data processing and understanding the benefit of a treatment before all the data collection is completed. This allows the monitoring committees to decide to continue the study or halt it in case of obvious harmful results observed.
https://en.wikipedia.org/wiki/Interim_analysis

Good News Ivermectin Reduces Mortality In COVID-19 Patients

A study from Dominican Republic shows that IVM reduces mortality to 1% compared to 3% mortality observed in worldwide statistics. Let’s review the study design, prescription, dosage, and the results from this study.

https://www.medrxiv.org/content/10.1101/2020.10.29.20222505v1

Mouth Washes That Inactivate Coronaviruses

Study finds the SARS-COV-2 is inactivated by some of the oral rinsing products
https://academic.oup.com/jid/article/222/8/1289/5878067

Study finds that some mouth washes and nasal rinses help reduce virus load by greater than 90%
https://onlinelibrary.wiley.com/doi/10.1002/jmv.26514

An article for the above study
https://www.yahoo.com/lifestyle/mouthwashes-could-inactivate-human-coronaviruses-that-cause-the-common-cold-232959144.html

How to perform a nasal rinse
https://youtu.be/tVZLqXaE7-8

A study in Malaysia finds rapid virus clearing in SARS-COV-2 patients
https://clinicaltrials.gov/ct2/show/study/NCT04410159?term=mouth+wash&recrs=e&rslt=With&cond=covid&draw=2&rank=1

Polyvidone
https://en.wikipedia.org/wiki/Polyvinylpyrrolidone

Two Studies About Vitamin C and Vitamin D

Understand a little bit about the p value. p value greater than 0.05 means insignificant result. We think you will love this blog post about the p value.
https://blog.minitab.com/blog/understanding-statistics/what-can-you-say-when-your-p-value-is-greater-than-005

Dr. Paul Marik’s small study about the role of vitamin C
https://pubmed.ncbi.nlm.nih.gov/32964205/#affiliation-4

Another small and possibly poor study about vitamin C. Still, discussing for educational purposes.
https://www.researchsquare.com/article/rs-52778/v2#comments

Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults 

Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults 
https://www.imperial.ac.uk/media/imperial-college/institute-of-global-health-innovation/MEDRXIV-2020-219725v1-Elliott.pdf

Don’t panic though
https://coronavirus.medium.com/dont-freak-out-over-that-waning-covid-19-antibodies-study-8705e7dbf1d8

Memory T cells participate as well
https://www.sciencedirect.com/topics/immunology-and-microbiology/memory-t-cell

Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion
https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v1

SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
https://www.nature.com/articles/s41586-020-2550-z

Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors
https://www.medrxiv.org/content/10.1101/2020.04.17.20061440v1

Affinity maturation
https://en.wikipedia.org/wiki/Affinity_maturation

How does SARS-COV-2 Disrupt Our Defense?

A research paper shows how the SARS-COV-2 disrupts mRNA splicing, protein translation, and protein trafficking in our cells. This leads to reduced production of interferons. Which in turn, causes reduced viral defense by the host cells.
https://www.sciencedirect.com/science/article/pii/S0092867420313106

Preliminary COVID-19 Cytokine Storm Prediction Criteria

Researchers from Temple University studied the current cytokine storm prediction criteria and found them less sensitive and specific. They have created a new preliminary criteria to predict COVID related cytokine storm.
Study article
https://ard.bmj.com/content/early/2020/09/25/annrheumdis-2020-218323

Introduction To P Values and Power

In this talk we will discuss at a high level the following concepts:
** Null hypothesis
** Type 1 error
** Type 2 error
** Power
** P value

We will use data from this study to calculate the p values
https://clinicaltrials.gov/ct2/show/results/NCT04523831

We will use the following calculator for the Chi Square calculation
https://www.socscistatistics.com/tests/chisquare/default2.aspx

Cloth Masks Do Not Cause Hypoxia

A study shows that the cloth masks do not cause hypoxia.
https://jamanetwork.com/journals/jama/fullarticle/2772655?appid=scweb&alert=article

Study - Antibody Immunity to SARS-COV-2 Lasts And Matures At 6 Months

Evolution of Antibody Immunity to SARS-CoV-2
https://www.biorxiv.org/content/10.1101/2020.11.03.367391v1

Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection
https://www.biorxiv.org/content/10.1101/2020.11.01.362319v1

AstraZeneca Vaccine is 62% and 90% Effective

AstraZeneca (Oxford college’s partner) has released the interim results for the trials conducting in the UK and Brazil.

https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html

Safety data study
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext

Dr. Paul Marik Discusses His I-MASK+ Protocol

Twitter questions: https://twitter.com/drbeen_medical/status/1330957294624882688?s=21

Today we will have Dr. Paul Marik with us. He is the author of MATH+ and now, I-MASK+ protocol for the management of the COVID-19.

Study - Honey and Nigella Sativa For COVID-19

Study on clinical trials site
https://clinicaltrials.gov/ct2/show/NCT04347382

Preprint on MedRxIV.Org
https://www.medrxiv.org/content/10.1101/2020.10.30.20217364v3

Benefits of Nigella Sativa
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347483/

Quinones
https://en.wikipedia.org/wiki/Quinone

Thymoquinoes
https://en.wikipedia.org/wiki/Thymoquinone

Quinine
https://en.wikipedia.org/wiki/Quinine

Which Vaccine Is Better?

UK approves Pfizer/BioNTech vaccine. They become the first country in the world to approve a vaccine outside of the trials.
https://www.bbc.com/news/health-55145696

Pfizer/BioNTech vaccine was submitted to FDA for approval on 10th November 2020. Expected meeting to review and possibly approve is 10th December 2020 (US.)
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine

Moderna’s vaccine is also submitted for the FDA approval on 30th November. Expected FDA meeting to review and possibly approve is 17th December.
https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-primary-efficacy-analysis-phase-3-cove-study

Ultra-cold storage requirements
https://www.reuters.com/article/health-coronavirus-vaccines-distribution/why-pfizers-ultra-cold-covid-19-vaccine-will-not-be-at-the-local-pharmacy-any-time-soon-idUSKBN27P2VP

Vaccine storage requirements and logistics.
https://www.paho.org/immunization/toolkit/resources/partner-pubs/ebook/Chapter5-Vaccine-Storage-and-Handling.pdf?ua=1

For fun here is a good link to read-up on the physics of the ultra-cold storage units.
https://www.wired.com/story/physics-of-materials-minus-80-degrees-celsius/

A good discussion about the cold-storage needs
https://www.nbcphiladelphia.com/news/coronavirus/70-degrees-how-philly-plans-to-store-a-covid-19-vaccine-that-must-be-kept-ultra-cold/2592559/

WHO’s guidelines for cold-chain logistics
https://www.who.int/immunization/documents/IIP2015_Module2.pdf

New Strain From UK - Should We Worry?

A new strain of the SARS-COV-2 was identified in UK on 20th September. Since then this strain has spread slowly. However, in December it has become the dominant strain in London.

This strain has been named ‘VUI – 202012/01’ (the first Variant Under Investigation in December 2020).

UK Government’s article
https://www.gov.uk/government/news/phe-investigating-a-novel-variant-of-covid-19

Mutations in this strain
https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563

H69/V70 deletion has been already found in many countries independently. It is also found in minks.
https://www.medrxiv.org/content/10.1101/2020.11.10.20228528v1

More strains
https://www.news-medical.net/news/20201214/Emergence-of-resistant-SARS-CoV-2-variant-in-immunocompromised-patient-following-therapeutic-antibody-use.aspx

This particular clade B117
https://nextstrain.org/groups/neherlab/ncov/S.N501?c=gt-S_501,69&f_country=United%20Kingdom&label=mlabel:20B/C5388A&p=grid

What is an antigen?
https://en.wikipedia.org/wiki/Antigen

What is an epitope?
https://en.wikipedia.org/wiki/Epitope

Minks and Masks (WHO AND CDC)

Denmark has a mutant SARS-COV-2 strain in minks. This strain according to the preliminary findings from the WHO is less responsive to the neutralizing antibodies. Denmark is going to cull all these minks. WHO at the moment does not believe that travel restrictions are needed. An error in my opinion.
https://www.who.int/csr/don/06-november-2020-mink-associated-sars-cov2-denmark/en/

CDC says that cloth masks especially polypropylene and high thread count cotton masks are important to reduce the SARS-COV-2 spread and to open up the society.
https://www.cdc.gov/coronavirus/2019-ncov/more/masking-science-sars-cov2.html

Erratum: the spelling of Regeneron is incorrect in the title slide due to human error. We are fixing this error. 

Antibody cocktail
https://investor.regeneron.com/news-releases/news-release-details/regenerons-regn-cov2-antibody-cocktail-reduced-viral-levels-and

https://science.sciencemag.org/content/369/6506/1010

https://science.sciencemag.org/content/sci/369/6506/1010.full.pdf

Allergic Reactions to Pfizer/BionTech Vaccine in UK

Two healthcare workers in UK have experienced anaphylactoid reactions from the Pfizer COVID vaccine. Anaphylactoid reaction can have rashes, difficulty in breathing, and drop in blood pressure. An anaphylactoid reaction is different from an anaphylaxis reaction which can be life-threatening. Both healthcare workers are recovering well.

A notable point is that both healthcare workers who developed the allergic reaction were severely allergic to other substances as well and carried adrenaline injections with them.

MHRA has advised against administering the Pfizer vaccine to anyone that has similar allergic reaction history.

Despite the allergies the vaccination program continues to roll out in UK.

Anaphylaxis
https://en.wikipedia.org/wiki/Anaphylaxis

Basophils
https://en.wikipedia.org/wiki/Basophil

Mast cells
https://en.wikipedia.org/wiki/Mast_cell

Pfizer vaccine side-effects
https://news.yahoo.com/just-got-best-look-yet-140514936.html

FDA briefing about the Pfizer vaccine side effects.
https://www.fda.gov/media/144245/download

FDA says that the Pfizer vaccine is safe and effective
https://news.yahoo.com/fda-says-pfizer-vaccine-safe-150356697.html

Allergy warning by MHRA
https://www.bbc.com/news/health-55244122

A great explainer for the vaccine allergic reactions
https://www.nbc29.com/2020/12/09/explainer-allergic-reactions-vaccines-rare-short-lived/

Canada and Bahrain also approve Pfizer/BionTech’s vaccine
https://globalnews.ca/news/7474273/pfizer-emergency-use-coronavirus-vaccine-canada/

UAE approves SinoPharm's vaccine
https://www.khaleejtimes.com/coronavirus-pandemic/uae-vaccine-for-coronavirus-sinopharms-jab-approved

Please Watch - Pregnant Women and COVID-19

Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China
https://jamanetwork.com/journals/jama/fullarticle/2761659

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30360-3/fulltext

Universal Screening for SARS-CoV-2 in Women Admitted for Delivery
https://www.nejm.org/doi/full/10.1056/NEJMc2009316

Antibodies in Infants Born to Mothers With COVID-19 Pneumonia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099444/

Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392880/

Ivermectin Alone More Effective Than Ivermectin and Doxycycline

Study results
https://www.ijidonline.com/article/S1201-9712(20)32506-6/fulltext

 In the 5-day ivermectin group there was significant drop of CRP and LDH by day-7 which are indicators of disease severity. It is noteworthy that the viral nucleic acid cycle threshold value (indicator of viral load) significantly dropped compared to the placebo group on day-7 and day-14. In the absence of co-morbidity, a 5-day course of ivermectin treatment showed faster SARS-CoV-2 virus clearance compared to the placebo arm (9 vs.13 days; P = 0.02).

Sponsoring company’s article
https://www.icddrb.org/quick-links/press-releases?id=99&task=view

Study on the clinicaltrial site
https://clinicaltrials.gov/ct2/show/NCT04407130?term=ivermectin&cond=covid&draw=2&rank=26

Another article on this study
https://www.aa.com.tr/en/asia-pacific/bangladesh-ivermectin-shows-promise-in-treating-virus/2068885

Vaccination and Vaccines’ Updates (Dec 28th 2020)

Moderna has an allergic reaction as well.
https://www.nbcboston.com/news/coronavirus/boston-doctor-who-had-allergic-reaction-to-moderna-vaccine-describes-experience/2266946/

71% Americans are willing to be vaccinated. Up from 63% in August
https://www.npr.org/sections/coronavirus-live-updates/2020/12/15/946761737/poll-americans-are-growing-less-reluctant-to-take-covid-19-vaccine

Bloomberg’s vaccine tracker
https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/

John Hopkins’ Vaccine Tracker
https://coronavirus.jhu.edu/region/us/colorado#vaccine-tracker

Pfizer’s vaccines for the USA
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-supply-us-100-million-additional-doses
Pfizer is asked to provide 200 million doses by July 31, 2021.

Moderna’s vaccine doses for the USA
https://investors.modernatx.com/news-releases/news-release-details/us-government-exercises-1st-option-additional-100-million-doses
Moderna is asked to provide 200 million doses by the end of the second quarter 2021. With an option to purchase and additional 300 million doses.

A great article by USA Today about the vaccine data collection and processing.
https://www.usatoday.com/in-depth/news/2020/12/16/covid-19-vaccine-data-supply-chain-software-immunization-registry-tiberius/3879655001/

1. A doctor in Boston developed a reaction to Moderna. Doctor was allergic to shellfish.
2. US promised to roll-out vaccine to 20 million by the end of the year. We only have about two millions so far (in two weeks.) It’s going slow.
3. 11.4 Million doses have been sent out to various centers in the US.
4. There is possible lag of reporting, but, that will not be in millions.
5. CDC requires two days of vaccine quality assurance when it reaches its destination before its administration.
6. End of the first week is the target. I have been saying that all along.
7. Moderna has started shipping as well. More than 3,500 centers will receive Moderna compared to about 600 centers for Pfizer.
8. Most of this seems to be logistics. Brining the vaccine, quality assurance, allocating staff to administer the vaccine. And, to assign personnels to get the vaccines.
9. In some states the vaccines are becoming available for the long term care facilities, but, still not injected as efficiently.
10. When a dose is given to someone, a dose is kept in reserve for their second shot.

Vaccine types:
Chemically inactivated virus.
Weakened virus
mRNA
https://www.healthline.com/health-news/china-has-been-vaccinating-its-population-for-weeks-what-we-know

Sinopharm is not very transparent for its vaccine data
https://www.nature.com/articles/d41586-020-03563-z

US population
https://www.census.gov/prod/cen2010/briefs/c2010br-03.pdf

COVID Long Haulers - Discussion With Dr. Bruce Patterson

Twitter link
https://twitter.com/drbeen_medical/status/1338612034125004800?s=20

Today we will discuss COVID-19 long-haul patients. We will discuss the following topics:
1. Diagnosis 
2. Monitoring 
3. Treatment
4. Possible Causes

AstraZeneca Vaccine And Our Nucleus

In the talk today we will discuss how the adenovirus that makes AstraZeneca vaccine will enter our cells, reach our nucleus, and insert its genetic material into our nucleus. We will discuss the events that transpire in our cell’s nucleus once the adenovirus DNA is in there.

AstraZeneca vaccine EUA in UK
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/astrazenecas-covid-19-vaccine-authorised-in-uk.html

AstraZeneca vaccine authorization in India and six other countries
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/serum-institute-of-india-obtains-emergency-use-authorisation-in-india-for-astrazenecas-covid-19-vaccine.html

Adenovirus replication (keep in mind that the adenovirus in AstraZeneca vaccine is not able to replicate.)
https://www.cronodon.com/BioTech/Adenovirus.html

Adenovirus
https://en.wikipedia.org/wiki/Adenoviridae

How an adenovirus enters, and reaches the nucleus of our cells?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578361
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429625/

How various viruses replicate?
https://en.wikipedia.org/wiki/Viral_replication

Adenovirus related article
https://www.bbc.com/news/health-55308216

A good article about the adenovirus based vaccines
https://www.news-medical.net/health/What-are-Adenovirus-Based-Vaccines.aspx

Virus based vectors to carry genes for vaccines and cancers
https://en.wikipedia.org/wiki/Viral_vector#Adenoviruses

Will the vaccine continue to make spike proteins?

Let’s talk about what happens to the mRNA from a vaccine and how long the spikes proteins are made.

http://oregonstate.edu/instruction/bi314/summer09/processing.html

Lifetime of mRNA on average can range from 1-3 minutes. Sometimes days.
https://en.wikipedia.org/wiki/Messenger_RNA

Number of ribosomes in a cell is about 10 millions
https://www.sciencemag.org/news/2017/06/there-are-millions-protein-factories-every-cell-surprise-they-re-not-all-same

Rate of mRNA translation is about 6 amino acids per second.
http://book.bionumbers.org/what-is-faster-transcription-or-translation

mRNA decay
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC87307/
https://core.ac.uk/download/pdf/81148404.pdf
http://genesdev.cshlp.org/content/3/1/60.full.pdf
https://pubmed.ncbi.nlm.nih.gov/7736570/
https://pubmed.ncbi.nlm.nih.gov/15596551/

mRNA decay by various enzymes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347869/

A start codon
https://en.wikipedia.org/wiki/Start_codon

A stop codon
https://en.wikipedia.org/wiki/Stop_codon

https://en.wikipedia.org/wiki/Cap_binding_complex

https://en.wikipedia.org/wiki/Five_prime_untranslated_region

https://en.wikipedia.org/wiki/Polyadenylation

https://www.nature.com/articles/s41401-020-0485-4

Allergic Reactions and Death By Pfizer-BioNTech Vaccine

US Infections, Hospitalizations, and Deaths according to World O Meter
https://www.worldometers.info/coronavirus/country/us/

An assessment of symptomatic and asymptomatic SARS-COV-2 infections in the US.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774584

CDC dashboard for the vaccine distribution and administration
https://covid.cdc.gov/covid-data-tracker/#vaccinations

Bloomberg dashboard for vaccination
https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/

CDC on the allergic reactions and anaphylaxis by Pfizer-BioNTech vaccine
https://www.cdc.gov/mmwr/volumes/70/wr/mm7002e1.htm?s_cid=mm7002e1_w

Doctor dies after Pfizer-BioNTech vaccine
https://www.nytimes.com/2021/01/12/health/covid-vaccine-death.html

CDC confirms 29 anaphylaxis reactions
https://www.aappublications.org/news/2021/01/06/covid19-vaccines-anaphylaxis-010621

COVID-19 infections and deaths globally
https://coronavirus.jhu.edu/map.html

New Brazilian Strain P.1 Manaus (SARS-COV-2)
A Brazilian variant of the SARS-COV-2 has 24 mutations in it. It includes some mutations from the UK strain and some from the South African strain. However, it is thought, that these mutations have occurred independently.

Let’s look at these mutations together.

Genomic characters of P.1 Manaus lineage/variant
https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586

Important mutations
https://www.gisaid.org/references/gisaid-in-the-news/novel-variant-combination-in-spike-receptor-binding-site/

Brazilian lineages
https://cov-lineages.org/lineages/lineage_B.1.1.28.html

Emerging variants
https://www.bmj.com/content/372/bmj.n158

What are phylogenetic changes?
https://en.wikipedia.org/wiki/Phylogenetics

SARS-COV-2 sequence data
https://asm.org/Articles/2020/October/SARS-CoV-2-Sequencing-Data-The-Devil-Is-in-the-Gen

A comparison of B.1.1.7
https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563

Cytokine Storm with ADE - Antibody-dependent Enhancement of Coronavirus

In today’s discussion we will go over the antibody dependent enhancement mechanisms, and will figure out if the coronavirus is affected by this mechanism.

Special comment by Dr. Mobeen about the possibility of cytokine and its solution in light of the ADE concepts.

A good article to go over
https://www.sciencedirect.com/science/article/pii/S1201971220307311

Johnson and Johnson Vaccine - Interim Results For Phase 1 and 2

JNJ has released their phase 1 and 2a trial results. Let’s look into the results in this talk.

Article with the phase 1 and 2a trial results
https://www.nejm.org/doi/full/10.1056/NEJMoa2034201

PDF for the Phase 1 and 2a trial results
https://www.nejm.org/doi/pdf/10.1056/NEJMoa2034201?articleTools=true

Janssen vaccine technology
https://www.janssen.com/emea/emea/janssen-vaccine-technologies

Vaccine storage comparisons
https://www.phillyvoice.com/johnson-johnson-covid-19-vaccine-timeline-phase-3-trial-results/

South African SARS-COV-2 Variant - 501.V2

501.V2 variant
https://en.wikipedia.org/wiki/501.V2_variant

The Second Covid-19 wave in South Africa: Transmissibility & a 501.V2 variant
https://www.scribd.com/document/488618010/Full-Presentation-by-SSAK-18-Dec

Denmark’s Cluster 5 Variant
Thought to be extinct now.
https://en.wikipedia.org/wiki/Cluster_5

UK’s variant Variant of Concern 202012/01
https://en.wikipedia.org/wiki/Variant_of_Concern_202012/01

What are base pairs (bp)?
https://en.wikipedia.org/wiki/Base_pair#Length_measurements

SARS-COV-2 Receptor binding motif
https://www.caymanchem.com/product/30428/sars-cov-2-surface-glycoprotein-receptor-binding-motif

References for South African variant
https://www.krisp.org.za/news.php?id=460

https://www.sciencemediacentre.org/expert-reaction-to-south-african-variant-of-sars-cov-2-as-mentioned-by-matt-hancock-at-the-downing-street-press-briefing/

https://www.scribd.com/document/488618010/Full-Presentation-by-SSAK-18-Dec

What is GISAID
https://en.wikipedia.org/wiki/GISAID

What Antibody Levels Are Necessary For COVID-19 Protection?

For the first time researchers have found out the antibody threshold levels that are protective. This knowledge is crucial for vaccine development, monoclonal antibodies titers, for the convalescent plasma therapies.

Let’s look at the study.

https://www.nature.com/articles/s41586-020-03041-6

Moderna Vaccine Recommended by The FDA Advisory Committee

Today the vaccine and related biological products advisory committee (VRBPAC) met to review and recommend the Moderna’s mrna-1273 vaccine for COVID-19. The committee recommended the issuance of emergency use authorization (EUA) with a 95% yay.

Moderna’s EUA request (presentation):
https://www.fda.gov/media/144583/download

The voting question was:
https://www.fda.gov/media/144586/download
Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

Again 95% said yes to the above statement.

FDA’s meeting presentation
https://www.fda.gov/media/144585/download

FDA’s meeting information and material
https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-december-17-2020-meeting-announcement

FDA’s briefing document
https://www.fda.gov/media/144434/download

FDA’s meeting announcement
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-announces-advisory-committee-meeting-discuss-second-covid-19-vaccine

Vitamin D, Dust and COVID-19

Vitamin D’s effect is reduced by dust. Hence, the severity of COVID-19 is increased. Let’s see how?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326088/

Who Will Get The COVID Vaccine First? CDC Recommendation

CDC Interim Recommendation For Immunization Practices
Authorized by FDA and approved by ACIP
Healthcare personnel and long-term resident community.

https://www.cdc.gov/vaccines/acip/index.html

Presentation used to vote for the recommendations
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2020-12/COVID-02-Dooling.pdf

https://www.ustream.tv/channel/VWBXKBR8af4

Approved by 13 yay and 1 nay

Healthcare personnel 
Residents of the long-term care facilities

Is India Mistaken To Approve Covaxin Vaccine?

Vero cell line (for virus culture)
https://en.wikipedia.org/wiki/Vero_cell

Beta-propiolactone (for inactivating the virus)
https://en.wikipedia.org/wiki/Beta-Propiolactone

How is the COVAXIN like vaccines made?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202686/

Bharat Biotech, ICMR publish Covaxin Phase 1 data showing safe, enhanced immunity to Covid-19 disease
https://www.firstpost.com/india/bharat-biotech-icmr-publish-covaxin-phase-1-2-safety-data-in-an-interim-report-in-lancet-9229311.html

Press Information Bureau Government of India
https://pib.gov.in/PressReleseDetail.aspx?PRID=1685761

Regulatory approval of COVID-19 vaccine for restricted use in clinical trial mode
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00045-1/fulltext

India begins COVID-19 vaccination amid trial allegations
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00145-8/fulltext

Watch | 'Mistake to Authorise Covaxin Without Phase 3 Data': Dr Ashish Jha
https://thewire.in/health/mitali-mukherjee-ashish-jha-bharat-biotech-covaxin

Scientists Urge Govt to Release Covaxin Phase 3 Trial Data Before Rollout
https://science.thewire.in/health/bharat-biotech-covaxin-vaccine-data/

How COVAXIN works?
https://www.nytimes.com/interactive/2021/health/bharat-biotech-covid-19-vaccine.html

Sinopharm Vaccine

Inactivated virus based vaccine.
More than a million doses were administered by November 2020
Capacity to deliver 1 billion doses in 2021
Does not need cold-chain storage
Approved by UAE, Bahrain, Pakistan, and China
Two jabs needed. Almost 20 days apart.

Bloomberg vaccine tracker
https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/

BBIBP-CorV is the vaccine by Sinopharm. A state owned vaccine company from China.
https://en.wikipedia.org/wiki/BBIBP-CorV

Getting the two jabs
https://fortune.com/2021/02/05/sinopharm-covid-vaccine-china-data-should-i-get-vaccinated/

Two dose regime lesser than $145
https://www.fiercepharma.com/vaccines/china-sinopharm-chief-narrows-down-covid-19-vaccine-price-to-within-145-for-2-dose-regimen

Vaccine Efficacy is 79.34% according to the company
http://www.sinopharm.com/en/s/1395-4173-38923.html
http://www.sinopharm.com/1156.html
https://www.bbc.com/news/world-asia-china-55212787
http://www.pmlive.com/pharma_news/sinopharms_covid-19_vaccine_scores_approval_in_china_1360725

Pakistan approves Sinopharm vaccine in addition to AstraZeneca and Sputnik V
https://www.reuters.com/article/us-health-coronavirus-pakistan-vaccine/pakistan-approves-russias-sputnik-v-covid-19-vaccine-for-emergency-use-idUSKBN2A90WE

Does not need cold chain storage
https://fortune.com/2020/12/30/chinese-drugmaker-sinopharm-covid-vaccine-79-effective/

Looking beyond COVID-19 vaccine phase 3 trials
https://www.nature.com/articles/s41591-021-01230-y

Vaccination Results From Israel

How to pronounce Israel?
https://www.youtube.com/watch?v=m9mrJIiHOb4&ab_channel=Instinct-IntegratedIsraeliCombatives

Vaccination started on Dec 20th 2020
More than a million people have received both shots.
More than 2.6 million people have received one shot.
After the high risk folks, Israel is now administering vaccine to over 40 and high school students to enable them to go back to school.
Military reserves are helping with the rollout.

Results are biased because the people receiving the vaccine are already more careful of their risk and better informed.

Israel is leading the world in vaccination
Population of Israel is about 9.3 millions (reference: https://en.wikipedia.org/wiki/Demographics_of_Israel)
Israel has administered 3.9 million doses. (More than 40% of the population.)
42.92 doses for each 100 people. Best in the world so far.
More than 75% of its older population is now vaccinated at least with one dose.

Israel’s COVID situation
https://www.worldometers.info/coronavirus/country/israel/
613,578 cases
4,512 deaths

Wave three is going on. Strict lock downs are in effect.

Israel signed a contract with Pfizer to provide vaccination data in return for an early and a steady supply of the vaccine doses.
Here is the redacted version of this contract: https://govextra.gov.il/media/30806/11221-moh-pfizer-collaboration-agreement-redacted.pdf

Preliminary findings: 
Over 12,000 people test positive for COVID-19 after receiving Pfizer vaccine
https://www.wionews.com/world/israel-over-12000-people-test-positive-for-covid-19-after-receiving-pfizer-vaccine-358242

Initial data by Clalit (Israel’s largest health fund.)
200,000 people 60+ administered the first dose.
14-18 days after the first dose, partially vaccinated were 33% less likely to be infected compared to the similar cohort that are not vaccinated.

Maccabi’s research arm data
430,000 people’s data
13-21 days after the first shot 60% reduction in infections.
For 50,777 people vaccinated
On day 23rd (two days after the second shot,) 60% drop in hospitalizations.

On Monday (Jan 25th 2021) Israeli health ministry and Maccabi released new data.
Out of 428,000 people vaccinated
A week after only 63 people (0.014%) were infected.
Out of 128,000 people that are vaccinated.
A week after only 20 people (0.01%) were infected.

References:
Bloomberg vaccine tracker
https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/

Israel COVID metrics
https://www.worldometers.info/coronavirus/country/israel/

Twitter thread from Dr. Ran Balicer
https://twitter.com/RanBalicer/status/1352572121298436100

Pfizer vaccine doing great in Israel
https://www.nytimes.com/2021/01/25/world/middleeast/israels-vaccine-data.html

Vaccines are thought to continue to protect against the new variants (as of Jan 26th 2021)
https://www.nytimes.com/2021/01/25/health/coronavirus-moderna-vaccine-variant.html

BMJ on Israel’s vaccine data
https://www.bmj.com/content/372/bmj.n217

60% drop in hospitalizations in vaccinated folks
https://www.timesofisrael.com/israel-sees-60-drop-in-hospitalizations-for-over-60s-in-weeks-after-vaccination/

Promising results from the vaccination drive in Israel
https://www.seattletimes.com/nation-world/world/israeli-studies-show-promising-results-from-vaccination-drive/

Johnson and Johnson Vaccine - Pandemic Will Be Over Soon

How does J&J vaccine work?
https://youtu.be/n_uTPwA37C0

DrBeen Video on the phase I and II trials
https://youtu.be/zdX8TCR89kQ

Phase III interim analysis
https://www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial

NIH on the interim analysis
https://www.nih.gov/news-events/news-releases/janssen-investigational-covid-19-vaccine-interim-analysis-phase-3-clinical-data-released

Sputnik Vaccine is 91.6% Effective

Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00234-8/fulltext

Sputnik V COVID-19 vaccine candidate appears safe and effective
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00191-4/fulltext

About this vaccine
https://sputnikvaccine.com/about-vaccine/

Wikipedia article
https://en.wikipedia.org/wiki/Sputnik_V_COVID-19_vaccine

Testicular Damage and Infertility with COVID?

Immune privilege of the testicular tissue
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197207/

Assessment of SARS-CoV-2 in human semen—a cohort study
https://www.fertstert.org/article/S0015-0282(20)30519-7/fulltext

Testicular pain as an unusual presentation of COVID-19: a brief review of SARS-CoV-2 and the testis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377719/

No evidence of severe acute respiratory syndrome–coronavirus 2 in semen of males recovering from coronavirus disease 2019
https://www.fertstert.org/article/S0015-0282(20)30384-8/fulltext

A coronavirus disease 2019 (COVID-19) patient with bilateral orchitis: A case report
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449893/

Interferon Beta- A New Study

Excerpt from Wikipedia
Interferons (IFNs, /ˌɪntərˈfɪərɒn/[1]) are a group of signaling proteins[2] made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

A small study shows good results with interferon beta 1
https://www.sciencemediacentre.org/expert-reaction-to-announcement-by-synairgen-that-their-drug-sng001-has-had-positive-results-in-initial-trials-on-covid-19-patients/

Trial for the interferon beta
https://clinicaltrials.gov/ct2/show/NCT04385095

Interferons
https://en.wikipedia.org/wiki/Interferon#:~:text=Interferons%20(IFNs%2C%20%2F%CB%8C%C9%AA,heighten%20their%20anti%2Dviral%20defenses.

Interferon Beta
https://en.wikipedia.org/wiki/Interferon_type_I#IFN-.CE.B2

An invitro study on SARS-COV-1 (not 2)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322919/

AstraZeneca Vaccine Efficacy Update

AstraZeneca’s original trial results are here. Let’s check their latest updates, especially, for the vaccine efficacy.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

COVID-19 Vaccine AstraZeneca confirms 100% protection against severe disease, hospitalisation and death in the primary analysis of Phase III trials
https://www.astrazeneca.com/media-centre/press-releases/2021/covid-19-vaccine-astrazeneca-confirms-protection-against-severe-disease-hospitalisation-and-death-in-the-primary-analysis-of-phase-iii-trials.html

DrBeen’s AstraZeneca vaccine videos

AstraZeneca Vaccine is 62% and 90% Effective
https://youtu.be/tDpSbYUZos8

AstraZeneca and our nucleus
https://youtu.be/wYz-7zB_AAw

How Is AstraZeneca Vaccine Made?
https://youtu.be/C_kzjxQfAJo

Is There Fetal Tissue In AstraZeneca Vaccine?
https://youtu.be/vWMWM4YyS6M

A Koolbeen’s message about the AstraZeneca efficacy:
“Don Phelps  • 2 hours ago 
Dear Dr, There has been published recent update on AstroZenica vac.
The different efficacy rates turned out to be due to time interval between first and second shot, and delay period before efficacy measured.  I belive I saw it WhiteBoard Doctor.  But I also watch TrialSiteNews and medcram. So please update your review. Hope that is helpful.  I do love and appreciate you and this channel. Yours, Don”

Oxford’s article
https://www.ox.ac.uk/news/2021-02-02-oxford-coronavirus-vaccine-shows-sustained-protection-76-during-3-month-interval

Latest paper from AstraZeneca
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268

All news for AstraZeneca vaccine
https://www.research.ox.ac.uk/Area/Search/vaccine_development

Is It Safe to Delay a Second COVID Vaccine Dose?
https://www.scientificamerican.com/article/is-it-safe-to-delay-a-second-covid-vaccine-dose/

After Admitting Mistake, AstraZeneca Faces Difficult Questions About Its Vaccine
https://www.nytimes.com/2020/11/25/business/coronavirus-vaccine-astrazeneca-oxford.html

A good table for various vaccines here:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00306-8/fulltext

Why did a German newspaper insist the Oxford AstraZeneca vaccine was inefficacious for older people—without evidence?
https://www.bmj.com/content/372/bmj.n414

Something of interesting. Vaccine mixtures are being tested as well.
https://www.research.ox.ac.uk/Article/2021-02-04-oxford-leads-first-trial-investigating-dosing-with-alternating-vaccines
https://www.research.ox.ac.uk/Article/2020-12-08-first-peer-reviewed-results-phase-3-coronavirus-vaccine
https://www.research.ox.ac.uk/Article/2020-12-08-phase-3-trial-data-publication-faq
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00306-8/fulltext

#drbeen #koolbeens #COVID

Errata: I said vitamin C in the beginning, it should have been vitamin D.

New Study from Barcelona Spain finds that Vitamin D could reduce the risk of COVID deaths by 60%

Here is a vitamin D study from Barcelona. With, great results. Takeaway is that the baseline levels of vitamin D should be correct in all of us. It improves our chances of survival and could reduce the risk of severe disease and death by 60%. 

Also, soon at the admission in a hospital correcting the vitamin D levels is crucial. Authors found that the vitamin D levels corrected in the ICU did not have a large impact compared to the levels corrected earlier in the wards.
However, there are certain limitations of the study that are reducing its impact. 

Some limitations:
It is not really an RCT. Instead it is some sort of possibly random cluster trial. 
Study seems to change protocol of the Vitamin D administration.
Study is not in the study registry for some reason. 
Authors say that it is an observational open randomized trial. While they write it as an RCT.
Still the results are in line with the way vitamin D’s effect should be.

A critique and discussion of the study’s limitations
https://twitter.com/fperrywilson/status/1360944814271979523

Author’s response
https://pubpeer.com/publications/DAF3DFA9C4DE6D1B7047E91B1766F0#11

A review of the Vitamin D studies. Check the comments.
https://jamanetwork.com/journals/jama/fullarticle/2775003

Vitamin D levels and sources
https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

Vitamin D levels for various illnesses
https://www.pdr.net/drug-summary/Ergocalciferol-ergocalciferol-24306

Vitamin D levels conversion
https://www.vitamaniathemovie.com/vitamin-d-levels/

A study finds the correct levels of vitamin D
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541280/

DrBeen’s Vitamin D Mechanism Video
https://youtu.be/wJyT1YSwe-8

Immune system modulation
https://youtu.be/wJyT1YSwe-8?t=1379

DrBeen’s Vitamin D High Dose Study
https://youtu.be/3mth0LqC9z4

Why vitamin D doesn’t work correctly in polluted environments?
https://youtu.be/hLCNCiznK0Q

Studies showing Vitamin C and D function
https://youtu.be/6AlRKmbtYUI

What Vitamin D Level Reduces The Risk of Death From COVID-19? A New Study From Boston University
https://youtu.be/upqAME1_G6U

Colchicine Reduces COVID Intensity and Deaths

How does it work?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656054/

Colchicine Study
Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19
https://www.medrxiv.org/content/10.1101/2021.01.26.21250494v1

Colchicine Study
Beneficial effects of colchicine for moderate to severe COVID-19: a randomized, double-blinded, placebo-controlled clinical trial
https://rmdopen.bmj.com/content/7/1/e001455

COVID Long Hauler (Symptoms and Management)

Possible causes
Is it because of the persistent virus or slow clearance of it?
Is it because of the immune cell mutation?
Is it because of autoimmune response due to molecular mimicry?
Is it because of other viruses reactivating e.g. EBV which in turn can cause fatigue.
Is it a blood flow issues to brain?
Is it an infection of the brain tissue?
Is it the damage to the endothelium of the blood vessels? (Difference in sex shows that the issue is more common in women which also aligns with more immune system issues in women, hence, it is possibly the immune system vs., endothelial damage.)

A registry for long haulers
https://youandmeregistry.com/about/

Leronlimab study
https://clinicaltrials.gov/ct2/show/NCT04678830

CCR5 receptor function is to help promote immune cell chemotaxis. It is also a receptor for the HIV virus.
https://en.wikipedia.org/wiki/CCR5

What is the problem (symptoms?)
More than 200 symptoms
Most common are the following
Fatigue
Body aches
Breathing issues
Brain fog/Cognitive impairment (similar to myalgic encephalomyelitis/chronic fatigue syndrome ME/CFS)
Cough
Chills
Sweat
Headache
GIT issues

References for symptoms
https://jamanetwork.com/journals/jama/fullarticle/2771111
https://greatist.com/health/covid-long-haulers-symptoms#what-a-day-feels-like
https://www.medrxiv.org/content/10.1101/2020.12.24.20248802v2
https://www.medrxiv.org/content/10.1101/2020.12.24.20248802v2.full.pdf

What is the tragedy?
Psychosomaticizing of the problem by physicians.
Outright ignoring it.
Not knowing how to approach it even when they empathize with the patient’s symptoms.

Harvard’s article
https://www.health.harvard.edu/blog/the-tragedy-of-the-post-covid-long-haulers-2020101521173

A good article to read
https://jamanetwork.com/journals/jama/fullarticle/2771111

How large is the problem?
More than 30% of the COVID patients.
Not necessarily only severe cases.
UK study says about 10%

Brain fog
Fluvoxamine, glymphatic massage, neck and spine pumping.

An important site to keep in mind for long haulers (long hauler science tracker)
https://www.c19recoveryawareness.com/research

Dr. Patterson and Dr. Yo paper
https://www.biorxiv.org/content/10.1101/2020.12.16.423122v1

Important points:
LH can result from mild infection as well. Hence, LH is not a consequence of the severe COVID only. That means labs for severe cases cannot represent accurately the LH consequence.

IL6, IL8, TNF-alpha are persistently high. They cycle.

Dr. Patterson
VEGF elevated in 79% of LH, burning sensation, neuropathy, numbness, tingling, weakness, brain fog.
Maraviroc decreases VEGF - helping with brain fog. Plus brings RANTES and IL6 down.
Triad: Ivermectin, Maraviroc, and low dose steroids are showing improvement (85%-90% are responding.)

Listen to Dr. Patterson and Dr. Yo for long hauler severity index
https://www.pscp.tv/w/1YqxoyWBjEBGv

CD8 cell count is very low - single digits. 2-7% normal is 30%. Almost as immunosuppressed as HIV.
Low CD8 count means detectable virus for 87 days
25% LHs have low CD8%.

CCR5 - allows cells to reach the area of inflammation. Maybe a delta 32 deletion causes protection against severe COVID. It is for the CCR5. It is possible that lower CCR5 receptors in heterozygous patients keeps the immune response to a lower level, while homozygous people for the CCR5 receptors have a higher number of CCR5 receptors responding more to RANTES, which in turn causes an overwhelming response to SARS-COV-2.

Maraviroc
https://en.wikipedia.org/wiki/Maraviroc

COVID Long Haulers Mast Cells (Mast Cell Activation Syndrome - MCAS) Part - 2

Prevalence of the MCAS
Pathophysiology of the MCAS
Possible Solutions
Connection of the MCAS with COVID

Low dose Naltraxone therapy for POTS and MCAS
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778345/

MCAS diagnosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753019/

Major and minor criteria for MCAS and Mastocytosis
https://www.researchgate.net/figure/Criteria-proposed-to-define-mast-cell-activation-disease-for-references-see-text_tbl2_50592316
https://www.wjgnet.com/2218-6204/full/v3/i1/1.htm

Study: Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529115/

What are good mast cell stabilizers?
https://www.bmj.com/content/370/bmj.m2722/rr-3

Study, Mast cells and COVID 19
Potential association of mast cells with coronavirus disease 2019
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644430/

COVID-19, Mast Cells, Cytokine Storm, Psychological Stress, and Neuroinflammation
https://journals.sagepub.com/doi/full/10.1177/1073858420941476

COVID Long Haulers Mast Cells (Mast Cell Activation Syndrome - MCAS) Part - 2

Prevalence of the MCAS
Pathophysiology of the MCAS
Possible Solutions
Connection of the MCAS with COVID

Low dose Naltraxone therapy for POTS and MCAS
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778345/

MCAS diagnosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753019/

Major and minor criteria for MCAS and Mastocytosis
https://www.researchgate.net/figure/Criteria-proposed-to-define-mast-cell-activation-disease-for-references-see-text_tbl2_50592316
https://www.wjgnet.com/2218-6204/full/v3/i1/1.htm

Study: Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529115/

What are good mast cell stabilizers?
https://www.bmj.com/content/370/bmj.m2722/rr-3

Study, Mast cells and COVID 19
Potential association of mast cells with coronavirus disease 2019
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644430/

COVID-19, Mast Cells, Cytokine Storm, Psychological Stress, and Neuroinflammation
https://journals.sagepub.com/doi/full/10.1177/1073858420941476

Will Ivermectin Block a Vaccine?

A very common question asked is, if Ivermectin will block the effect of a vaccine? 
We will discuss the vaccine’s lifecycle in our body and if the Ivermectin’s presence cause any issues?
We will also discuss Virus’ lifecycle and see how Ivermectin works there.
We will also compare and contrast the effect of the Ivermectin for a vaccine and the virus (SARS-COV-2)

Doctors Prescribing Ivermectin

Let’s talk about Ivermectin.
No affiliation with the following doctors. Sharing out of an intent to help.

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https://www.exstnc.com/

https://www.thecompleteguidetohealth.com/united-states-doctor-directory.html

https://covid19criticalcare.com/i-mask-prophylaxis-treatment-protocol/take-action-and-share-the-infos-with-your-doctor/#ivdoctors

https://myfreedoctor.com/

How is AstraZeenca's COVID vaccine made?
DrBeen's series on coronavirus vaccines explained. In this brief review we will check out the production steps of the AstraZeneca vaccine.

AstraZeneca (Oxford college’s partner) has released the interim results for the trials conducting in the UK and Brazil.

https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html

Safety data study
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext

Ivermectin Still Effective Against Variants?

Let’s discuss if the action of ivermectin on SARS-COV-2 is reduced on its variants.

Great article about various variants
https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html#B1526

We will discuss the important mutations in the following variants of the SARS-COV-2.
UK Variant (B.1.1.7)
South Africa Variant (B.1.351)
Brazil Variant (P.1)
California Variant (B.1.427, B.1.429)
NY Variant (B.1.526)

CDC on variants
https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html
https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance.html

NPR or variants
https://www.npr.org/sections/health-shots/2021/03/03/971327204/worried-about-coronavirus-variants-heres-what-you-need-to-know

Variant trackers
https://cov-lineages.org/lineages/lineage_B.1.html
https://nextstrain.org/ncov/global

Johnson and Johnson Vaccine Efficacy (Approval Data)

Johnson and Johnson’s single shot vaccine is approved by FDA. Let’s review its safety and efficacy data as published by FDA.

Vaccines and Related Biological Products Advisory Committee Meeting February 26, 2021 
https://www.fda.gov/media/146217/download

FDA Issues Emergency Use Authorization for Third COVID-19 Vaccine
https://www.fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-third-covid-19-vaccine

FACT SHEET FOR HEALTHCARE PROVIDERS ADMINISTERING VACCINE (VACCINATION PROVIDERS)
https://www.fda.gov/media/146304/download

FACT SHEET FOR RECIPIENTS AND CAREGIVERS
https://www.fda.gov/media/146305/download

Johnson & Johnson COVID-19 Vaccine Authorized by U.S. FDA For Emergency Use - First Single-Shot Vaccine in Fight Against Global Pandemic
https://www.jnj.com/johnson-johnson-covid-19-vaccine-authorized-by-u-s-fda-for-emergency-usefirst-single-shot-vaccine-in-fight-against-global-pandemic

Johnson & Johnson Announces Submission of European Conditional Marketing Authorisation Application to the EMA for its Investigational Single-Shot Janssen COVID-19 Vaccine Candidate
https://www.jnj.com/johnson-johnson-announces-submission-of-european-conditional-marketing-authorisation-application-to-the-ema-for-its-investigational-single-shot-janssen-covid-19-vaccine-candidate

Johnson & Johnson Single-Shot COVID-19 Vaccine Candidate Unanimously Recommended for Emergency Use Authorization by U.S. FDA Advisory Committee
https://www.jnj.com/johnson-johnson-single-shot-covid-19-vaccine-candidate-unanimously-recommended-for-emergency-use-authorization-by-u-s-fda-advisory-committee

High Dose Ivermectin

Dr. David E., Scheim hypothesizes that the COVID related hypercoagulability is due to the CD147 proteins on the RBCs attaching with SARS-COV-2 spike proteins. He proposes that Ivermectin binds with the spike proteins of the SARS-COV-2 hence, preventing the spike protein binding to the CD147 and RBC clumping.

We will learn the following
CD147 and its presence on RBC
CD147 and its variation for various blood groups
Ivermectin’s binding with CD147
Dose of Ivermectin suitable for this binding
Malarial parasite and CC147
Clumping of the RBCs and hypercoagulable state in COVID

Hypothesis By Dr. David E., Scheim
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3636557

PDF
https://poseidon01.ssrn.com/delivery.php?ID=011106009067119120098004115115105024038039000065003034103087110087095096085122070078010118005034010099113066110023007082124124039035093009046115074127092031083107025086069046115065064088115105001026124090001081027031088122091064020114072103067025096066&EXT=pdf&INDEX=TRUE

CD147
https://en.wikipedia.org/wiki/Basigin

CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement
https://link.springer.com/article/10.1007/s12015-020-09976-7

Plasmodium falciparum
https://en.wikipedia.org/wiki/Plasmodium_falciparum

More Deaths By The UK Variant - (Was I Wrong All This Time?)

A study from UK finds that the UK variant B.1.1.7 (VOC202012/1) is more contagious and more deadly than the wild type SARS-COV-2. Let’s review this study.

The Study
Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study
https://www.bmj.com/content/372/bmj.n579​

A good article on the UK variant
https://www.nytimes.com/2021/02/13/wo...​

Another Study
Increased hazard of death in community-tested cases of SARS-CoV-2 Variant of Concern 202012/01
https://www.medrxiv.org/content/10.11...​

DrBeen’s video about the variant of concern
https://youtu.be/7EAGMu_UmF4​
https://youtu.be/vp-Ak7w3QE0​

Novavax Phase III and Phase IIb Trial Results (Why Do I Like Novavax?)

Novavax COVID-19 vaccine results for phase III in the UK and the phase 2b in South Africa are published. Data is still not available. Let’s review the results here.

DrBeen explains Novavax Technology (one beautiful technology it is.)
https://youtu.be/Q00lyd3gyy4

Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 Trial
https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3

Phase 3 trial of Novavax investigational COVID-19 vaccine opens
https://www.nih.gov/news-events/news-releases/phase-3-trial-novavax-investigational-covid-19-vaccine-opens

Novavax Recombinant Particle Technology
https://www.novavax.com/our-unique-technology#recombinant-nanoparticle-vaccine-technology

Good articles about Novavax
https://qz.com/1950365/what-is-the-novavax-vaccine-and-how-does-it-work/
https://www.genengnews.com/news/the-cold-truth-about-covid-19-vaccines

Current state of vaccination (on March 15th 2021)
Vaccine tracker
https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/

Cases in Israel
https://www.worldometers.info/coronavirus/country/israel/
https://ourworldindata.org/grapher/israel-covid-19-cases-by-age
https://theconversation.com/coronavirus-is-the-kent-variant-responsible-for-the-rise-in-cases-among-young-people-in-israel-and-italy-155103

Cases in Brazil
https://www.worldometers.info/coronavirus/country/brazil/

Cases in South Africa
https://www.worldometers.info/coronavirus/country/south-africa/

Cases in the USA
https://www.worldometers.info/coronavirus/country/us/

Cases in UKhttps://www.worldometers.info/coronavirus/country/uk/

Nasal Spray for Virus/SARS-COV-2 Reduction

A Canadian company has successfully run trials and tests to show that nitric oxide based nasal spray can reduce viral replication by 99.99% in 72 hours. Let’s look at this spray, the test results, and its mechanism of action for viruses.

Pre-read/watch
DrBeen’s discussion about N-AcetylCysteine
https://youtu.be/K8kKWgsGIU8

About Cysteine and Cystine
https://www.sciencedirect.com/topics/chemistry/sulfur-containing-amino-acid

saNotize nasal spray site.
https://sanotize.com/covid-19/

About NO
https://sanotize.com/why-nitric-oxide/

About neuraminidase inhibitors
https://en.wikipedia.org/wiki/Neuraminidase_inhibitor

About neuraminidase
https://en.wikipedia.org/wiki/Neuraminidase

About NO from Goodman Gillman for reference
Platelet activation and coagulation do not normally occur within an intact blood vessel. Thrombosis is prevented by several regulatory mechanisms that require healthy vascular endothelium. Nitric oxide and prostacyclin synthesized by endothelial cells inhibit platelet activation

Produced by activated helper T (TH) and natural killer (NK) cells, IFN-γ enhances the microbicidal activity of macrophages by inducing mammalian inducible nitric oxide synthase (iNOS, also called NOS2), thereby increasing their production of nitric oxide (NO) and their capacity to kill intracellular pathogens.

Brunton, Laurence; Knollman, Bjorn; Hilal-Dandan, Randa. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition (Goodman and Gilman"S the Pharmacological Basis of Therapeutics) . McGraw-Hill Education. Kindle Edition. 

Merck’s Molnupiravir (EIDD-281) Effective Against SARS-COV-2

Molnupiravir is a nucleoside analog. It has shown to be able to cause mutations accumulation and the RNA replication errors during the virus replication in vitro and in mouse models (in-vivo).

Let’s look at the following
What is Molnupiravir?
What is EIDD-281?
What is a nucleoside and a nucleotide?
How is positive mRNA is replicated to a negative sense RNA and back again during the viral replication?
How does EIDD-281 disrupt this process?
Why is it better performing than Remdesivir?
It’s therapeutic dose is non cytotoxic.
Concerns about its toxicity in humans.

References
https://stm.sciencemag.org/content/12/541/eabb5883
https://en.wikipedia.org/wiki/Molnupiravir
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848974/
https://en.wikipedia.org/wiki/Nucleoside
https://en.wikipedia.org/wiki/Nucleotide
https://www.reuters.com/article/us-health-coronavirus-merck-co/merck-says-study-shows-covid-19-drug-causes-quick-reduction-in-virus-idUSKBN2AY07U
https://clinicaltrials.gov/ct2/show/NCT04405739

Death, Anaphylaxis, And Other Vaccine Adverse Effects (March 16th 2021 - USA)

Errate: note I did not filter correctly for deaths. These numbers are incorrect.

#koolbeens have been asking to track vaccine administration related adverse effects/reaction and report on them. We will go over various adverse reactions in today’s discussion. We will go over various side effects in the Vaccine Adverse Effects Reporting System (VAERS) reporting system.

CDC posts this note at the bottom of each report:
Note: Submitting a report to VAERS does not mean that healthcare personnel or the vaccine caused or contributed to the adverse event (possible side effect).

Tracker by CDC
https://wonder.cdc.gov/vaers.html

We will look into the following adverse reactions.
1. Pain
2. Redness
3. Fatique
4. Fever
5. Skin irritation
6. Fainting
7. Facial droop
8. Anaphylaxis
9. Allergic reactions
10. Eyesight effects
11. Tremors
12. Inability to move
13. Death

References
Statista on vaccine efficacy
https://www.statista.com/chart/23510/estimated-effectiveness-of-covid-19-vaccine-candidates/

Bloomberg vaccine tracker
https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/

CDC about moderna
https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/index.html
CDC about Pfizer/BioNTech
https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/index.html
CDC about Janssen
https://www.cdc.gov/vaccines/covid-19/info-by-product/janssen/index.html
Moderna press releases
https://investors.modernatx.com/news-releases

Vaccine news
https://www.ajmc.com/view/a-timeline-of-covid-19-vaccine-developments-in-2021

https://fortune.com/2021/03/10/covid-vaccine-pfizer-moderna-johnson-johnson-numbers-by-state-coronavirus-vaccines-shots-doses-given-us-latest-update/

COVID-19 Symptoms in Kids

Children are fortunately better protected from COVID. Hospitalization and mortality is also significantly low in children. However, understanding and recognizing the signs and symptoms of COVID in children is important for parents and the emergency doctors. It is also important to recognize when to take a child to emergency. We will discuss these topics in this session.

CDC 
https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/symptoms.html

CDC for Pediatric healthcare providers
https://www.cdc.gov/coronavirus/2019-ncov/hcp/pediatric-hcp.html

John Hopkins on symptoms in children
https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/coronavirus-in-babies-and-children

American Academy of Pediatrics
https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/

Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-in-babies-and-children/art-20484405

BBC Article about the COVID deaths in babies in Brazil.
Why are so many babies dying of Covid-19 in Brazil?
https://www.bbc.com/news/world-latin-america-56696907

UK study showing no evidence of increased infection rate or death rates in children
https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00030-4/fulltext
PDF: https://www.thelancet.com/action/showPdf?pii=S2352-4642%2821%2900030-4

Vaccine Induced Clotting - How Will A Doctor Manage It?

About six million doses administered. 6 women developed clotting. 1 died. 1 hospitalized in critical condition. Clots develop between 1 week to 3 weeks.

FDA and CDC Statement
https://www.cdc.gov/media/releases/2021/s0413-JJ-vaccine.html

A German study provided a good working model for this situation, but, associated with AstraZeneca
Study for AstraZeneca showing a possible relation of thrombotic thrombocytopenia to the vaccine. FDA and CDC suspect a similar relation to Janssen vaccine.
https://www.researchsquare.com/article/rs-362354/v1

Note: this is not medical advice or a prescription. The following information here and in the video that goes with this is for educational purposes only.
Don’t take any medicine without your doctor’s advice. These medicines can lead to death.

General clinical signs and symptoms
Persistent headache (severe,) shortness of breath, leg pain, nose bleed, GIT pain, petechial hemorrhages under the skin, bruising under the skin, etc.
Thrombocytopenia within 5-10 days. 
Platelet count dropping to 50% or more.
4T score: https://qxmd.com/calculate/calculator_113/hit-4t-s-score

Management
Management should start as soon as the diagnosis is suspected before the results from the labs are available.

Outdoor possible management. 
Note, these patients must be referred to ICU/or call 911. Any wasted time can cause permanent damage.
Possible outdoor/supportive management as recommended by Prof., Greinacher et., al
Oral: Rivaroxaban, Apixaban, high dose IVIG

In Hospital and ICU
Direct thrombin inhibitors for prophylaxis and management
Argatroban IV is more important and urgent than the oral agents. Move to ICU.
Transition to warfarin or other anticoagulants (not Heparin) for 30 days when platelet count has recovered. 

Labs
Normal platelet count is 150,000 to 450,000 per microliter of the blood.
Reference: healthy platelet count https://www.hopkinsmedicine.org/health/conditions-and-diseases/what-are-platelets-and-why-are-they-important
Enzyme immunoassay for heparin-induced thrombocytopenia/thrombosis are widely available
Platelet activation assays from the labs
Perform doppler of the lower extremities to rule out any thrombi in the legs
Get aPTT fort iterating argatroban
aPTT = activated partial thromboplastin time.

Reference for the platelet aggregation test molecular mechanisms
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578190/
Rivaroxaban https://en.wikipedia.org/wiki/Rivaroxaban
Apixaban https://en.wikipedia.org/wiki/Apixaban
Argatroban https://en.wikipedia.org/wiki/Argatroban
Aspirin https://en.wikipedia.org/wiki/Aspirin
Rivaroxaban vs., Aspirin http://www.pmlive.com/pharma_news/xarelto_no_better_than_aspirin_in_secondary_stroke_study_1207165
DrBeen video on Aspirin https://youtu.be/o9CvTz6XS4A

Reference book:
Papadakis, Maxine A.; McPhee, Stephen J.; Rabow, Michael W.. CURRENT Medical Diagnosis and Treatment 2016 (LANGE CURRENT Series) . McGraw-Hill Education. Kindle Edition. 

Vaccine After COVID (A Study)

Today we will discuss a study that shows the results of administering one or two doses of Moderna or Pfizer vaccine to a previously COVID infected person.

Link to the study we are reviewing today
https://www.nejm.org/doi/full/10.1056/NEJMc2101667

You might be thinking, what are the protective levels? Link below gives some answers.
What antibody levels are found in outpatient, convalescent plasma donors, hospitalized, and critical patients?
https://www.nature.com/articles/s42003-021-01649-6

A longitudinal study showing the antibody titer changes in patients with varying COVID severity.
https://academic.oup.com/jid/article/223/2/197/5916372

This diagram is important
https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jid/223/2/10.1093_infdis_jiaa618/3/jiaa618_fig2.jpeg?Expires=1621032769&Signature=gk9BQdy8Eb85bIp4IaK7ns5FqUu8IV4QvXmCF7I1d6wAphskY1KvHiutetQYa5aMiyZuuFSpl0r5tMQBvKclC1XPJFhZ0jxPCBjPAH3-BSuhUmnWOoiY9OqU-145XUu6eBWZdUfX7j9GVqdL2V3VV7OsHfEo9AWwx8WGS8qFjITryBRy4tteStqxU8Wns77Q9bpBBk38xQDnVqH9Ywivwaxnb8~uq0wrAgQ2sqzOwI5yKIS9-PKkb2yg4xmn0m6GtN0fEKvshXYRIU-OBaUSilyeP0AeQ5yB05w7xHMhtg6zGE1LNSvNIcCZdoTqJ5~aD5ygYQNCYozOBGbNfFn~6g__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA

Effective virus-neutralizing activities in antisera from the first wave of survivors of severe COVID-19
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934937/

One more study for the antibody titers https://www.cell.com/immunity/pdfExtended/S1074-7613(20)30445-3

https://www.cell.com/cell/pdf/S0092-8674(20)31685-8.pdf

Scientists Develop a New Vaccine To Fight All Mutants and Strains of Coronaviruses

US Researchers have built and tested a super-vaccine that helps immune system attack all coronaviruses regardless of their variations and mutations. Let’s see the vaccine, its mechanism of action, and the results of the testing done on pigs.

The research pre-print in Proceedings of the National Academy of Sciences of the Unites States of America (PNAS)
https://www.pnas.org/content/118/18/e2025622118

An article with a good summary
https://weather.com/en-IN/india/coronavirus/news/2021-04-21-scientists-invent-new-vaccine-that-can-fight-all-coronaviruses

Super Vaccine For Coronaviruses - More Updates

Yesterday’s discussion about the possible super vaccine to coronaviruses generated a lot of good discussion and important questions. Let’s discuss these questions before moving on to other topics.

The research pre-print in Proceedings of the National Academy of Sciences of the Unites States of America (PNAS)
https://www.pnas.org/content/118/18/e2025622118

An article with a good summary
https://weather.com/en-IN/india/coronavirus/news/2021-04-21-scientists-invent-new-vaccine-that-can-fight-all-coronaviruses

Israel Pfizer Vaccine Efficacy At A Large Scale

A study and a statement from Israel health systems have shown the efficacy of the Pfizer vaccine when measured in a large cohort. The data we will discuss is obtained from 1.4 million in one case and about 1.2 million in the other case. Generally, the vaccine efficacy is similar or better than observed during the trial. Let’s review this data.

Study
BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting
https://www.nejm.org/doi/full/10.1056/NEJMoa2101765?query=featured_home

A summary for the above study
First large-scale peer-reviewed study of real-world effectiveness of COVID-19 vaccine by Israel’s Clalit Research Institute published in The New England Journal of Medicine
http://clalitresearch.org/first-large-scale-peer-reviewed-study-of-real-world-effectiveness-of-covid-19-vaccine-by-israels-clalit-research-institute-published-in-the-new-england-journal-of-medicine/

7 days after the second dose
https://translate.google.com/translate?sl=auto&tl=en&u=https://www.ynet.co.il/health/article/H1bfecCLO%23autoplay

Risk difference calculation
https://sphweb.bumc.bu.edu/otlt/MPH-Modules/EP/EP713_Association/EP713_Association5.html

Pfizer Vaccine Associated Adverse Effects From Israel

Today we have a special guest David. David is helping us walk-through the Hebrew version of the vaccine adverse effects data from Israel. Get your questions ready, and let’s discuss.

Link to the adverse events data deck: https://www.gov.il/BlobFolder/reports/vaccine-efficacy-safety-follow-up-committee/he/files_publications_corona_side-effects-after-vaccination-01032021.pdf

Risk Of Clotting By COVID-19 Higher Than For Vaccines - Oxford Study

Oxford study has claimed that the review of data shows a 39/million cerebral venous thrombosis (CVT) vs., 5/million by Astra Zeneca, and 4/million by mRNA vaccines. Let’s review the data presented.

Risk of rare blood clotting higher for COVID-19 than for vaccines
https://www.ox.ac.uk/news/2021-04-15-risk-rare-blood-clotting-higher-covid-19-vaccines

PDF
https://osf.io/a9jdq/

Thrombocytopenia case
https://www.nejm.org/doi/full/10.1056/NEJMc2105869

Zoom link for today's talk:  https://us02web.zoom.us/j/87500231322

New Technique To Study COVID Pathology (High Parameter Imaging Mass Cytometry)

What Is The Difference Between A Bacterial Infection And A Viral Infection In Kingston, New York?
 What Is The Difference Between A Bacterial Infection And A Viral Infection In Kingston, New York? - John H. Fisher, P.C.

New technique provides detailed map of lung pathology in COVID-19
New technique provides detailed map of lung pathology in COVID-19 -- ScienceDaily

Method for Tagging Antibodies with Metals for Mass Cytometry Experiments
Method for Tagging Antibodies with Metals for Mass Cytometry Experiments - PubMed

Cytometry by time of flight
https://en.wikipedia.org/wiki/CyTOF

New High-Resolution Imaging Technology Reveals COVID-19 Lung Pathology in Space and Time
https://www.genengnews.com/news/new-high-resolution-imaging-technology-reveals-covid-19-lung-pathology-in-space-and-time/

Double Mutant Variant in India (B.1.617)

India’s spike in COVID cases is suspected of the double mutant. It is now the dominant strain in Maharashtra state (60%.) Let’s review the properties of this strain in terms of contagiousness/transmission, virulence/severity of disease, and vaccine/infection generate antibody efficacy.

India’s coronavirus surge is being driven by ‘double mutant variant’, making containment even harder
https://www.scmp.com/news/asia/south-asia/article/3129947/indias-coronavirus-surge-being-driven-double-mutant-variant

B.1.617 Lineage Report
https://outbreak.info/situation-reports?pango=B.1.617

References
https://www.aljazeera.com/news/2021/4/19/is-a-double-mutant-covid-variant-behind-indias-record-surge
http://www.xinhuanet.com/english/asiapacific/2021-04/17/c_139887351.htm
https://www.bbc.com/news/world-asia-india-56507988

India COVID cases
https://www.worldometers.info/coronavirus/country/india/
https://www.covid19india.org/
https://www.covid19india.org/state/MH
https://www.covid19india.org/state/UP

Administration of Second Dose Of Moderna Vaccine After An Immediate Hypersensitivity Reaction to The First Dose

Immunologist have reported administration of the second dose of Moderna vaccine in a graded fashion with protective antibody titers to the patients that had immediate hypersensitivity reaction to the first dose.

Link to the case reports
https://www.acpjournals.org/doi/10.7326/L21-0104

Azithromycin is an antibiotic used for the treatment of a number of bacterial infections.[3] This includes middle ear infections, strep throat, pneumonia, traveler's diarrhea, and certain other intestinal infections.[3] It can also be used for a number of sexually transmitted infections, including chlamydia and gonorrhea infections.[3] Along with other medications, it may also be used for malaria.[3] It can be taken by mouth or intravenously with doses once per day.[3]

https://en.wikipedia.org/wiki/Azithromycin

Macrolides

https://en.wikipedia.org/wiki/Macrolide#:~:text=The%20mechanism%20of%20action%20of,well%20as%20inhibiting%20ribosomal%20translation.

Effect of Azithromycin on NK cells

https://pubmed.ncbi.nlm.nih.gov/22410149/

A quick note about the steroid use earlier.

2004 study showing that the early treatment with steroids results in higher plasma load of the virus

https://pubmed.ncbi.nlm.nih.gov/15494274/

A study showing that early use of methylprednisolone (part of MATH+ as well) improved the clinical outcomes:

https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa601/5840526

A meta study showing the effect of the use of corticosteroids

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30317-2/fulltext

A meta study showing negative outcomes with corticosteroids

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195158/

Systemic steroids in patients with COVID-19: pros and contras, an endocrinological point of view

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279635/

Vaccines

Oxford RECOVERY trial showing dexamethasone is effective

https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf

Moderna Phase I trial results

https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

Pfizer coronavirus vaccine

https://www.pfizer.com/science/coronavirus/vaccine

PFIZER AND BIONTECH ANNOUNCE EARLY POSITIVE UPDATE FROM GERMAN PHASE 1/2 COVID-19 VACCINE STUDY, INCLUDING FIRST T CELL RESPONSE DATA

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-early-positive-update-german

Oxford Vaccine Update

https://www.bbc.com/news/uk-53469839

CansinoBIO with Ad5-nCov

http://www.cansinotech.com/homes/article/plist/45.html

Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext

CanSinvo vaccine is a modified adenovirus

https://www.reuters.com/article/us-health-coronavirus-cansinobio/cansino-covid-19-vaccine-shows-immune-response-in-human-trial-idUSKCN24L1NP

CoronaVac by Sinovac

https://www.precisionvaccinations.com/vaccines/coronavac-sars-cov-2-vaccine

http://www.sinovac.com/?optionid=754&auto_id=904

Important vaccines tracker

https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker

An opinion piece on the possible concerns about the vaccines:

https://www.statnews.com/2020/07/31/covid-19-vaccine-amazingly-close-why-am-i-so-worried/

Vitamin K Deficiency Leads to Poor COVID-19 Outcome 

https://youtu.be/hSbHkMb_FKI

Vitamin deficiency is linked to hypercoagulability and lung fibrosis.

The study

https://www.preprints.org/manuscript/202004.0457/v1

Des-Gamma Carboxyprothrombin (abnormal form of prothrombin.)

https://en.wikipedia.org/wiki/Des-gamma_carboxyprothrombin

TGF-beta

https://en.wikipedia.org/wiki/Transforming_growth_factor_beta

Matrix metallopeptidases

https://en.wikipedia.org/wiki/Matrix_metallopeptidase

Vitamin K found in some cheeses could help fight COVID-19

https://www.theguardian.com/science/2020/jun/05/vitamin-k-could-help-fight-coronavirus-study-suggests

Budesonide

Our video about dexamethasone. (Errata, in this video the Th1 and Th2 roles are reversed by mistake.)

https://youtu.be/7wszDkRQlhk

Inhaled Corticosteroids (Budesonide)

Dr. Richard Bartlett's approach for COVID-19 patients.

https://youtu.be/CX-sXy3rW40

Budesonide excerpt from Wikipedia

 It is available as an inhaler, pill, nasal spray, and rectal forms.[1][2] The inhaled form is used in the long-term management of asthma and chronic obstructive pulmonary disease (COPD).[1][3][4] The nasal spray is used for allergic rhinitis and nasal polyps.[2][5] The pills in a delayed release form and rectal forms may be used for inflammatory bowel disease including Crohn's disease, ulcerative colitis and microscopic colitis

Dr. Richard Bartlett says he has been treating successfully with Budesonide

https://www.youtube.com/watch?v=eDSDdwN2Xcg&feature=youtu.be

Dr. Larry Wilson says no there is no benefit

https://www.mrt.com/news/article/Wilson-No-benefit-using-inhaled-steroids-for-15390142.php

Budesonide

https://en.wikipedia.org/wiki/Budesonide

Corticosteroids

https://en.wikipedia.org/wiki/Corticosteroid

Famotidine (H2 Receptor Antagonist)

Famotidine (H2 Receptor Antagonist) 

https://youtu.be/TtN0gwP16cc

MATH+ '+' protocol advocates the use of Famotidine based on the study showing reduction in the risk of intubation and death in COVID-19 patients.

Famotidine, sold under the brand name Pepcid among others, is a medication that decreases stomach acid production.[2] It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome.[2] It is taken by mouth or by injection into a vein.[2] It begins working within an hour.[2]

Common side effects include headache, intestinal upset, and dizziness.[2] Serious side effects may include pneumonia and seizures.[2][3] Use in pregnancy appears safe but has not been well studied while use during breastfeeding is not recommended.[4] It is a histamine H2 receptor antagonist.[2]

Famotidine

https://en.wikipedia.org/wiki/Famotidine

Gastrin

https://en.wikipedia.org/wiki/Gastrin

Enterochromoaffin-like cells

https://en.wikipedia.org/wiki/Enterochromaffin-like_cell

HCQ updates

Two studies showing the good outcomes of using Hydroxychloroquine and Azithromycin in the early phase of the COVID-19 disease.

https://youtu.be/vgQqT2xbXlo

HCQ + AZ

Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis - ScienceDirect

HCA + AZ + Zinc

https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1

HCQ + AZ

A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.

A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.

CURB score for the risk assessment of death in pneumonia 

https://en.wikipedia.org/wiki/CURB-65

NEWS Score for COVID-19

https://www.mdcalc.com/national-early-warning-score-news

Norepinephrine (NE)

Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone and neurotransmitter.

Norepinephrine

https://en.wikipedia.org/wiki/Norepinephrine

Catecholamines

https://en.wikipedia.org/wiki/Catecholamine

Management of Critically Ill Adults With COVID-19

https://jamanetwork.com/journals/jama/fullarticle/2763879

Organization of the sympathetic system

https://en.wikipedia.org/wiki/Sympathetic_nervous_system

Chromaffin cells of the suprarenal glands that release catecholamines

https://en.wikipedia.org/wiki/Chromaffin_cell

Interleukin 6

https://en.wikipedia.org/wiki/Interleukin_6#:~:text=IL%2D6%20can%20be%20secreted,%2Dlike%20receptors%20(TLRs).

Shock

https://en.wikipedia.org/wiki/Shock_(circulatory)

Cytokines and shock

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378830/

Cytokines causing vasoactivity

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730638/#:~:text=Cytokines%20induce%20macrophage%2Dtype%20NOS%20in%20VSMCs.&text=TNF%2D%CE%B1%20(produced%20by%20macrophages,to%20the%20hyperemia%20of%20inflammation.

Dr. Salman Tahir Saleem

Here we present the case of Dr. Salman Tahir. He was a young man studying in 4th year medicine. He developed viral meningitis with COVID-19 and passed away in a few days.

A Rare Case of Viral Meningitis

Dr. Salman Tahir (RIP)

https://youtu.be/qx570o5o3co

Dr. Salman Tahir’s mother’s interview:

https://www.youtube.com/watch?v=vB7pyZraMsk

References:

Dexibuprofen

https://en.wikipedia.org/wiki/Dexibuprofen

Ceftriaxone

https://en.wikipedia.org/wiki/Ceftriaxone

Vancomycin

https://en.wikipedia.org/wiki/Vancomycin

Acyclovir

https://en.wikipedia.org/wiki/Aciclovir

Dexamethasone

https://en.wikipedia.org/wiki/Dexamethasone

Meropenem

https://en.wikipedia.org/wiki/Meropenem

Tocilizumab

https://en.wikipedia.org/wiki/Tocilizumab

Dr. Salman Tahir - Labs

Continuing to discuss Dr. Salman Tahir’s case (RIP.) Today we will discuss the labs.

p.s. please avoid commenting to offer what could have been done differently. His family’s point of view is to offer this information to help save lives.

Increased neutrophils and NETosis

https://www.the-scientist.com/news-opinion/neutrophil-extracellular-traps-may-augur-severe-covid-19-67588

Patients with low lymphocyte count lymphopenia have poorer outcome

https://jintensivecare.biomedcentral.com/articles/10.1186/s40560-020-00453-4

Calculating the anion gap

AG = Sodium - (chloride and bicarb)

https://en.wikipedia.org/wiki/Anion_gap

High anion gap acidosis

Mnemonic: MUDPILES

Methanol

Uremia

Diabetic ketoacidosis

Paracetamol

Infection, iron, isoniazid leading to lactic acidosis

Ethylene glycol

Salicylates

https://en.wikipedia.org/wiki/High_anion_gap_metabolic_acidosis#:~:text=High%20anion%20gap%20metabolic%20acidosis%20is%20a%20form%20of%20metabolic,enough%20acid%20from%20the%20body.

Arterial blood gases (ABGs)

https://en.wikipedia.org/wiki/Arterial_blood_gas_test

Lymphocytic meningitis

https://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702007000500010

Platelet count can reduce by heparin in some cases

https://www.ahajournals.org/doi/full/10.1161/circulationaha.106.632653

Increased LDH levels

https://en.wikipedia.org/wiki/Lactate_dehydrogenase

Vitamin K is essential co-enzyme for post-translational modification of the clotting factors II, VII, IX, and X.

Study links better vitamin K status with improved COVID-19 outcomes

https://www.nutritioninsight.com/news/study-links-better-vitamin-k-status-with-improved-covid-19-outcomes.html

WHO's list of essential medicines: safest and most effective drug needed in the health system.

Used for acetaminophen/paracetamol overdose and to loosen thick mucus.
Appears to be safe in pregnancy

How does NAC break disulfide bonds?
https://www.researchgate.net/figure/Structural-formula-of-N-acetylcysteine-NAC-A-Disulfide-bonds-in-proteins-P-can-be_fig1_299401240

It increases the levels of glutathione in paracetamol overdose.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241507/

Role of glutathione in immunity and inflammation in the lung
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048347/

Disulfide bond reduction of vWF
https://www.ncbi.nlm.nih.gov/pubmed/20946172

N-Acetylcysteine as an antioxidant and disulfide breaking agent: the reasons why
https://www.tandfonline.com/doi/full/10.1080/10715762.2018.1468564

NAC functions
https://www.sciencedirect.com/topics/chemistry/cysteine

Latest updates about the Ivermectin, Remdesivir, and Leronlimab

Ivermectin shows good results even in the late stage of COVID-19

https://youtu.be/wR6CuBu_mA8

Ivermectin’s in vitro viral inhibition study

https://www.sciencedirect.com/science/article/pii/S0166354220302011

A preprint (yet to be peer reviewed) study

https://www.medrxiv.org/content/10.1101/2020.06.06.20124461v2

A private health group in Dominican Republic finds good results from Ivermectin

https://www.trialsitenews.com/president-of-dominican-republics-largest-private-health-group-discusses-the-success-of-ivermectin-as-a-treatment-for-early-stage-covid-19/

Remdesivir

https://www.nejm.org/doi/full/10.1056/NEJMoa2007764

Gilead’s press release for Remdesivir SIMPLE trial

https://www.gilead.com/news-and-press/press-room/press-releases/2020/6/gilead-announces-results-from-phase-3-trial-of-remdesivir-in-patients-with-moderate-covid-19

Remdesivir May 22nd study (I believe this study allowed WHO to approve their emergency use authorization.)

https://www.nejm.org/doi/full/10.1056/NEJMoa2007764?query=featured_home

Remdesivir pricing

https://www.npr.org/sections/health-shots/2020/06/29/884648842/remdesivir-priced-at-more-than-3-100-for-a-course-of-treatment

Leronlimab

https://www.targetedonc.com/view/cemiplimab-upholds-efficacy-in-3-year-follow-up-for-advanced-cutaneous-squamous-cell-carcinoma

https://www.cytodyn.com/pipeline/covid-19

Phase III trial in Mexico

https://markets.businessinsider.com/news/stocks/cytodyn-and-nih-of-mexico-complete-memorandum-of-understanding-to-conduct-small-covid-19-phase-3-trial-for-severe-and-critically-ill-patients-1029349155#

Selenium disables protein disulfide isomerase (PDI) enzyme of the viruses.

It helps proliferate Natural Killer cells.

It helps proliferate T lymphocytes in the presence of phytoncides from onions.

Vitamin D, E and Selenium work better together

It reduces thrombosis in the vessels.

It is part of Glutathione to work as an antioxidant

Selenium and COVID-19

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246001/

Selenium with Ebola virus

http://www.sciencedomain.org/download/NzI3NkBAcGY.pdf

Functions of PDI

https://www.researchgate.net/figure/Thiol-disulfide-exchange-reactions-between-protein-disulfide-isomerase-PDI-proteins-and_fig6_51853364

MATH+ removes hydroxychloroquine and chloroquine from their protocol with negative commentary. We will look at the studies they used to base their decision on.

Donate here to support my work:

https://paypal.me/mobeensyed?locale.x=en_US

Study 1

https://www.acpjournals.org/doi/10.7326/M20-2496

Study 2

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765499

Study 3

https://www.bmj.com/content/369/bmj.m1844

Study 4

https://jamanetwork.com/journals/jama/fullarticle/2766117

Study 5

https://www.nejm.org/doi/full/10.1056/NEJMoa2016638

Suggestion to use Zinc with HCQ

https://pubmed.ncbi.nlm.nih.gov/32335560/

Glenmark's FabiFlu approved for coronavirus treatment in India, costs Rs 103 per tablet

Mumbai-based Glenmark Pharmaceuticals have launched a new antiviral drug - Favipiravir with brand name FabiFlu - for the treatment of mild to moderate Covid-19 patients. The firm has become the first Indian company to commercially launch the antiviral drug.

https://www.indiatoday.in/india/story/coronavirus-treatment-drug-glenmark-fabiflu-favipiravir-launch-india-rs-103-per-tablet-reduce-viral-load-1691066-2020-06-20

Coronavirus replication

https://www.ncbi.nlm.nih.gov/books/NBK554776/figure/article-52171.image.f1/

RdRp is the main enzyme of transcription-replication complex

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2322833/

Favipiravir mechanism of action and its study

https://www.biorxiv.org/content/10.1101/2020.05.15.098731v1.full.pdf+html

Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study

https://www.sciencedirect.com/science/article/pii/S2095809920300631?via%3Dihub

Potential coronavirus drug approved for marketing

Favipiravir, an antiviral that has shown potential in treating the novel coronavirus, was approved for marketing, the Taizhou government of Zhejiang province announced Sunday.

https://www.chinadaily.com.cn/a/202002/17/WS5e49efc2a310128217277fa3.html

Therapeutic options for the 2019 novel coronavirus (2019-nCoV)

Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials.

https://www.nature.com/articles/d41573-020-00016-0

Fujifilm Announces the Start of a Phase III Clinical Trial of Influenza Antiviral Drug Avigan (favipiravir) on COVID-19 in Japan and Commits to Increasing Production

https://www.drugs.com/clinical_trials/fujifilm-announces-start-phase-iii-clinical-trial-influenza-antiviral-avigan-favipiravir-covid-19-18505.html

Low dose radiation with promising outcome

https://www.medrxiv.org/content/10.1101/2020.06.03.20116988v1

India starts trial for the low dose radiation therapy trial

https://clinicaltrials.gov/ct2/show/NCT04394793

Iran is starting a low dose therapy trial

https://clinicaltrials.gov/ct2/show/NCT04390412

Low dose radiation therapy, a double edged sword?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169900/

Reinfection?

https://propakistani.pk/2020/06/23/pakistan-reports-1st-case-of-coronavirus-reinfection/

Study

Immunity reduces after 2 months

https://www.nature.com/articles/s41591-020-0965-6

Article about this study

https://newatlas.com/health-wellbeing/covid19-immunity-antibody-asymptomatic-coronavirus-resistance-duration/

Interleukin 6

https://en.wikipedia.org/wiki/Interleukin_6

We are continuing with our discussion about the hypercoagulability in the COVID-19 (SARS-COV-2) patients.

We will discuss the extrinsic and intrinsic coagulation cascades. We will discuss the clot formation and then the clot dissolution.

D-Dimers
https://en.wikipedia.org/wiki/D-dimer
A four-fold increase in the protein is a reliable indicator of mortality in those suffering from COVID-19.[2][3]

D-Dimers scoring
https://en.wikipedia.org/wiki/Deep_vein_thrombosis#Diagnosis

Fibrinolysis by plasmin and drugs. Note how the t-plasminogen activator (tPA) and Urokinase activate the plasminogen to plasmin. Which then breaks down the clot. Notice that this is a slow process.
https://en.wikipedia.org/wiki/Fibrinolysis

Disseminated intravascular coagulation
https://en.wikipedia.org/wiki/Disseminated_intravascular_coagulation
blood clots form throughout the body, blocking small vessels.

As the clotting factors and platelets are used up, bleeding may occur. Resulting in the blood in the urine, stool, or skin
Organ failure may ensue.

In this discussion, we will cover the following topics:
1. What are (oxidation-reduction) ReDox operations?
2. Why does gaining an electron means reduction?
3. What are reactive oxygen species, and why are they bad?
4. What is the role of NADPH in redox operations in our bodies?
5. What the HMP shunt?
6. How does G6PD help us produce NADPH?
7. What happens in G6PD deficiency?
8. It is an X-linked recessive disorder.
9. Men get the active disease.
10. Women are carriers or may have a trait.
11. This deficiency helps us against malaria.
12. RBCs cannot handle oxidative stress when G6PD is deficient.
13. What are bite cells? What are Heinz bodies?
14. What is sulfhydryl oxidation?
15. The symptoms of G6PD.
16. Diagnosis of G6PD

Leronlimab disrupts CCL5/CCR5 axis to reduce cytokine storm. It has been used in HIV, Cancer, and other conditions. There are studies that show it may be effective and safe in COVID-19 patients as well.

A good comprehensive article

https://www.genengnews.com/covid-19-candidates/cytodyn/

A study on COVID-19 patients

https://www.researchsquare.com/article/rs-26517/v1

Clinical trials for Leronlimab

https://clinicaltrials.gov/ct2/show/NCT04347239

https://clinicaltrials.gov/ct2/show/NCT04343651

A Promising Drug for the Treatment of Severe Lung Inflammation in COVID-19 Patients: Montefiore-Einstein Scientists Lead Two Trials of Leronlimab

CytoDyn site

https://www.cytodyn.com/newsroom/press-releases/detail/426/manuscript-describes-how-cytodyns-leronlimab-disrupts

CCR5

https://en.wikipedia.org/wiki/CCR5

What are humanized antibodies?

https://en.wikipedia.org/wiki/Humanized_antibody

CCL3

https://www.frontiersin.org/articles/10.3389/fimmu.2020.00306/full

CCL4

https://en.wikipedia.org/wiki/CCL4

CCL5

https://en.wikipedia.org/wiki/CCL5

MATH++ Protocol for COVID-19 (Part 2)

What are histiocytes? (Macrophages and Dendritic cells in the tissues and monocytes in the blood.)
https://en.wikipedia.org/wiki/Histiocyte#:~:text=A%20histiocyte%20is%20a%20vertebrate,of%20the%20organism's%20immune%20system.

What is macrophage activation syndrome?
Overactivity of the macrophages that upregulates the immune system. Sort of a cytokine storm.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124446/

What is Sepsis? Increased breathing rate, impaired consciousness, low blood flow
https://en.wikipedia.org/wiki/Sepsis


What is ferritin? A protein that binds with the ferric inside the cells to store it.
https://en.wikipedia.org/wiki/Ferritin

How do steroids suppress inflammation?
https://www.frontiersin.org/articles/10.3389/fendo.2018.00235/full

Type I interferons
https://en.wikipedia.org/wiki/Interferon_type_I

Type II interferons
https://en.wikipedia.org/wiki/Interferon_type_II

Interleukin 6 Actions.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176007/

Lactate dehydrogenase
https://en.wikipedia.org/wiki/Lactate_dehydrogenase


MATH+ is a fascinating protocol. We have added another plus to it to add some of our modifications.
Here is the link to the protocol: https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf

Protocol refers to the L-Type and H-Type phenotypes of COVID-19 patients. Here is a link to these types and the mechanics:
https://pulmccm.org/ards-review/covid-19-associated-ards-cards-the-l-phenotype/


Here is a link showing that if we ventilate an L-Type phenotype patient, then we add to their dead space.
https://pulmccm.org/ards-review/icu-physiology-1000-words-high-flow-oxygen-therapy/

What does the recruiting ability of the lungs mean? Merely opening up the closed alveoli
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00675-7

Melatonin is a safe over the counter medication. It has anti-inflammatory, antioxidant, and anti-viral (other than COVID-19) effects. MATH+ protocol suggests melatonin to be given at almost all the stages of the disease. Here we discuss the synthesis and the mechanism of action of melatonin.

COVID-19: Melatonin as a potential adjuvant treatment

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102583/

Difference between oxidative, aerobic and anaerobic glycolysis.

https://www.crossfit.com/essentials/understanding-the-warburg-effect-the-metabolic-requirements-of-cell-proliferation

Warburg effect

https://en.wikipedia.org/wiki/Warburg_effect_(oncology)

Melatonin

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211589/

Magnesium takes part in more than 300 reactions in our body. It is the second most abundant intracellular cation.

It is anti-inflammatory, excitable membrane stabilizer, and helpful in biomolecule synthesis.

Magnesium in COVID-19

https://www.medrxiv.org/content/10.1101/2020.06.01.20112334v1

Effects of oral magnesium supplementation on inflammatory markers in middle-aged overweight women

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685774/

Magnesium and electrolyte imbalances

http://www.mgwater.com/schroll.shtml

Magnesium functions

https://www.ncbi.nlm.nih.gov/books/NBK519036/

Magnesium

https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/#:~:text=Magnesium%20is%20a%20cofactor%20in,%2C%20oxidative%20phosphorylation%2C%20and%20glycolysis.

Magnesium deficiency and endotoxin damage

https://pubmed.ncbi.nlm.nih.gov/8001362/

Magnesium

https://en.wikipedia.org/wiki/Magnesium

In this video, we will discuss the ICU patient management as suggested by Dr. Paul Marik in his MATH+ Protocol.

MATH+ treatment protocol

https://covid19criticalcare.com/treatment-protocol/

Enoxaparain

https://en.wikipedia.org/wiki/Enoxaparin_sodium

tPA (tissue plasminogen activator)

https://en.wikipedia.org/wiki/Tissue_plasminogen_activator

Antithrombin

https://en.wikipedia.org/wiki/Antithrombin

Factor XIII (Fibrin stabilizing factor)

https://en.wikipedia.org/wiki/Factor_XIII

Interleukin 1

https://en.wikipedia.org/wiki/Interleukin-1_family

Interleukin 1 inhibitor (Anakinra)

https://en.wikipedia.org/wiki/Anakinra

High dose of vitamin C can mask hypoglycemia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773272/#:~:text=In%20conclusion%2C%20high%20concentrations%20of,high%20dose%20of%20vitamin%20C.

What are histiocytes? (Macrophages and Dendritic cells in the tissues and monocytes in the blood.)

https://en.wikipedia.org/wiki/Histiocyte#:~:text=A%20histiocyte%20is%20a%20vertebrate,of%20the%20organism's%20immune%20system.

What is macrophage activation syndrome? 

Overactivity of the macrophages that upregulates the immune system. Sort of a cytokine storm.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124446/

What is Sepsis? Increased breathing rate, impaired consciousness, low blood flow

https://en.wikipedia.org/wiki/Sepsis

What is ferritin? A protein that binds with ferric inside the cells to store it.

https://en.wikipedia.org/wiki/Ferritin

How do steroids suppress inflammation?

https://www.frontiersin.org/articles/10.3389/fendo.2018.00235/full

Type I interferons

https://en.wikipedia.org/wiki/Interferon_type_I

Type II interferons

https://en.wikipedia.org/wiki/Interferon_type_II

Interleukin 6 Actions.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176007/

Lactate dehydrogenase

https://en.wikipedia.org/wiki/Lactate_dehydrogenase

MATH+ is a fascinating protocol. We have added another plus to it to add some of our modifications.

Here is the link to the protocol: https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf

Protocol refers the L-Type and H-Type phenotypes of the COVID-19 patients. Here is a link to these types and the mechanics:

https://pulmccm.org/ards-review/covid-19-associated-ards-cards-the-l-phenotype/

Here is a link showing that if we ventilate an L-Type phenotype patients then we add to their dead space.

https://pulmccm.org/ards-review/icu-physiology-1000-words-high-flow-oxygen-therapy/

What does the recruitability of the lungs mean? Simply opening up the closed alveoli

https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00675-7

Iodine and its medical uses

Iodine and Its Medical Uses 

https://youtu.be/F4pn-YEdfOU

Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens.

Donate to support my work:

https://paypal.me/mobeensyed?locale.x=en_US

Thyroid hormones

https://en.wikipedia.org/wiki/Thyroid_hormones

Iodothyroinine deiodinase

https://en.wikipedia.org/wiki/Iodothyronine_deiodinase

Antiseptics and Disinfectants: Activity, Action, and Resistance

Antiseptics usually mean the biocides applied to skin

Disinfectants usually mean the biocides applied to surfaces

These terms are interchangably used as well

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88911/

Iodine

https://en.wikipedia.org/wiki/Iodine

Povidone Iodine

https://en.wikipedia.org/wiki/Povidone-iodine

Potassium Iodide

https://en.wikipedia.org/wiki/Potassium_iodide

Jod-Basedow Phenomenon

https://en.wikipedia.org/wiki/Jod-Basedow_phenomenon

Grave’s disease

https://en.wikipedia.org/wiki/Graves%27_disease

Hashimoto’s Thyroiditis 

https://en.wikipedia.org/wiki/Hashimoto%27s_thyroiditis

Anterior Pituitary

https://en.wikipedia.org/wiki/Anterior_pituitary

Epoprostenol is an exogenous PGI2.

PGI2 - Prostaglandin I2 or prostacyclin

It is a platelet aggregation inhibitor and a vasodilator.

Prostacyclin inhibits ADP dependent platelet aggregation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224326/

Epoprostenol

https://en.wikipedia.org/wiki/Prostacyclin

Platelets and their activation

https://en.wikipedia.org/wiki/Platelet

Aspirin has antithrombotic, anti-inflammatory, analgesic, and anti-pyretic effects.

Aspirin plus Vitamin D trial for COVID-19

The LEAD COVID-19 Trial: Low-risk, Early Aspirin and Vitamin D to Reduce COVID-19 Hospitalizations (LEAD COVID-19)

https://clinicaltrials.gov/ct2/show/NCT04363840

Aspirin

http://tmedweb.tulane.edu/pharmwiki/doku.php/aspirin

Leukotrienes and allergies

https://en.wikipedia.org/wiki/Leukotriene#:~:text=Leukotrienes%20are%20a%20family%20of,the%20enzyme%20arachidonate%205%2Dlipoxygenase.

Dexamethasone

Errata: Th1 and Th2 are reversed in the diagram and narration.

Oxford RECOVERY Trial statement

https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf

Statnews article for dexamethasone results

https://www.statnews.com/2020/06/16/major-study-finds-common-steroid-reduces-deaths-among-patients-with-severe-covid-19/

WHO Statement for Dexamethasone

https://www.who.int/news-room/detail/16-06-2020-who-welcomes-preliminary-results-about-dexamethasone-use-in-treating-critically-ill-covid-19-patients

Warning: abrupt withdrawal can cause acute adrenal insufficiency

Thiamine (HAT Study)

Excerpt from WikiPedia (https://en.wikipedia.org/wiki/Thiamine)

Thiamine, also known as thiamin or vitamin B1, is a vitamin found in food, and manufactured as a dietary supplement and medication.[2][3] Food sources of thiamine include whole grains, legumes, and some meats and fish.[2] Grain processing removes much of the thiamine content, so in many countries cereals and flours are enriched with thiamine.[4][2] Supplements and medications are available to treat and prevent thiamine deficiency and disorders that result from it, including beriberi and Wernicke encephalopathy.[1] Other uses include the treatment of maple syrup urine disease and Leigh syndrome.[1] They are typically taken by mouth, but may also be given by intravenous or intramuscular injection.[1][5]

SOFA score

https://en.wikipedia.org/wiki/SOFA_score

Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock

https://journal.chestnet.org/article/S0012-3692(16)62564-3/fulltext

Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) for the Treatment of Sepsis. Focus on Ascorbic Acid

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265973/

Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis: The ORANGES Trial

https://pubmed.ncbi.nlm.nih.gov/32194058/

Thiamine deficiency

https://emedicine.medscape.com/article/116930-overview#:~:text=The%20chronic%20form%20of%20wet,aldosterone%20system%20in%20the%20kidneys.

Various corticosteroids and their difference

https://www.aafp.org/afp/1998/0801/p443.html#:~:text=Systemic%20corticosteroids%20have%20been%20used,times%20more%20potent%20than%20hydrocortisone.

What are histiocytes? (Macrophages and Dendritic cells in the tissues and monocytes in the blood.)

https://en.wikipedia.org/wiki/Histiocyte#:~:text=A%20histiocyte%20is%20a%20vertebrate,of%20the%20organism's%20immune%20system.

What is macrophage activation syndrome? 

Overactivity of the macrophages that upregulates the immune system. Sort of a cytokine storm.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124446/

What is Sepsis? Increased breathing rate, impaired consciousness, low blood flow

https://en.wikipedia.org/wiki/Sepsis

What is ferritin? A protein that binds with ferric inside the cells to store it.

https://en.wikipedia.org/wiki/Ferritin

How do steroids suppress inflammation?

https://www.frontiersin.org/articles/10.3389/fendo.2018.00235/full

Type I interferons

https://en.wikipedia.org/wiki/Interferon_type_I

Type II interferons

https://en.wikipedia.org/wiki/Interferon_type_II

Interleukin 6 Actions.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176007/

Lactate dehydrogenase

https://en.wikipedia.org/wiki/Lactate_dehydrogenase

MATH+ is a fascinating protocol. We have added another plus to it to add some of our modifications.

Here is the link to the protocol: https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf

Protocol refers the L-Type and H-Type phenotypes of the COVID-19 patients. Here is a link to these types and the mechanics:

https://pulmccm.org/ards-review/covid-19-associated-ards-cards-the-l-phenotype/

Here is a link showing that if we ventilate an L-Type phenotype patients then we add to their dead space.

https://pulmccm.org/ards-review/icu-physiology-1000-words-high-flow-oxygen-therapy/

What does the recruitability of the lungs mean? Simply opening up the closed alveoli

https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00675-7

Update on vaccines

https://www.moneycontrol.com/news/trends/health-trends/coronavirus-crisis-these-four-covid-19-vaccines-are-ahead-of-the-pack-5247601.html

https://www.sciencemag.org/news/2020/04/covid-19-vaccine-protects-monkeys-new-coronavirus-chinese-biotech-reports

https://www.healthline.com/health/clinical-trial-phases#phase-iv

University of Oxford coronavirus vaccine: everything we know so far

A phase two trial and a June goal: This week's updates on the race for a coronavirus vaccine

A phase two trial and a June goal: This week's updates on the race for a coronavirus vaccine

What it's like inside the Oxford trial leading the race for coronavirus vaccine

Clinical Trial Phases: What Happens in Phase 0, I, II, III, and IV

Thiamine (HAT Study)

Excerpt from WikiPedia (https://en.wikipedia.org/wiki/Thiamine)

Thiamine, also known as thiamin or vitamin B1, is a vitamin found in food, and manufactured as a dietary supplement and medication.[2][3] Food sources of thiamine include whole grains, legumes, and some meats and fish.[2] Grain processing removes much of the thiamine content, so in many countries cereals and flours are enriched with thiamine.[4][2] Supplements and medications are available to treat and prevent thiamine deficiency and disorders that result from it, including beriberi and Wernicke encephalopathy.[1] Other uses include the treatment of maple syrup urine disease and Leigh syndrome.[1] They are typically taken by mouth, but may also be given by intravenous or intramuscular injection.[1][5]

SOFA score

https://en.wikipedia.org/wiki/SOFA_score

Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock

https://journal.chestnet.org/article/S0012-3692(16)62564-3/fulltext

Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) for the Treatment of Sepsis. Focus on Ascorbic Acid

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265973/

Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis: The ORANGES Trial

https://pubmed.ncbi.nlm.nih.gov/32194058/

Thiamine deficiency

https://emedicine.medscape.com/article/116930-overview#:~:text=The%20chronic%20form%20of%20wet,aldosterone%20system%20in%20the%20kidneys.

Various corticosteroids and their difference

https://www.aafp.org/afp/1998/0801/p443.html#:~:text=Systemic%20corticosteroids%20have%20been%20used,times%20more%20potent%20than%20hydrocortisone.

Tocilizumab
https://en.wikipedia.org/wiki/Tocilizumab

interleukin 6 
IL-6 in Inflammation, Immunity, and Disease

https://en.wikipedia.org/wiki/Interleukin_6

How to decode loci on chromosomes
https://en.wikipedia.org/wiki/Locus_(genetics)

Neutrophils
https://en.wikipedia.org/wiki/Neutrophil

Th17 Cells
https://en.wikipedia.org/wiki/T_helper_17_cell

IL6 Receptor blocker study
https://www.sanofi.com/en/media-room/press-releases/2020/2020-04-27-12-58-00

IL6 Receptor blocker study from France (in the French language)
https://www.aphp.fr/contenu/le-tocilizumab-ameliore-significativement-le-pronostic-des-patients-avec-pneumonie-covid

Notes and references for Herd Immunity and a Second Wave

https://www.jhsph.edu/covid-19/articles/achieving-herd-immunity-with-covid19.html

https://www.google.com/amp/s/www.sciencealert.com/why-herd-immunity-will-not-save-us-from-the-covid-19-pandemic/amp

https://www.google.com/amp/s/www.mercurynews.com/2020/04/12/coronavirus-can-we-avoid-a-second-wave-of-infections/amp/

https://www.npr.org/sections/coronavirus-live-updates/2020/04/13/832981899/emergency-declared-in-japanese-prefecture-hit-by-2nd-wave-of-coronavirus-infecti

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30845-X/fulltext https://www.google.com/amp/s/www.aljazeera.com/amp/news/2020/04/200413110301074.html

https://www.businessinsider.com/coronavirus-germany-covid-19-immunity-certificates-testing-social-distancing-lockdown-2020-3

COVID-19 Insights. An Invitro VIRAL BLOCKER Camostat Mesylate

Links to the news

Acute MI incidence reduced during the lockdown. It will increase once the lockdown lifted.
https://www.nejm.org/doi/full/10.1056/NEJMc2015630
Infection can spread by aerosol
https://www.nejm.org/doi/full/10.1056/NEJMc2009324
CDC thinks that the virus spreads more from humans to humans than the fomites.
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html


Links to the studies and medical concepts

The Impact of Camostat Mesylate on COVID-19 Infection (CamoCO-19)
From https://clinicaltrials.gov/ct2/show/NCT04321096
Study that proves Camostat Mesylate blocks viral (SARS-COV-2) entry into the cells
https://www.eurekalert.org/pub_releases/2020-03/dpp-pso030520.php

How serine proteases cut the proteins
https://en.wikipedia.org/wiki/Serine_protease

Camostat mesylate
https://en.wikipedia.org/wiki/Camostat
Camostat invitro study
https://pubmed.ncbi.nlm.nih.gov/32142651/
Camostat dosage
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188520/
Camostat trials
https://clinicaltrials.gov/ct2/show/NCT04321096
https://clinicaltrials.gov/ct2/show/NCT04353284

Spike protein priming
https://link.springer.com/chapter/10.1007/978-3-319-75474-1_4

Six helices for the S2 subunit of the Spike protein
https://www.researchgate.net/figure/The-fusion-core-structureThe-fusion-core-is-a-six-helix-bundle-with-three-HR2-helices_fig3_23986117

How does COVID-19 severity changes in people with various blood groups?

Are African Americans at a higher risk of severe COVID-19?

Blood group A is at a significantly higher risk of COVID-19 infection and severity.
Blood group O is at a significantly lower risk of COVID-19 infection and severity.
https://www.medrxiv.org/content/10.1101/2020.03.11.20031096v2

https://www.medrxiv.org/content/10.1101/2020.03.11.20031096v2.full.pdf+html

Blood type O have a lower level of vWF
https://www.ncbi.nlm.nih.gov/books/NBK2267/
https://journals.lww.com/hemasphere/Fulltext/2017/12000/Knowledge_of_Blood_Group_Decreases_von_Willebrand.3.aspx


https://www.pharmacytimes.com/news/study-vaccine-skepticism-may-be-caused-by-cognitive-or-affective-differences

Blood groups
A blood group has A antigen
https://www.ncbi.nlm.nih.gov/books/NBK2267/


Black Americans are dying at a 2.6 times higher rate than white Americans. (NY)
https://www.apmresearchlab.org/covid/deaths-by-race

Chicago Black Americans make 70% of all deaths from coronavirus, while their population is only 29% of the city.
https://www.wbez.org/stories/in-chicago-70-of-covid-19-deaths-are-black/dd3f295f-445e-4e38-b37f-a1503782b507


Black Americans have higher von Willebrand Factor
https://www.ncbi.nlm.nih.gov/pubmed/11343385

Vitamin D levels are low in Black Americans
https://www.ncbi.nlm.nih.gov/pubmed/16549493

Adiponectin and hypertension
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729220/

Reduces adiponectin receptor function in obesity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486142/

Reduced adiponectin release in obese people leads to hypertension, atherosclerosis, CKD, metabolic syndromes, COPD, sleep apnea, etc.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109424/

May 6th Update

Military bans coronavirus survivors from joining

https://www.militarytimes.com/news/your-military/2020/05/06/coronavirus-survivors-banned-from-joining-the-military/?utm_source=facebook.com&utm_campaign=Socialflow%20NAV&utm_medium=social&fbclid=IwAR2Icc3GriUqVg9Q772GezvG2JAMSHW9gBnpOeoNpDBp19qtd6EQXvq2HrM

Do we have distinct SARS-COV-2 types?

https://www.sciencedirect.com/science/article/pii/S1567134820301829?fbclid=IwAR0s97ISOBcp9qISJcl97LTvx_Wa35FSiZwoIXahcWFVFTR-LShU6WV6U50

Check the emerging and mutating/adapting strains of the SARS-COV-2 here:

https://nextstrain.org/ncov/global

https://academic.oup.com/ve/advance-article/doi/10.1093/ve/veaa034/5827470?searchresult=1&fbclid=IwAR1HCi2LOGwpTnC0n5Sp8PUeHYSjG4h0oz94F2Z24xLJ-O6tduxgUm5Ep_A

Do we have two strains, S and L?

https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa036/5775463

A counter to the S and L strain message:

https://watermark.silverchair.com/veaa034.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAoAwggJ8BgkqhkiG9w0BBwagggJtMIICaQIBADCCAmIGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM9MvlEXkPAB8_ZbL8AgEQgIICM8II09GHKgunI-oKpZDFzasmddU0nYXB_L8HNxZNHCbwYYT6TH2yzg0FzNEB-o0TvGo0my7ThutD9eq_XmQhiBc3vOqzJ8HERJ3-l23PB31OSCqbJOcD71Ncvj2Trz-uFPAfLjTZmJdF0QUagrJzh8LmntFOyX-xPqZz861E3b28WRuC2QJ8s8tQ4CVBkyxuFEYdwWCHdTP7iD4IZT8asG3iB9Q0HvPu1p-3kb_8tIL-wxHhJ2CFNNztmqLkhdFc2SZhgfMhPLROrobxiXGkcX70Ha1dNB7hTGoG-hDp6lLFJSvGm1W0z4vcaX7dO472Wn9Q68XKBwPqOVcKcKkjF__eZWORkWxj-TU6jMeSBsw1pRtQWwM3ke-L_SsL5VZaLXC7uyHtqtpWxmmbWOixg5I0h1oetHPI8wKDUYa3YnK67mlfKcmFAMFQdiWmU1gK8Ye3ZZee_6-wy6AlvtYlO6QGZ7RFwTUUwevQ1aJk5pUsnGmdmwndROiOVgYLjBz4O4U3R2L81jAnE14N1wG5u5F_o1r6MZFoDaq9l9svUHP5dPYUNUbnGj4p-Nv8UAbRFzVBWwM80CbP5OzBVPOBq4_2K9eiiledKaVyzG8k02P0pjgMxiAW4BC99pTS7eoOdFRvv0Ixttwq-8vuTVhE0_rz3QTCXqViorgURXVmGJ9hNEngfYcePMuh51FPBD8Bml_NaryhyAcBxq3jjmlyjqbmfv75lOQyysPH260zsDfnt5Qe

Schools are closing after opening.

Israel closes schools after opening
https://www.npr.org/sections/coronavirus-live-updates/2020/06/03/868507524/israel-orders-schools-to-close-when-covid-19-cases-are-discovered

Britain keeps schools closed indefinitely
https://www.theguardian.com/world/2020/mar/18/coronavirus-uk-schools-to-be-closed-indefinitely-and-exams-cancelled
https://www.theguardian.com/education/2020/apr/08/uk-schools-not-reopen-straight-after-easter-officials-insist

India thinks about reopening schools in July
https://www.hindustantimes.com/india-news/as-govt-relaxes-lockdown-decision-to-reopen-schools-in-july/story-fpMKxorsOl2PvDxf0XjffM.html


Is virus becoming weak?

Expert reaction to comments reported in the media by Prof Alberto Zangrillo about the COVID-19 virus in Italy
https://www.sciencemediacentre.org/expert-reaction-to-comments-reported-in-the-media-by-prof-alberto-zangrillo-about-the-covid-19-virus-in-italy/

No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2
https://www.biorxiv.org/content/10.1101/2020.05.21.108506v1

How will it become weak? How do viruses become weak?
https://evolution.berkeley.edu/evolibrary/news/071201_adenovirus
https://www.historyofvaccines.org/index.php/content/articles/viruses-and-evolution

Coronavirus proofreading and the proofreader a target for medication
https://www.biorxiv.org/content/10.1101/2020.04.23.057786v1

RdRp is slowly mutating as well that can result in drug resistance
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02344-6

RdRp resistance is not easy in SARS-COV-2 (Drug discussed is Remdesivir)
https://science.sciencemag.org/content/early/2020/04/30/science.abc1560

A fascinating read why Remdesivir works and Ribavirin does not work on coronaviruses
https://www.asbmb.org/asbmb-today/science/041020/slipping-past-the-proofreader


HCQ study. Expression of concern by the Lancet.
https://www.thelancet.com/journals/lanpub/article/PIIS0140-6736(20)31290-3/fulltext
https://www.reuters.com/article/us-health-coronavirus-who-idUSKBN23A2LT

CoQ10 is an enzyme that takes part in electron transport chain to make energy in our cells.

It is also a good anti-oxidant.

NIH on CoQ10

https://www.nccih.nih.gov/health/coenzyme-q10

Kaiser Permanente on CoQ10 (doses inlaced for various needs.)

https://wa.kaiserpermanente.org/kbase/topic.jhtml?docId=hn-2831009    

Mount Sinai on CoQ10

https://www.mountsinai.org/health-library/supplement/coenzyme-q10

A good article. Avoided discussing the side-effects

https://www.healthline.com/nutrition/coenzyme-q10#section13

CoQ10 Synthesis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943198/

Therapeutic uses of CoQ10

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112525/

CoQ10 reduces the need for steroids in COPD and Asthma patients

https://pubmed.ncbi.nlm.nih.gov/16873952/

No relation of CoQ10 levels and the intensity of COPD and Asthma (a counter point study.)

https://pubmed.ncbi.nlm.nih.gov/16872244/

We discuss the possible usage of the following drugs in mild to moderate cases of COVID-19.

+ Hydroxychloroquine

+ Azithromycin

+ Zinc

+ Quercitin 

+ Vitamin C 

+ Vitamin D

Here are the references and notes:

Hydroxychloroquine and zinc

https://youtu.be/nxwf4rH3d-o

Safe in therapeutic doses especially for short term use. Long term use can cause retinal damage, heart arrhythmias, and blood disorders. See our detailed video about it.

Safe for pregnant and lactating women (infant must be 5kg or more body weight.)

Prophylaxis in India

https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinasprophylaxisforSARSCoV2infection.pdf

Healthcare workers involved in caring for the COVID-19 patients. First day: 400 mg BD. Then 400 mg once weekly for the next 7 weeks. With meals.

Asymptomatic family members of the COVID-19 patients. First day 400 mg BD. Then 400 mg once weekly for the next 3 weeks. With meals.

Not for children under 15 years of age.

Not for the patients with retinopathies and known allergies to hydroxychloroquine or 4-aminoquinoline compounds.

https://reference.medscape.com/drug/plaquenil-hydroxychloroquine-sulfate-343205

https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/

French study using HCQ + Z-Pack

https://www.sciencedirect.com/science/article/pii/S0924857920300996

https://academic.oup.com/ofid/article/7/4/ofaa105/5811022

Half life is about 40 days. Hence, a short therapy can provide a prolonged course of outcome.

First day 400 mg BD. 

Then 200 mg BD.

Mount Sinai

https://www.drbeen.com/corona-information-center/

CDC on Hydroxychloroquine

https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html

FDA’s emergency use authorization (EUA)

https://www.fda.gov/media/136534/download

Azithromycin in pregnancy. FDA category B.

https://www.drugs.com/pregnancy/azithromycin.html

Zinc

https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

Daily allowance 11 mg/day

Quercetin (bioflavonoid supplement.)

https://pubs.acs.org/doi/10.1021/jf5014633#

Apples are high in quercetin (eat apples)

Excerpt

We have previously shown that these polyphenols chelate zinc cations and hypothesized that these flavonoids might be also acting as zinc ionophores, transporting zinc cations through the plasma membrane. 

Sources and dosage

https://www.healthline.com/nutrition/quercetin#sources-and-dosage

Vitamin C

https://www.healthline.com/nutrition/how-much-vitamin-c-should-i-take-daily

Up to 2,000 mg/day supplement as the upper intake level.

Vitamin D

https://www.healthline.com/nutrition/vitamin-d-dosage#section2

33 ng/ml

Consuming 1,000 IU (25 mcg) daily can help bring it to 33 ng/ml

1,000-4,000 IU (25-100 mcg) per day.

Active vitamin D

https://reference.medscape.com/drug/drisdol-calciferol-vitamind-344417

400-800 IU

How long to stay in sun?

https://health.usnews.com/wellness/articles/2018-07-18/how-much-time-in-the-sun-do-you-need-for-vitamin-d

10-15 minutes between 10:00 am to 3:00 pm

Exercise safety to not get sunburnt (sunblocks)

https://www.youtube.com/watch?v=m3J_1B7kJbk

https://www.youtube.com/watch?v=1TJdjhd_XG8

Dr. Vladimir Zelenko

Hydroxychloroquine (somewhat successful. Not impressive.)

Zinc interrupts viral replication.

HCQ - 200 mg BD for 5 days.

In the ICU 400 mg BD the first day, then 200 mg BD.

Zithromax: 500 mg once a day for 5 days.

Zinc sulfate 220 mg daily OD for 5 days.

Parameters:

Milder cases

Young (less than sixty) and healthy. You will be fine.

Shortness of breath will be treated with HCQ + Z-Pack + Zinc

Older population that are sick start them soon.

Success is not to die.

Treatment is $20

Heart rhythm problems. Retinal damage.

Mobeen’s addition to the prescription

Vitamin C

Vitamin D (sunlight)

Recommendation by the Infectious Diseases Society of America

https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/

In this talk we will discuss the specificity and sensitivity of various tests. We will discuss the positive predictive value and negative predictive value as well.

Biosafety lab levels

https://consteril.com/biosafety-levels-difference/

List of approved serology tests for COVID-19

https://www.fda.gov/medical-devices/emergency-situations-medical-devices/eua-authorized-serology-test-performance

Sensitivity and Specificity

https://en.wikipedia.org/wiki/Sensitivity_and_specificity

We will discuss the CDC’s message tomorrow

CDC about the COVID-19 testing and the issues with the testing. 

Interim Guidelines for COVID-19 Antibody Testing | CDC

Medical calculator

https://www.medcalc.org/calc/diagnostic_test.php

Oxford Vaccine Reloaded, Moderna, CDC

Oxford Vaccine US invests $1.2bln
https://www.sciencemag.org/news/2020/05/doubts-greet-12-billion-bet-united-states-coronavirus-vaccine-october

Moderna (5/19) Vaccine
https://www.statnews.com/2020/05/19/vaccine-experts-say-moderna-didnt-produce-data-critical-to-assessing-covid-19-vaccine/

Moderna (5/18) Vaccine
https://www.statnews.com/2020/05/18/early-data-show-moderna-covid-19-vaccine-generates-immune-response/

CanSino Vaccine
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31208-3/fulltext

CanSino trial
https://clinicaltrials.gov/ct2/show/NCT04313127

CDC continues to “reorganize” its information page.
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html

Surface stability of the SARS-COV-2
https://www.medrxiv.org/content/10.1101/2020.03.09.20033217v1.full.pdf

An analysis of other studies (very important to read.)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204655/

Test sensitivity and specificity

FDA’s list
https://www.fda.gov/medical-devices/emergency-situations-medical-devices/eua-authorized-serology-test-performance

Another list
https://www.centerforhealthsecurity.org/resources/COVID-19/serology/Serology-based-tests-for-COVID-19.html

Another good article for tests
The Latest on Coronavirus Testing: New Methods, Accuracy, and Availability- GoodRx

Good article by ASM
https://asm.org/Articles/2020/April/False-Negatives-and-Reinfections-the-Challenges-of

A study on the rtPCR tests

Analytical sensitivity and efficiency comparisons of SARS-COV-2 qRT-PCR primer-probe sets | medRxiv

Early results from the Moderna's coronavirus vaccine trial shows participants developed antibodies against the virus.

From https://www.cnn.com/2020/05/18/health/coronavirus-vaccine-moderna-early-results/index.html

Moderna site
https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19

Meet the company that has just begun testing a coronavirus vaccine in the United States
From https://www.sciencemag.org/news/2017/02/mysterious-2-billion-biotech-revealing-secrets-behind-its-new-drugs-and-vaccines#

Sinovac Announces First Animal Study Results of Vaccine Against COVID-19 Published in SCIENCE

From https://www.businesswire.com/news/home/20200506005601/en/Sinovac-Announces-Animal-Study-Results-Vaccine-COVID-19

COVID-19 vaccine protects monkeys from new coronavirus, Chinese biotech reports
From https://www.sciencemag.org/news/2020/04/covid-19-vaccine-protects-monkeys-new-coronavirus-chinese-biotech-reports

Doubts over Oxford vaccine as it fails to stop coronavirus in animal trials

From https://www.telegraph.co.uk/global-health/science-and-disease/doubts-oxford-vaccine-fails-stop-coronavirus-animal-trials/

Oxford vaccine fails in animals
https://www.google.com/amp/s/www.telegraph.co.uk/global-health/science-and-disease/doubts-oxford-vaccine-fails-stop-coronavirus-animal-trials/amp/

Sinovac vaccine works in animals
https://www.businesswire.com/news/home/20200506005601/en/Sinovac-Announces-Animal-Study-Results-Vaccine-COVID-19

Sinovac vaccine trials continue. No data yet
https://www.webmd.com/lung/news/20200515/pfizer-says-covid-19-vaccine-could-arrive-in-october

Latest State of Affairs May 15, 2020

How are countries doing? And, what did they do?

Georgia Reopens
Not bad

US NY
COVID-19 tracker
https://covid19tracker.health.ny.gov/views/NYS-COVID19-Tracker/NYSDOHCOVID-19Tracker-Map?%3Aembed=yes&%3Atoolbar=no

Population 19.45M
NYC population: 8.39M

1.3M tested
345K positive (~26%)
22,304 fatalities (6.46% of the positive)

Patients: Male 51% Females 48%
Fatalities: Male 58.3% Female 41.7%

109 Children (Age less than 20 y) and 3 Deaths 

New Yorkers are now required to wear a mask and maintain 6 feet distance in public. 

Issued covid-19 inflammatory illness in children
https://coronavirus.health.ny.gov/childhood-inflammatory-disease-related-covid-19

All nursing home staff be tested for COVID-19 twice per week.

NY metrics to guide reopening
https://forward.ny.gov/metrics-guide-reopening-new-york
Monitoring New Infections
• Decline in total hospitalizations
• Decline in deaths
• Decline in new hospitalizations
Health Care Capacity
• Hospital bed capacity (at least 30% of the total beds available.)
• ICU capacity (at least 30% of the total beds available.)
Diagnostic Testing and Contact Tracing Capacity
• Diagnostic testing capacity
o 30 tests per thousand people per month
• Contact tracing capacity

Taiwan
https://www.nbcnews.com/news/world/taiwanese-authorities-stay-vigilant-virus-crisis-eases-n1188781
Population: 23.78M

Cases: 440

Deaths: 7

Temperature checks for visitors

Mobile phones to track for 14 days for mandatory isolation. 

You run out of batteries or the reception is poor, police will show up.

Violation of quarantine: $3,333 to $333,333

Can’t use public transport for international arrivals. 

Special taxis are offered. These taxis are disinfected every day and no other passenger sits in these cabs. 

$116/day driver pay even if it is not used.

A month later, the driver, and the taxi goes in quarantine with GPS signals.

Businesses and facilities check the temperature of the employees and visitors. Names and phones are recorded.

Parents check student’s temperature daily and then at the school gate.

Restaurants are disinfecting daily.
Businesses have disinfectants in the lobbies.

Social distancing continues with gatherings of 100 indoors and 150 outdoors.

Mauritius
https://voxeu.org/article/mauritian-response-covid-19

First African Country with no cases since 4/27

Population: 1.26M

Cases: 332

Deaths: 10

First announcement on 18th March of three cases.

Lockdown

Contact tracing

Phone app for update if you were in 100 meters of an infected patient.

Madagascar
Population: 26.26M

Cases: 238

Deaths: 0

First 3 cases on 3/20

International flights were suspended on 3/20

Lockdown in two cities 

Tourism is affected

Madagascar has a herbal concoction/tea (COVID ORGANICS) that their president believes cures the COVID-19. WHO is working with them.
https://www.aa.com.tr/en/africa/who-to-study-madagascars-drug-to-treat-covid-19-/1840971

Senegal
Population: 15.85M

Cases: 2,310

Deaths: 25

They have a test for under $1 that may detect virus RNA within 10 minutes.
https://www.newscientist.com/article/mg24632823-700-cheap-and-easy-1-coronavirus-test-to-undergo-trials-in-senegal/

Pakistan
Population: 220M

Confirmed: 37K

Deaths: 803

Gilead to work with Ferozons Labs to make and export Remdesivir. Gilead has also contracted with four labs in India.
https://www.voanews.com/covid-19-pandemic/pakistan-set-make-export-anti-covid-19-drug-remdesivir

Partial lockdown is lifted

Public transport remains shut. 

Schools and large shopping malls remain shut.

Factories and offices have opened.

Further relaxation starting in a few days.

What is new for HCQ, AZ, Zinc, Remdesivir, etc?

Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients
https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1

Another study trying to discredit the hydroxychloroquine, studies chloroquine instead:
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765499

A study of HCQ with Zinc in Military Healthcare Workers
https://clinicaltrials.gov/ct2/show/NCT04377646
Completing on July 31 2020

BCG Vaccine is not valuable study
https://jamanetwork.com/journals/jama/fullarticle/2766182

COPD, Asthma, and COVID-19

https://www.aaaai.org/conditions-and-treatments/library/asthma-library/covid-asthma

RESPIRATORY ALLERGIES AND ALLERGIC ASTHMA MAY HAVE PROTECTIVE MECHANISM IN COVID-19

https://www.med.wisc.edu/news-and-events/2020/april/allergies-asthma-may-reduce-covid-19-risk-/

Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2

https://www.sciencedirect.com/science/article/pii/S0091674920305510

Molecular Diagnosis of Allergy: The Pediatric Perspective

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768979/

Vitamin D

My opinion is that you keep the correct levels of vitamin D in your body. Now a days, due to staying indoors, it is possible that you will develop the deficiency of vitamin D. Get this checked by your doctor and use the correct dose to stay healthy.

Here are my notes:

Daily 10 microgram or 400 IU/Day

Lippincott’s Biochemistry Review 4th Edition. Page 388

Daily 5 mg of cholecalciferol or 200 IU of Vitamin D.

However, 800 IU/Day is shown to reduce the incidence of osteoporotic fractures.

800 IU/Day recommended by the Institute of Medicine to maintain bone health.

Frank deficiency is when the levels of 25-hydroxycholecalciferol (25OHD) is less than 20 ng/mL (50 mmol/L)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305614/

No consensus that the oral vitamin D supplements are helpful

Ergocalciferol from plants is called Vitamin D2

Cholecalciferol from the animal tissue is called Vitamin D3

7 deidro-cholesterol to (UV light) to cholecalciferol (D3) to 25 hydroxylase in liver to 25 OH D to -hydroxycholecalciferol 1-hydroxylase in kidney to 1,25 DiOH D3

Vitamin D Receptors are abbreviated to VDR in the notes. These are cytosolic receptors.

https://www.newscientist.com/article/2121424-vitamin-d-supplements-may-prevent-millions-of-winter-infections/

Deficiency of vitamin D makes people more susceptible to respiratory tract infections.

Vitamin D supplement can reduce these infections by 12% 

Keep in mind, this is for those who are deficient in this vitamin. If you are not deficient, then it will not make a difference. Because, you are already good.

Evidence is not sufficient to say that vitamin D helps prevent respiratory infections.

2018 Study

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305614/

People with autoimmune diseases commonly have hypovitaminosis D

What are cathelicidins?

https://www.sciencedirect.com/topics/neuroscience/cathelicidin

What are beta defensins?

https://en.m.wikipedia.org/wiki/Beta_defensin

2011 Study

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166406/

Activation of TLR and PAMPs on macrophages increases the production of 1, alpha hydroxylase and the VDR. This in turn causes more production of cathelicidine and beta defensins 4.

Vitamin D also affects monocytes to reduce production of IL1, IL6, IL8, IL12, and TNF. Regulating the immune response.

Vitamin D acts on the dendritic cells to inhibit/reduce their differentiation and maturation. It reduces their MHCII expression, co-stimulatory molecules like CD40, CD80, CD86, decreased production of IL-12 etc.

2013 Study

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756814/

Vitamin D improves immune system by helping produce cathelicidine and by helping modulate inflammatory cascade. Especially for the respiratory infections.

It also helps produce NFk-B (nuclear factor kappa light chain for activated B cells.)

(

Notes about the NFkB

https://en.wikipedia.org/wiki/NF-%CE%BAB

Helps with cytokine production and cell survival.

NFk-B factor becomes active when T and B cell receptors become active. Its activation causes the gene expressions that allow T cell development, maturation, and proliferation.

T and B cells have Vitamin D receptors that help them produce NFk-B

)

Continuing the notes from the study:

In pulmonary infections. Lung epithelial cells are able to convert inactive vitamin D to its active form. This active Vitamin D then helps produce cathelicidine. Which helps kill the pathogens.

Vitamin D seems to favor TH2 and TH17 cell activation which is anti-inflammatory profile. 

Vitamin D seems to reduce the activation of TH1 cells which are pro inflammatory by their IFN-gamma action.

A deficiency of vitamin D may dysregulate the inflammatory response of the body.

Vitamin B also increases the IkBa. This leads to inhibition of NFkB. This helps reduce the production of IL6 and IL8 by inhibiting the production of NFkB.

A test image

Passive antibody therapy

Antibodies are gamma globulin proteins that make up 20% of the plasma proteins.

Immunoglobulins can be induced actively in the host (through vaccines for example), or acquired passively from other people’s plasma that have the needed antibodies.

1 person may donate plasma that will be useful for about two doses of treatment for COVID-19. It is not sufficient. So, the process is slow.

Passive immunity is used to neutralize toxins of diphtheria, tetanus, botulism. We also have passive antibodies for viruses like rabies, hepatitis A and B viruses, etc.

Plasma contains fibrinogen (for clotting) and albumin (to keep plasma in the blood vessels.) Plasma transports proteins, nutrients, antibodies, etc. to the tissues of the body. Plasma will also wash away the waste products produced by the cells.

Serum on the other hand is plasma minus the clotting factors. Serum is obtained after blood clotting. Serum contains the antibodies, hence one of its use is to test for antibodies.

Antibodies are IgG, IgM, IgA, IgD, and IgE (GAMED)

Immunoglobulins (Igs) act to neutralize the toxins. They help opsonize the pathogens. Activate complement system. And, they help prevent the attachment of the pathogens to mucosal surfaces.

Monoclonal vs. polyclonal antibodies.

Immunoglobulins are glycoproteins. They consist of a light (L) chain, and a heavy (H) chain. Simplest antibody molecule is a Y shaped complex.

Light chains’ heavy region can be either kappa or lambda. But, in one molecule of an immunoglobulin only one type of light chain will be present (either containing kappa or lambda.)

Light chains have one variable and one heavy domain.

Heavy chains have one variable and three or four heavy domains. IgG and IgA have 3, IgM and IgE have 4.

Variable regions of both the chain are for the antigen binding.

Constant region of the heavy chain is for the biological functions like binding to a cell/surface and complement activation.

GM makes classic cars. IgG and IgM activate complement.

IgG looks pregnant. It passes through the placenta.

IgA is always away to the outdoors. It sits in the surface mucosal fluids.

IgD is only a receptor on the B cells.

IgE is on the mast cells and takes parts in allergies. We don’t want too much of this unless there are worm infections.

IgG also helps opsonize (see it has a pac man like open mouth? Phagocytes have receptors for the IgG heavy chains.)

IgM can activate complement. Which in turn produces C3b which is also a opsonizing molecule. Because phagocytes also have the receptors for C3b.

IgM is usually found as five molecules joined with a J chain. Hence, it has ten binding sites (two sites on each protein.) It is the most efficient immunoglobulin and is produced as the first response.

Genes to form the heavy chains are arranged as (VVVV-D-JJJJ-HMHDHGHEHA)

Genes to form the light chains are arranged as (VVVV-D-JJJJ)

All B cells first produce IgM and IgD. Then the class switching allows them to produce IgG, IgE, and IgE. Various cytokines can influence the switching to various Immunoglobulin types.

Once a specific heavy chain has been spliced out, that immunoglobulin cannot be made any more by this B cell.

Every new encounter with the antigen improves the response. This is because of somatic hypermutation and affinity maturation.

FDA approves blood plasma therapy

https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/revised-information-investigational-covid-19-convalescent-plasma

FDA has a form 3926 to fill and send. Response within 4 to 8 hours.

Emergency response needed, call operations at 1-866-300-4374 to seek verbal authorization.

https://www.uscovidplasma.org/

FDA will send an IND number (investigational new drug number.)

https://youtu.be/dZ0xDq7UlD8

First patient to receive plasma in Colorado is a doctor (Dr. Michael Leonard)

https://youtu.be/VvE9TuwbVDo

Mt. Saini

Dr. Jeffery Jhang. Using plasma infusion.

https://youtu.be/4UrigBGv-Q8

Mayo clinic

https://youtu.be/97XVn-PxAxY

Dr. Michael Joyner

https://youtu.be/sBHlCYIj3Cw

Takeda pharma making this product

https://youtu.be/T5vAln2X_YM

A science journalist's take

https://youtu.be/oFZwE6azptM

Global mutation tracker

https://nextstrain.org/ncov/global?l=clock

https://www.theguardian.com/world/2020/apr/06/when-will-coronavirus-vaccine-be-ready

Strategies

a) Weekend form of the virus. For example after heat treatment. Risk is that the virus can become viable again in the host and make them sick.

Examples: 

Viruses: Polio, measles, mumps, rubella, influenza, rotavirus, etc. 

Bacteria: BCG (tuberculosis)

(Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854212/)

Bacterial or viral vectors can be used with antigenic gene inserted in them. BCG bacteria and Adenovirus are used commonly.

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854212/

b) Inactivated

https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/how-are-vaccines-made

c) Another strategy is to make a recombinant vaccine by creating large quantities of the S protein of the virus.

Hepatitis B vaccine is recombinant. (yeast cells used.)

Human papilloma virus vaccine is also recombinant. (produced in yeast or insect cells.)

Aluminum salt is given as an adjuvant.

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854212/

d) Make a vaccine from the viral messenger RNA mRNA.

CureVac site about the mRNA vaccine

https://www.curevac.com/covid-19

Reference video

https://www.youtube.com/watch?v=EZhUuAeN-LE

Excerpt

With our mRNA technology, we instruct the human body to activate its own defense mechanism. To that, we use the natural messenger substance mRNA that contains the construction manual needed to produce proteins. We program this messenger substance with the information about one protein of the coronavirus and inject it into the human body. The body recognizes the protein produced by our cells as something unknown and activates its immune cells to produce antibodies and T-cells against it. In this way, we imitate the natural viral infection and activate the endogenous defense system.

Vaccine making progress

https://www.sciencedirect.com/science/article/pii/S1074761320301205

New England journal of medicine

https://www.nejm.org/doi/full/10.1056/NEJMp2005630

Excerpt

Even with novel platforms, SARS-CoV-2 vaccine development poses challenges. First, although the virus’s spike protein is a promising immunogen for protection, optimizing antigen design is critical to ensure optimal immune response. Debate continues over the best approach — for example, targeting the full-length protein or only the receptor-binding domain.

Exacerbation of lung disease is a concern.

Potential duration of immunity is not known yet.

Coronavirus vaccine might be faster to develop because of its similarities to SARS-COV AND MERS-COV

https://www.theguardian.com/world/2020/apr/06/when-will-coronavirus-vaccine-be-ready

Excerpt

Sars-CoV-2 shares between 80% and 90% of its genetic material with the virus that caused Sars – hence its name.

Lipid nanoparticles to deliver mRNA inside the cells

https://www.ncbi.nlm.nih.gov/pubmed/30788952

A good video for the attenuation process

https://youtu.be/VnrJZ2_YZvE 

A good video for recombinant technique

https://youtu.be/5ffl-0OYVQU

Cancer and COVID-19 Patients

CDC Guidance for people at higher risk of serious illness

https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-risk.html

Takeaways of the cancer discussion

• Most  common cancers among patients are lung (20.95%), git (12.38%), breast (10.48%), thyroid (10.48%), and hematological (8.57%).
• Worst outcomes were for the lung cancers (33.33% CFR) and the hematological cancers (18.18% CFR.)
• Incidence of COVID-19 in cancer patients is high 0.79% vs 0.37% COVID-19 rate.
• Prevalence of cancer in COVID-19 patients is 2%. Prevalence of cancer in general population is 0.29%.
• Hematological cancer patients had a case rate of 10% for COVID-19 compared to less than 1% case rate in non-hematological cancer patients.
• Hematological cancers have 37% CFR vs. 25% CFR in patients with solid tumors.
• Immune system cancer patients did not have increased risk of getting CVOID-19 compared to other hematological cancer patients.
• Cancer patients have weak immune systems.
• Cancer patients with recent (within the last month) procedures/chemo have a higher risk of COVID-19 complications.
• Prevention should be aggressive.
• Elective procedures should be delayed if possible.
• Treatment should be intense and early for cancer patients.
• ICU admission increases the risk of contracting COVID-19

Liang et., al

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30096-6/fulltext

Highlights:

1. 2007 cases from 575 hospitals
2. Cancer patients have a higher risk of developing COVID-19 compared to other individuals.
3. Patients with cancer had poorer outcomes compared to non-cancer patients of COVID-19
4. More patients with SARS-COV-2 get multiorgan organ failure compared to SARS-COV and MERS-COV 
5. Caners patients are at a higher risk of getting infections because of the weak immune system due to the cancers and the cancer treatment.
6. 1% of the COVID-19 patients in this study had cancer. This is higher than 0.29% of the cancer patients in general population. 3x higher prevalence.
7. 28% had lung cancers. The highest cancer type with COVID-19.
8. 25% of the cancer and COVID-19 had received chemotherapy or surgery within the last one month.
9. Patients with lung cancer did not have a higher probability of severe events compared to other cancers (see below for the definition of the severe event.)
10. 25% were cancer survivors.
11. Cancer patients deteriorated more rapidly than non-cancer COVID-19 patients.

Compared to patients without cancers

1. Cancer patients were older mean age 63.1 y, vs. 48.7 y.
2. More likely to have a h/o smoking 22% vs 7%
3. Had more severe baseline CT manifestations. 94% vs 71%
4. No difference in sex, other baseline symptoms, or other comorbidities.
5. Patients with cancer had a higher risk of severe events e.g. invasive ventilation need, or death. 39% vs 8%

Cancer patients with chemo or surgery within the last one month vs no such procedure

1. Higher risk of severe event 75% compared to 43%

Suggestions

1. If possible postpone elective surgeries and chemotherapy (stable cancer.)
2. Stronger personal protection measures are needed in the cancer patients.
3. More intense surveillance and treatment needed in the cancer patients with covid-19.

Dai et., al

Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak

https://cancerdiscovery.aacrjournals.org/content/early/2020/04/24/2159-8290.CD-20-0422

Highlights:

1. 105 cancer patients with COVID-19 were enrolled. Control group was 536 non-cancer COVID-19 patients 
2. 11.43% death rate in patients with cancer compared to 3.8% in patients without cancer.
3. Death rate:
   1. Hematological cancers: 33.33%
   2. Lung cancers: 18.18%
   3. Patients with metastatic cancers had high risk of death: 95%

He et., al

COVID-19 in persons with haematological cancers

https://www.nature.com/articles/s41375-020-0836-7.pdf

1. 128 hospitalized cancer patients and 226 healthcare workers.
2. 10% of the cancer patients developed COVID-19
3. 7% of the healthcare workers developed COVID-19
4. Patients with hematological cancers had a CFR of 62% compared to 0 in the healthcare workers that had COVID-19.
5. Hematological cancer patients had a case rate of 10% for COVID-19 compared to less than 1% case rate in non-hematological cancer patients.
6. Hematological cancers have 37% CFR vs. 25% CFR in patients with solid tumors.
7. Immune system cancer patients did not have increased risk of 

American Society of Clinical Oncology

https://www.cancer.org/latest-news/common-questions-about-the-new-coronavirus-outbreak.html

COVID-19 Increases Overall Risk of Death, Complications in Patients With Cancer, Study Shows

(They refer Dai et., al study noted above.)

https://www.ajmc.com/newsroom/covid19-increases-overall-risk-of-death-complications-in-patients-with-cancer-study-shows

SARS-COV-2 Monoclonal Antibodies

Human antibody against SARS-COV-2
Monoclonal antibodies
https://en.wikipedia.org/wiki/Monoclonal_antibody

A human monoclonal antibody blocking SARS-CoV-2 infection
https://www.nature.com/articles/s41467-020-16256-y

Antibody blocks infection by the SARS-CoV-2 in cells, scientists discover
https://www.sciencedaily.com/releases/2020/05/200504074722.htm

Israeli scientists discover monoclonal antibody that neutralizes SARS-CoV-2
https://www.google.com/amp/s/www.news-medical.net/amp/news/20200505/Israeli-scientists-discover-monoclonal-antibody-that-neutralizes-SARS-CoV-2.aspx

https://www.sciencedirect.com/science/article/pii/S1471490620300570

https://www.medrxiv.org/content/10.1101/2020.04.06.20055475v1

https://www.nature.com/articles/s41423-020-0426-7

Natural Killer (NK) Cells and SARS-COV-2

https://erj.ersjournals.com/content/early/2020/03/26/13993003.00749-2020
Children have a high number of NK cells
Lymphocytes are also higher in children due to frequent infections.
Children’s immune system also offers cross-reactivity to other viruses (for example measles vaccine offers immune training to have cross-reactivity to other pathogens.)

——
Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4+ T Cells Are Important in Control of SARS-CoV Infection
https://jvi.asm.org/content/84/3/1289 

———
http://lvts.fr/Pages_html/Encyclopedies/FundamentalImmunology/ramiCOMMAND=applyStylesheet(interface.xsl,pau@CH012S0402.pub)&p_userid=pau.html
Excerpt
Hence, in viral infections, NK cells are thought to play a central role primarily in the early stages of the response, in which they function to restrain viral replication until the adaptive immune response is sufficiently developed to control the infection.
 Studies of mice with a mutation in the perforin gene demonstrated that perforin-dependent cytotoxicity plays an important role in controlling MCMV replication in the spleen but little or no role in the liver (172,173).

Important: NK cells are useful in the early stage of the infection by reducing the replication and giving a chance to the adaptive arm to become ready.

————
Functional exhaustion of antiviral lymphocytes in COVID-19 patients
https://www.nature.com/articles/s41423-020-0402-2?proof=trueIn%25EF%25BB%25BF

We showed that the total number of NK and CD8+ T cells was decreased markedly in patients with SARS-CoV-2 infection. The function of NK and CD8+ T cells was exhausted with the increased expression of NKG2A in COVID-19 patients. Importantly, in patients convalescing after therapy, the number of NK and CD8+ T cells was restored with reduced expression of NKG2A. These results suggest that the functional exhaustion of cytotoxic lymphocytes is associated with SRAS-CoV-2 infection. Hence, SARS-CoV-2 infection may break down antiviral immunity at an early stage.

——

Mechanism of NK cells exhaustion
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487399/

multiple mechanisms might contribute to the exhaustion of NK cells, such as dysregulated NK cell receptors signaling, as well as suppressive effects by regulatory cells or soluble factors within the microenvironment. 

——

CD107+ NK Cells
https://www.ncbi.nlm.nih.gov/pubmed/15604012

——

NKG2A/CD94 receptors complex
https://www.cell.com/cell/fulltext/S0092-8674(18)31573-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867418315733%3Fshowall%3Dtrue

——

Natural Killer Cells: Development, Maturation, and Clinical Utilization
https://www.frontiersin.org/articles/10.3389/fimmu.2018.01869/full

——

IFN gamma is produced by NK Cells, CD4H1, and CD8 Cytotoxic
https://en.wikipedia.org/wiki/Interferon_gamma

https://pubmed.ncbi.nlm.nih.gov/15080302/

https://clinicaltrials.gov/ct2/show/NCT04280224

https://www.cryo-cell.com/blog/february-2020/is-there-potential-for-cord-blood-nk-cells-to-treat-cancer-and-coronavirus

Remdesivir Mechanism of Action

Note: Remdesivir is an adenine analog and not uracil. I taught it as a Uracil analog.

MERS-COV peaks in humans between 7-10 days after the onset of symptoms. This gives a good chance to use Remdesivir.
Early therapy with Remdesivir will help reduce the virus load and the damage due to the immune response.
https://www.nature.com/articles/s41467-019-13940-6
https://www.ncbi.nlm.nih.gov/pubmed/28659436

Mechanism of action
https://microbenotes.com/remdesivir/

Adenosine nucleotide analog

SARS-COV and MERS-COV pathophysiology
https://www.mdpi.com/1999-4915/11/1/59/htm

Clinical Trial of Remdesivir to Treat COVID-19 Begins
https://www.niaid.nih.gov/news-events/nih-clinical-trial-remdesivir-treat-covid-19-begins

The improvement observed in 68% of the patients
https://www.nejm.org/doi/pdf/10.1056/NEJMoa2007016?articleTools=true

Remdesivir clinical trials
https://www.gilead.com/purpose/advancing-global-health/covid-19/remdesivir-clinical-trials

Inconclusive yet hopeful results
https://www.biospace.com/article/data-from-gilead-s-compassionate-use-of-remdesivir-for-covid-19-looks-promising/

Another study finds the drug with a high death rate and more side effects
https://www.ft.com/content/0a4872d1-4cac-4040-846f-ce32daa09d99

Renin increases when the blood volume reduces. I said the other way.

Case fatality rates and comorbidities

New York
https://jamanetwork.com/journals/jama/fullarticle/2765184

https://www.cebm.net/covid-19/global-covid-19-case-fatality-rates/

Chinese data till February 11th, 2020
Case fatality rate (CFR)
Cardiovascular diseases: 10.5%
Diabetes: 7.3%
Chronic respiratory diseases: 6.3%
Hypertension: 6%
Cancer: 5.6%

Italy’s percentage of death with comorbidities out of 355 deaths studied:
https://www.epicentro.iss.it/coronavirus/bollettino/Report-COVID-2019_17_marzo-v2.pdf
HTN: 76%
DM: 36%
IHD (ischemic heart disease): 33%

https://www.nature.com/articles/s41569-020-0360-5?fbclid=IwAR3TjvxiEtYQqNkpsPuEuuef94Gp2m4a89YFxubY2pw2FtOxsSpxGZ18TmI



https://www.ahajournals.org/doi/10.1161/JAHA.120.016219

ACE2 expression in the heart is lesser than intestine but more than lungs
ACE2 expression increased in cardiac failure
https://academic.oup.com/cardiovascres/article/116/6/1097/5813131


15-30% of the COVID-19 patients have HTN
2.5-15% of the COVID-19 patients have heart disease

Angiotensin receptors
https://en.wikipedia.org/wiki/Angiotensin_II_receptor

Angiotensin 1-7
https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.113.01274


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118626/

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30079-5/fulltext?utm_source=sootoday.com&utm_campaign=sootoday.com&utm_medium=referral

Cardiac troponin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770452/

Note, the healthcare burden is only assessed for the patients that need oxygen or ventilation. We did not assess the massive amount of testing needs, and the other medical resources that are needed.

As the COVID-19 pandemic continue to unfold, we see a lots of countries, cities, and territories that are grossly underestimating the risk facing them. China did a brilliant job in Wuhan to contain the situation. They built new hospitals, locked down the city early on. Aggressively tested and managed. Compare that to the response in the countries with large populations like the USA, India, Pakistan, etc.

Look at the mess in Italy. They are having to make moral decisions for which patients to let die because they do not have enough ventilators.

In this talk, we will discuss possible healthcare system needs for the serious and critical patients in the city of NY, Lahore, and New Delhi. We hope that we are wrong and the outcome is lesser than what we project, however, we feel that the actual outcome will be 10x more than what we have projected in this talk.

Any issues with the data, or the analysis? Reach out to us, we will be happy to adjust and modify to make better sense of this information.

Need access to the calculator, let us know and we will be happy to share.

Stay safe, stay healthy, stay clean.

In this talk Dr. Mobeen discusses the case fatality rate (CFR) of COVID-19 by SARS-COV-2, and also compares it to the flu's CFR.

Following topics are covered:

• Definition of case fatality rate (CFR)
• Limitations of the data used
• How rapidly is the virus spreading?
• Types of the COVID-19 cases
• Mortality risk vs. confirmed deaths
• COVID-19 stages
• Statistics by age, gender, and comorbidities
• Comparison of the COVID-19 CFR with flu CFR

ACE2 Enzyme and COVID-19 Hypercoagulability - Part 1

Generation of Ang 1-7
https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.113.01274


Ang (1-7) receptors (MAS Receptors)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC166216/

MAS Receptor history and the reason for its name
https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.118.10918

Ang (1-7)
Angiotensin-(1–7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2- and NF-κB-dependent pathways
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402818/

What is superoxide radical?
https://en.wikipedia.org/wiki/Superoxide

Vasoconstriction by Angiotensin II
Cellular Mechanism of Vasoconstriction Induced by Angiotensin II
It Remains To Be Determined
https://www.ahajournals.oxidase

Let's discuss the first COVID-19 case in the USA.


Link to the study
https://www.nejm.org/doi/full/10.1056/NEJMoa2001191

Is the venous lactate similar to arterial lactate
https://acutecaretesting.org/en/journal-scans/arterial-versus-venous-lactate

Role of interleukin 1
https://en.wikipedia.org/wiki/Interleukin-1_family

Acute-phase proteins. Pay attention to positive and negative proteins.
https://en.m.wikipedia.org/wiki/Acute-phase_protein


Specimen collection guidelines by FDA
https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fguidelines-clinical-specimens.html

Procalcitonin levels
https://en.wikipedia.org/wiki/Procalcitonin
https://labtestsonline.org/news/fda-clears-procalcitonin-test-for-new-use-to-help-guide-antibiotic-treatment

Hypertension and SARS-COV-2

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area
https://jamanetwork.com/journals/jama/fullarticle/2765184
https://cdn.jamanetwork.com/ama/content_public/journal/jama/0/joi200043supp1_prod.pdf?Expires=2147483647&Signature=A5tsOPF-GMnuTMtbUBElyqb143MA-AyWRwfE60PY96nmwzs1HC38FFtE9fvBzyNRMgWuPXkTx2SQ8D43oA2~uB~J6j94E9AFWW2HcbhurpiTTl0sG-tpezMQXdWpfCQ30O-tM5ga3LV3DmTFoOAZeZ3mbjoa7U6FnT5k8KRCiGfe8usXWxOkfRz~YbzyHgizF0HEs-tGud6zf38rFnkrKXs5wBdHJwhrnrl6zWxaspd5L4WEpuL05ka5z9N2ia0ehvopWgZTdrQWdLxzVtjaR0xQ4dA5rwB2LpDJ5x8VnjCF8fF2~mOR5vkSyOMMX8wQnR278dQcCs7zKcWEIwUhfA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA

Hypertension and COVID-19
https://academic.oup.com/ajh/advance-article/doi/10.1093/ajh/hpaa057/5816609

A crucial role of angiotensin-converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury
https://www.nature.com/articles/nm1267
 

Correction: read TH1 as TH2 and vice versa. I mistakenly switched them. 

BCG Vaccine and SARS-COV-2 (COVID-19)

Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study
https://www.medrxiv.org/content/10.1101/2020.03.24.20042937v1

How does BCG Vaccine work?
https://www.nhs.uk/conditions/vaccinations/bcg-tb-vaccine-questions-answers/

BCG Vaccine trials
https://www.newsweek.com/scientists-boston-australia-netherlands-trial-bcg-vaccine-covid-19-who-1498069

The trial in the Netherlands
https://clinicaltrials.gov/ct2/show/NCT04328441

Massachusetts
https://www.faustmanlab.org/wp-content/uploads/2020/04/BCG2-pagerC-19.pdf

Trained Immunity
https://science.sciencemag.org/content/352/6284/aaf1098

CD4+ Cell Memory created by BCG
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679806/

Response to mycobacterium TB (Mtb) 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298253/
Cytotoxic response

https://www.livescience.com/coronavirus-protection-using-tuberculosis-vaccine.html

WHO
https://www.who.int/news-room/commentaries/detail/ Bacille-Calmette-guérin-(BCG)-vaccination-and-COVID-19

BCG and melanoma treatment
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1344159/

BCG and Type 1 DM
https://www.ncbi.nlm.nih.gov/pubmed/30600132

BCG and bladder cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411413/

https://www.novinite.com/articles/204095/Countries+with+Mandatory+Policies+to+BCG+Vaccine+Register+Fewer+Coronavirus+Deaths

Mobeen’s thoughts
Objectives:
Resume the daily life, economic cycle, while keeping the virus spread low.

https://www.google.com/amp/s/qz.com/1844946/south-korea-keeps-social-distancing-post-covid-19-containment/amp/


https://youtu.be/TwyQfEg2amM


https://youtu.be/Q_VFK-9aYYA



https://youtu.be/rhtXA-_1pvM


Hong Kong, Taiwan, South Korea Buck Global Lockdown Trend
https://www.japantimes.co.jp/news/2020/04/08/asia-pacific/hong-kong-taiwan-south-korea-buck-global-lockdown-trend/#.XqN0r1NKijI

South Korea … A model for others to follow?
https://english.alarabiya.net/en/features/2020/04/03/South-Korea-conquered-coronavirus-without-a-lockdown-a-model-to-follow-

Diabetes and COVID-19

Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China
https://jamanetwork.com/journals/jama/fullarticle/2762130

Chinese data till February 11th, 2020
Case fatality rate (CFR)
Cardiovascular diseases: 10.5% 
Diabetes: 7.3%
Chronic respiratory diseases: 6.3%
Hypertension: 6%
Cancer: 5.6%

Prevention steps to stay healthy
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fprepare%2Fprevention.html

Diabetic patients are
More prone to dehydration due to elevated glucose. (As the kidneys throw the glucose out and in the process throw the water out as well.) So keep it controlled.
When A1C goes in 9-10 range then the risk of complications increases significantly.

What to do?
Wash hands
Wear mask
Get a flu shot
If you are insulin dependent then keep extra insulin at hand.
Keep your diabetes and hypertension well managed.

What happens to immune system in diabetes?
https://www.ncbi.nlm.nih.gov/pubmed/19069085

https://www.researchgate.net/post/What_is_cause_of_immunosupression_in_diabetes_melitus

Chronic hyperglycemia causes blood vessel narrowing and damage leading to slower perfusion and nerve damage. Nerve damage occurs both because of poor blood supply to the nerves and the accumulation of glucose in the myeline sheath and damaging it. 

High glucose levels impair neutrophil activity (innate arm.)
Cytosolic calcium increases in PMN cells. This in turn reduces their ability to phagocytose. It happens because high levels of calcium reduce the synthesis of ATP that in turn is needed for the cellular function.
Study showing that the hyperglycemia increases intracellular calcium: https://www.ncbi.nlm.nih.gov/pubmed/9387128

PMN chemotaxis is also impaired.
Reduced complement response
Reduced leukocyte adherence to the blood vessels. Study mentioning endothelial dysfunction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348526/
Reduced response to pathogens
Chronic hyperglycemia leads to acidosis which further reduces the activity of the immune system. (Study mentioning immune dysregulation with various acids: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1065014/)
Skin cells become less efficient and skin and urinary infections become common.

Additionally, the reduced carbohydrate metabolism causes increased fatty acids mobilization. This results in the vascular endothelium to become atherosclerotic. Resulting also, in the narrowing of the blood vessels and reduced perfusion.
High free fatty acids also cause high levels of reactive oxygen species. This in turn makes our tissues prone to easy damage.
FFA cause disruption of insulin responding mechanisms.
Inflammation caused by ROS leading to adipocyte insulin resistance and inflammation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995181/

Hyperglycemia causes an increase of dicarbonyl production. Dicarbonyl in turn reduces the function of beta-definsins. That are necessary to kill pathogens.

Endocrine and metabolic link to coronavirus infection
https://www.nature.com/articles/s41574-020-0353-9

MERS COV and diabetes
Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection
https://insight.jci.org/articles/view/131774

T Helper 17 cells that release IL-17alpha
https://en.wikipedia.org/wiki/T_helper_17_cell

Transforming growth factor beta (TGF-β), interleukin 6 (IL-6), interleukin 21 (IL-21) and interleukin 23 (IL-23) contribute to Th17 formation in mice and humans.

Vitamin D in turn severely impairs the production of the TH17 cells. Hence, reducing the proinflammatory behavior.

ACE2 activity is upgregulated in pancreas of the diabetic patients.
https://www.mdpi.com/1422-0067/18/3/563

Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes
https://link.springer.com/article/10.1007/s00592-009-0109-4

Why Is Coronavirus a Bigger Worry for People With Diabetes?
https://www.medicinenet.com/script/main/art.asp?articlekey=230197

Everything You Should Know About Coronavirus and Diabetes
https://www.healthline.com/diabetesmine/coronavirus-and-diabetes

https://www.diabetes.org/covid-19-faq
Are people with diabetes more likely to get COVID-19?

How about DKA and complication?

What are the concerning signs?
Shortness of breath
Persistent pressure/pain in the chest
New confusion or inability to arouse
Bluish lips/tongue or face

High blood sugar means that cells have less sugar to function. This includes the immune cells. Hence, all cells become an easy target.

Calcium depletion in the presence of hyperglycemia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639077/

Note: I meant to say increase pH does not decrease pH. 

HCQ: 
Reduces virus fusion with the cell membrane.
Causes a basic cellular environment that reduces virus replication
Allows Zinc to enter the cell.
Changes the glycation of the ACE2 receptor making its binding affinity less for the SARS-COV-2

This is why Astragalus is having excellent results in China to prevent and weaken Covid19...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729712/

Dr. Gautret
https://www.ncbi.nlm.nih.gov/pubmed/32205204

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
https://www.sciencedirect.com/science/article/pii/S0924857920300996

No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection
https://www.sciencedirect.com/science/article/pii/S0399077X20300858?via%3Dihub#bib0055

Chinese study
https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3

Ongoing studies

NYU
https://www.cnbc.com/2020/04/15/coronavirus-us-clinical-trials-of-hydroxychloroquine-hit-warp-speed.html

ORCHID
https://clinicaltrials.gov/ct2/show/NCT04332991

PATCH Trial
https://clinicaltrials.gov/ct2/show/NCT04329923

Asymptomatic Cases of SARS-COV-2

Asymptomatic kids
Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30198-5/fulltext
36 children. All were identified to be infected with severe acute respiratory syndrome coronavirus 2

Asymptomatic (ten [28%]) or 
had acute upper respiratory symptoms (seven [19%]).

COVID-19 Antibody Seroprevalence in Santa Clara County, California
https://www.medrxiv.org/content/10.1101/2020.04.14.20062463v1

Their disclaimer
This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

The total population of the county is 1.9M

On the sample date, the 3rd and 4th of April confirmed coronavirus cases in Santa Clara County were around 1,100. This is 0.05% of the population

Tested antibodies to SARS-COV-2 in the serum.
3,330 people
The population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%).
These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April
50-85-fold more than the number of confirmed cases.

Coronavirus spread: Number of people infected by COVID-19 maybe 50-80 times higher than the official count, Stanford study suggests
https://abc7news.com/stanford-coronavirus-study-number-people-infected-by-santa-clara-county-total-covid-19/6110894/

GERMANY TO INTRODUCE CORONAVIRUS 'IMMUNITY CERTIFICATES' FOR RECOVERED PUBLIC
https://www.newsweek.com/germany-antibodies-tests-general-public-immunity-certificates-1494934

healthy/asymptomatic cases
NIH begins study to quantify undetected cases of coronavirus infection
https://www.nih.gov/news-events/news-releases/nih-begins-study-quantify-undetected-cases-coronavirus-infection
SARS-COV-2 Antibody tests begin for understanding the seroconversion in 

UC Berkeley to test 5,000 healthy people in East Bay for coronavirus
https://www.sfchronicle.com/health/article/UC-Berkeley-launches-study-to-test-5-000-healthy-15206367.php
Over eight months, the researchers will conduct rounds of diagnostic tests using nasal swabs to identify infections. And they will take saliva and blood samples to look for antibodies, which would indicate that such people had had COVID-19 and recovered — perhaps without ever realizing they’d been infected with the coronavirus.

Presymptomatic Transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020
https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e1.htm?s_cid=mm6914e1_w

Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility — King County, Washington, March 2020
https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e1.htm

You May Be Infected With Coronavirus and Not Know It
https://health.usnews.com/health-care/patient-advice/articles/asymptomatic-coronavirus-carriers-what-you-need-to-know

25% of the infected may be asymptomatic

CDC Director On Models For The Months To Come: 'This Virus Is Going To Be With Us'
https://www.npr.org/sections/health-shots/2020/03/31/824155179/cdc-director-on-models-for-the-months-to-come-this-virus-is-going-to-be-with-us

I have been saying this for a long time.

1 in 4 people can be asymptomatic

One of the [pieces of] information that we have pretty much confirmed now is that a significant number of individuals that are infected actually remain asymptomatic. That may be as many as 25%. That's important, because now you have individuals that may not have any symptoms that can contribute to transmission, and we have learned that in fact, they do contribute to transmission.
And finally, of those of us that get symptomatic, it appears that we're shedding the significant virus in our oropharyngeal compartment, probably up to 48 hours before we show symptoms. This helps explain how rapidly this virus continues to spread across the country because we have asymptomatic transmitters and we have individuals who are transmitting 48 hours before they become symptomatic.

Pediatrician says 80% of kids likely have coronavirus, but they're so asymptomatic you'd never know
https://www.cbsnews.com/news/coronavirus-children-pediatrician-80-percent-asymptomatic/
Children are asymptomatic, mildly symptomatic, or note tested. But they are spreading the virus.

SARS-COV-2 Reinfection

We need to know the following to follow this talk
What is reinfection?
What is reactivation?
What is a carrier?
What is a false negative?
What is a false positive?
What is the sensitivity of a test?
What are immunoglobulins? 
What is the role of IgM, IgG, and IgA?
What is seroconversion?
What is class-switching?
How long do the memory B cells live?

Notes
Immunoglobulins are formed from the day 7-10. First IgM and then IgG. (In case of SARS-COV-2 N protein, IgG is formed from the day 4th.)
IgA will be formed and sent to live in the mucus membranes.
Immunoglobulins peak near 3 months.
Formed antibodies live from a few weeks to months in the body.
Memory cells are formed in the process that will respond within 24-48 hours when the pathogens arrive in our body again.
New IgG and IgA are formed to combat the virus.
in the case of SARS-COV-1, the antibodies were produced up to 3 years after the recovery.
In rhesus monkeys, the SARS-COV-2 reinfection was not successful.

What can fail our immune system?
1. Weak immune system.
2. Immunosuppression
3. False-negative tests
4. False-positive tests
5. Viral mutation

Immune System Response to SARS-COV-2 is humoral in nature
https://onlinelibrary.wiley.com/doi/10.1002/rmv.2107
IgG against N proteins starts on the day 4
Most patients seroconverting by day 14
Peak specific IgM after 9 days of the infection.
Class switching to IgG in the second week.

Mobeen’s thoughts:
Enough time is not passed to know how long the antibodies will live?
Enough time is not passed to detect how long the memory cells can continue to produce antibodies to the virus?
I will take the standard immune response and say that we will be immune for at least 3 months to 3 years. 3 months considering the existing antibodies. 3 years considering the memory cells.
Reinfection is not possible during the immune phase.
Reactivation is not proved.
Possibly false negative at the time of discharge. Or false positive at the re-test. Or a more sensitive test that can pick up the remnant RNA pieces from the mucus membranes and the cells.
GIT can keep the virus for 50 days after the recovery but is not significant.
Do we have carriers? Folks, that are asymptomatic but allow the virus to shed?

SARS-COV-1 (from 2012-2015) shows that the coronavirus antibodies can be produced for up to 3 years after the recovery.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851497/

Reinfection could not occur in SARS-COV-2 infected rhesus macaques
https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1.full
Excerpt from the study
Importantly, the unsuccessful rechallenge in NHP models suggested that the re-positivity from discharged patients could not be due to reinfection. 

Re-detectable positive RNA test in recovered patients.
https://www.medrxiv.org/content/10.1101/2020.03.26.20044222v1.full.pdf

Maybe the new test was hypersensitive in these RP patients (RP = re-detectable positive)?

The study found that the patients remained asymptomatic, their disease did not progress, and they did not cause infections to others.

Excerpt from the discussion
And from a recent longitudinal study in SARS-CoV-2 infected rhesus macaques, reinfection could not occur in convalescent monkeys [20]. Long-term follow-up of these close contacts with RP patients will warrant the evaluation of the possible risk of RP

It may have been a less sensitive test. 
Excerpt from the study
Our data support the notion that the false negatives using commercial kit may partially account for the RP because the kits had only 30%–50% positive rate of detection 

Maybe the immune response via IgA was not sufficient to clear the virus from the mucus membranes?
Excerpt from the study
Nor could we exclude immunological factors including low mucosal immune responses such as low IgA levels. 

Study where patients were positive after 5-13 days of discharge. They did not have disease progression and they did not make their family members sick.
https://jamanetwork.com/journals/jama/fullarticle/2762452
The study thinks that these folks may be carriers.

Let’s understand the antibodies. Immune cell behavior, and memory cells. Let’s also look at the passive immunity i.e. antibodies given from outside.

Antibodies are produced for about 7-10 days. IgM first and then IgG.

Memory B cells respond within 24-48 hours. (Reference: https://academic.oup.com/occmed/article/57/8/552/1474357)

Passive immunity lasts from a few weeks to months.
https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm
https://en.wikipedia.org/wiki/Passive_immunity
https://academic.oup.com/occmed/article/57/8/552/1474357

https://www.reuters.com/article/us-health-coronavirus-who/who-says-looking-into-reports-of-some-covid-patients-testing-positive-again-idUSKCN21T0F1?il=0

Possibly the virus got reactivated instead of reinfection
http://www.koreaherald.com/view.php?ud=20200412000213&np=3&mp=1

https://time.com/5810454/coronavirus-immunity-reinfection/

Will Summers Help Reduce Coronavirus Infections?

Good article
https://www.advisory.com/daily-briefing/2020/03/26/covid-summer

Tropical temperature is 64F or 18C and above
https://sciencing.com/meaning-tropical-climate-8722483.html

Humidity
https://www.weather.gov/lmk/humidity
Absolute humidity is the amount of water vapor in a cubic meter of the air.
30 grams per cubic meter is maximum

Relative humidity
It is a percentage of the amount of vapor at a specific temperature to the absolute humidity. For a cubic meter, it is
Actual amount/Total amount that air can hold
Warm air can hold more.
Cooler air can hold less

Study in China before containment to see the spread in various cities that had differing temperatures.

March 9, 2020
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3551767&fbclid=IwAR0JQJe3QxYsrP83RUDLsBnjZvLa5hkzoCAEvcsTbyuzI1xEQA8h3U7V7LM

Jan 21 to Jan 23, 2020 (non intervened transmission.)
40 cases

1 degree C increase in temperature lowered R0 by 0.0225
1% increase in humidity lowered the R0 by 0.0158

Excerpt
the virus was more contagious in northern China, where temperatures and humidity were relatively low and less contagious in the warmer and more humid cities in the country's southeast coast.

Temperature, Humidity and Latitude Analysis to Predict Potential Spread and Seasonality for COVID-19
March 5, 2020
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3550308&mod=article_inline

Excerpt
Sajadi said, "It couldn't have been bad luck that these particular places were hit." He explained, "This virus is acting as a seasonal respiratory virus. We could be wrong, but with the data we have, we think that is the most likely scenario."

Will Coronavirus Pandemic Diminish by Summer?
March 17, 2020
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3556998

83% of testing has been in non-tropical countries (30N and above). 
90% of the cases are recorded in the range of 3C to 17C.
72% of the cases are in the areas with humidity between 3 to 9 g/m3.

Most tropical countries have not tested as extensively as northern countries. (Mobeen’s comment: what about China and South Korea? South Korea did a lot of testing. South Korea is 35.90N)

Several countries between 30N and 30S such as Australia, UAE, Qatar, Singapore, Bahrain, Qatar, and Taiwan have performed extensive testing per capita and the number of positive 2019-nCoV cases per capita is lower in these countries compared to several European countries and the US.

Current data, although limited, suggests that it is extremely unlikely that the spread of 2019-nCoV would slow down in the USA or Europe, due to environmental factors, because a large number of cases have already been reported in the range of AH and T experienced by these regions for the most part of the year. 

if, new cases in April and May continue to cluster within the current observed range of AH i.e. 3 to 9g/m3, then the countries experiencing monsoon, i.e. having high absolute humidity (more than 10 g/m3) could see a slowdown in transmissions, due to climatic factors.

Our results in no way suggest that 2019-nCoV would not spread in warm humid regions and effective public health interventions should be implemented across the world to slow down the transmission of 2019-nCoV.

Excerpt
"Wherever the temperatures were colder, the number of the cases started increasing quickly," said Qasim Bukhari, a computational scientist at MIT and a co-author of the study. "You see this in Europe, even though the health care there is among the world's best," Bukhari said.

Warm weather, humidity could curb rapid COVID-19 transmission, study shows

https://www.beckershospitalreview.com/infection-control/warm-weather-humidity-could-curb-rapid-covid-19-transmission-study-shows.html

Coronavirus Outbreaks Could Become Seasonal Woe, Some Researchers Suggest

https://www.wsj.com/articles/coronavirus-outbreaks-could-become-seasonal-woe-some-researchers-find-11584955802

SARS-COV-2 testing

https://www.google.com/amp/s/www.livescience.com/amp/coronavirus-tests-available.html

An example test publication

https://www.fda.gov/media/136786/download

E Gene (envelop)

N Gene (nucleocapsid)

ORF1b of RdRp (open reading frame 1b of the RNA dependent RNA polymerase.)

https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations

https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-diagnostic-testing-sars-cov-2

An example testing company

https://www.fda.gov/media/136786/download

Taqman process

https://en.wikipedia.org/wiki/TaqMan

Polymerase chain reaction

https://en.wikipedia.org/wiki/Polymerase_chain_reaction

Thermal cycler machine

https://en.wikipedia.org/wiki/Thermal_cycler

Overview of ELISA

https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/overview-elisa.html

SARS-COV-2 Attacks 1 Beta Chain of Hemoglobin

https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173

Excerpt

This report demonstrates that the hemoglobin and neutrophil counts of most patients have decreased, and the index values of serum ferritin, erythrocyte sedimentation rate, C-reactive protein, albumin, and lactate dehydrogenase of many patients increase significantly. This trace implies that the patient's hemoglobin is decreasing, and the heme is increasing, and the body will accumulate too many harmful iron ions, which will cause inflammation in the body and increase C-reactive protein and albumin. 

Neutrophil longevity is modulated by heme

https://www.jimmunol.org/content/173/3/2023

Tissues contain porphyrins

https://www.ncbi.nlm.nih.gov/pubmed/8535617

https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/porphyrin

https://www.ncbi.nlm.nih.gov/pubmed/8258382

Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study

https://www.medrxiv.org/content/10.1101/2020.03.24.20042937v1

How does BCG Vaccine work?

https://www.nhs.uk/conditions/vaccinations/bcg-tb-vaccine-questions-answers/

BCG Vaccine trials

https://www.newsweek.com/scientists-boston-australia-netherlands-trial-bcg-vaccine-covid-19-who-1498069

Trial in Netherlands

https://clinicaltrials.gov/ct2/show/NCT04328441

Massachusetts

https://www.faustmanlab.org/wp-content/uploads/2020/04/BCG2-pagerC-19.pdf

Trained Immunity

https://science.sciencemag.org/content/352/6284/aaf1098

CD4+ Cell Memory created by BCG

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679806/

Response to mycobacterium TB (Mtb) 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298253/

Cytotoxic response

https://www.livescience.com/coronavirus-protection-using-tuberculosis-vaccine.html

WHO

https://www.who.int/news-room/commentaries/detail/bacille-calmette-guérin-(bcg)-vaccination-and-covid-19

BCG and melanoma treatment

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1344159/

BCG and Type 1 DM

https://www.ncbi.nlm.nih.gov/pubmed/30600132

BCG and bladder cancer

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411413/

https://www.novinite.com/articles/204095/Countries+with+Mandatory+Policies+to+BCG+Vaccine+Register+Fewer+Coronavirus+Deaths

Asymptomatic kids

Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30198-5/fulltext

36 children. All were identified to be infected with severe acute respiratory syndrome coronavirus 2

Asymptomatic (ten [28%]) or 

had acute upper respiratory symptoms (seven [19%]).

COVID-19 Antibody Seroprevalence in Santa Clara County, California

https://www.medrxiv.org/content/10.1101/2020.04.14.20062463v1

Their disclaimer

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

Total population of the county is 1.9M

On the sample date 3rd and 4th of April, confirmed coronavirus cases in Santa Clara County was around 1,100. This is 0.05% of the population

Tested antibodies to SARS-COV-2 in the serum.

3,330 people

The population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%).

These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April

50-85-fold more than the number of confirmed cases.

Coronavirus spread: Number of people infected by COVID-19 may be 50-80 times higher than official count, Stanford study suggests

https://abc7news.com/stanford-coronavirus-study-number-people-infected-by-santa-clara-county-total-covid-19/6110894/

GERMANY TO INTRODUCE CORONAVIRUS 'IMMUNITY CERTIFICATES' FOR RECOVERED PUBLIC

https://www.newsweek.com/germany-antibodies-tests-general-public-immunity-certificates-1494934

healthy/asymptomatic cases

NIH begins study to quantify undetected cases of coronavirus infection

https://www.nih.gov/news-events/news-releases/nih-begins-study-quantify-undetected-cases-coronavirus-infection

SARS-COV-2 Antibody tests begin for understanding the seroconversion in 

UC Berkeley to test 5,000 healthy people in East Bay for coronavirus

https://www.sfchronicle.com/health/article/UC-Berkeley-launches-study-to-test-5-000-healthy-15206367.php

Over eight months, the researchers will conduct rounds of diagnostic tests using nasal swabs to identify infections. And they will take saliva and blood samples to look for antibodies, which would indicate that such people had had COVID-19 and recovered — perhaps without ever realizing they’d been infected with the coronavirus.

Presymptomatic Transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020

https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e1.htm?s_cid=mm6914e1_w

An example

Cluster B. A woman aged 54 years (patient B1) attended a dinner event on February 15 where she was exposed to a patient with confirmed COVID-19. On February 24, patient B1 and a woman aged 63 years (patient B2) attended the same singing class. Two days later (February 26), patient B1 developed symptoms; patient B2 developed symptoms on February 29.

Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility — King County, Washington, March 2020

https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e1.htm

Conclusion

This analysis suggests that symptom screening could initially fail to identify approximately one half of SNF residents with SARS-CoV-2 infection. Unrecognized asymptomatic and presymptomatic infections might contribute to transmission in these settings. During the current COVID-19 pandemic, SNFs and all long-term care facilities should take proactive steps to prevent introduction of SARS-CoV-2, including restricting visitors except in compassionate care situations, restricting nonessential personnel from entering the building, asking staff members to monitor themselves for fever and other symptoms, screening all staff members at the beginning of their shift for fever and other symptoms, and supporting staff member sick leave, including for those with mild symptoms (3). Once a facility has a case of COVID-19, broad strategies should be implemented to prevent transmission, including restriction of resident-to-resident interactions, universal use of facemasks for all health care personnel while in the facility, and if possible, use of CDC-recommended PPE for the care of all residents (i.e., gown, gloves, eye protection, N95 respirator, or, if not available, a face mask) (3). In settings where PPE supplies are limited, strategies for extended PPE use and limited reuse should be employed (4). As testing availability improves, consideration might be given to test-based strategies for identifying residents with SARS-CoV-2 infection for the purpose of cohorting, either in designated units within a facility or in a separate facility designated for residents with COVID-19. During the COVID-19 pandemic, collaborative efforts are crucial to protecting the most vulnerable populations.

You May Be Infected With Coronavirus and Not Know It

https://health.usnews.com/health-care/patient-advice/articles/asymptomatic-coronavirus-carriers-what-you-need-to-know

25% of the infected may be asymptomatic

CDC Director On Models For The Months To Come: 'This Virus Is Going To Be With Us'

https://www.npr.org/sections/health-shots/2020/03/31/824155179/cdc-director-on-models-for-the-months-to-come-this-virus-is-going-to-be-with-us

I have been saying this for a long time.

1 in 4 people can be asymptomatic

One of the [pieces of] information that we have pretty much confirmed now is that a significant number of individuals that are infected actually remain asymptomatic. That may be as many as 25%. That's important, because now you have individuals that may not have any symptoms that can contribute to transmission, and we have learned that in fact they do contribute to transmission.

And finally, of those of us that get symptomatic, it appears that we're shedding significant virus in our oropharyngeal compartment, probably up to 48 hours before we show symptoms. This helps explain how rapidly this virus continues to spread across the country, because we have asymptomatic transmitters and we have individuals who are transmitting 48 hours before they become symptomatic.

Pediatrician says 80% of kids likely have coronavirus, but they're so asymptomatic you'd never know

https://www.cbsnews.com/news/coronavirus-children-pediatrician-80-percent-asymptomatic/

Children are asymptomatic, mildly symptomatic, or note tested. But they are spreading the virus.

Today we will discuss how various phases of a pandemic are used to manage/contain the illness. We will discuss how South Korea and China performed in these phases.

We will then discuss the patient monitoring protocol adapted by Jiangsu Province in China with great patient outcomes.

We will discuss the indications or contraindications of the following drugs:

• Corticosteroids
• Remdesivir
• Hydroxychloroquine
• Azithromycin

Pregnant Women

We will discuss the CDC guidelines for a pregnant woman.

Diabetics and Hypertensive Patients

We will also discuss the possible additional risk to the patients of diabetes mellitus and hypertension that are taking angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs)

References

Some good news

https://www.latimes.com/science/story/2020-03-22/coronavirus-outbreak-nobel-laureate

Persistence of the virus on inanimate surfaces

https://www.sciencedirect.com/science/article/pii/S0195670120300463?via%3Dihub

Lopinavir and Ritonavir did not have any benefit

https://www.nejm.org/doi/full/10.1056/NEJMoa2001282

Treatment of ARDS from COVID-19

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30127-2/fulltext

Use of the masks

https://www.hackensackmeridianhealth.org/HealthU/2020/03/06/answered-4-questions-about-flu-masks/

CDC links to this study (Remdesivir and Chloroquine)

https://www.nature.com/articles/s41422-020-0282-0

Remdesivir

MERS-COV peaks in humans between 7-10 days after the onset of symptoms. This gives a good chance to use Remdesivir.

Early therapy with Remdesivir will help reduce the virus load and the damage due to the immune response.

https://www.nature.com/articles/s41467-019-13940-6

https://www.ncbi.nlm.nih.gov/pubmed/28659436

Hydroxychloroquine and azithromycin

Significant viral load reduction/disappearance

Azithromycin seems to reinforce the effect of hydroxychloroquine

https://www.sciencedirect.com/science/article/pii/S0924857920300996

CDC’s recommendation/opinion for the drug therapy

https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html

https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

How South Korea managed to keep the death rate at 0.6%

Young population

Extensive testing, contact tracing, and quarantining

https://www.wired.co.uk/article/south-korea-coronavirus

South Korea used transactions, phones, and CCTV data to track the patients and their contacts

http://theconversation.com/coronavirus-south-koreas-success-in-controlling-disease-is-due-to-its-acceptance-of-surveillance-134068

https://www.sciencemag.org/news/2020/03/coronavirus-cases-have-dropped-sharply-south-korea-whats-secret-its-success

https://www.nature.com/articles/d41586-020-00740-y

Chloroquine and the NH4Cl

https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-2-69

Lower mortality by early recognition Jiangsu Province China

https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00650-2

Keeping healthcare workers healthy

https://www.newyorker.com/news/news-desk/keeping-the-coronavirus-from-infecting-health-care-workers

Stability of the virus and its sensitivity to heat and irradiation

https://pubmed.ncbi.nlm.nih.gov/14631830/

Patients with diabetes and hypertension

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext?fbclid=IwAR1SkOX-rbnx-ThhEyZ3sVQsD7MjPUxmXKkiMHrciYH-8bFjC7dNi7LH-FM

Pregnant women and COVID-19

https://www.cdc.gov/coronavirus/2019-ncov/prepare/pregnancy-breastfeeding.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fspecific-groups%2Fpregnancy-faq.html

Use of corticosteroids may be harmful

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30317-2/fulltext

Phases

Containment delay mitigation

https://www.rte.ie/news/coronavirus/2020/0312/1121884-covid-19-terms-delay-phase/

In this video Dr. Mobeen discusses:

• The types of Coronaviruses.
• The difference of SARS-COV-2 from the Influenza Viruses.
• The Properties of the SARS-COV-2
• Signs and symptoms of COVID-19
• Diagnosis
• Management approach 
• Preventive measures

Vitamin C

Found in plants, citrus fruits, tomatoes, and green vegetables

Water soluble hence extra dose is peed out.

Deficiency causes scurvy

Large doses cause diarrhea

Reason that people looked into it was that the people with vitamin C deficiency had more occurrences of pneumonia.

Normal dose is 90 mg/day. Add 30 mg/day for pregnant women, and 35 mg/day for smokers.

Functions:

Antioxidant

Neutralize reactive oxygen species or free radicals.

Needed in procollagen hydroxylation during the collagen synthesis.

COVID-19 related

It helps shorten the flu duration by about 8% in adults and 14% in children

Helped prevent the occurrence of flu in people with rigorous physical activity when given in megadoses IV.

It has helped reduce the seriousness and ventilation need by patients.

A study is on going in China that will conclude in September.

Is useful in megadose 

https://www.ncbi.nlm.nih.gov/pubmed/10543583

Claims that megadoses caused 85% reduction in reporting of the flu and cold symptoms.

Mixed results

https://www.healthline.com/nutrition/vitamin-c-coronavirus

Protective for the skin (collagen synthesis.)

Needed by the phagocytic cells when they are performing oxidative burst. NADPH is used to produce reactive oxygen species.

Some evidence that it reduces lung inflammation during the flu infection.

Study in Chinese language

https://mp.weixin.qq.com/s/bF2YhJKiOfe1yimBc4XwOA

Need to study the effects 

https://clinicaltrials.gov/ct2/show/NCT04264533

Study that vitamin c is marginally useful in people engaged in rigorous activities. 

https://www.ncbi.nlm.nih.gov/pubmed/23440782

Marginally helpful. 

https://www.ncbi.nlm.nih.gov/pubmed/28353648

Maybe helpful

https://www.ncbi.nlm.nih.gov/pubmed/29099763

Helpful for the immune cells

https://www.ncbi.nlm.nih.gov/pubmed/16373990

Helpful during infections

https://www.tandfonline.com/doi/full/10.1080/14787210.2020.1706483

Many of our students and friends have been asking about the similarities and the differences of the Novel Coronavirus (SARS-COV-2) disease (COVID-19) and flu which is caused by influenza virus.

Here is a quick video to answer the questions above. 

We will discuss the following topics:

1. Where did the SARS-COV-2 come from?

2. What is a Coronavirus?

3. Who are asymptomatic patients that are unknowingly spreading the disease?

4. What is the incubation period of SARS-COV-2?

5. What outbreaks has it caused in the past?

6. What are the signs and symptoms of the COVID-19?

7. Can we tell if it is COVID-19 or seasonal flu?

8. How to manage the patients of mild, severe, and critical stages of the virus?

9. How does the warm climate help?

10. What are the medicines that are used (unapproved from WHO)?

11. What population segments are most at risk?

12. Questions and answers from the audience.

Chloroquine and hydroxychloroquine are 4-aminoquinoline derivatives. These drugs are weak bases. They make our cell’s cytoplasm and intro-organelle environment basic. This basic environment can hinder virus internalization and assembly in the organelle.

In a study it is also researched that Zinc can also stall viral replication by disabling RNA dependent RNA replicase. However, our cells do not have gates for Zinc to enter into them. The researchers found that these two drugs can act as gates for zinc to enter into the cells. 

Disclaimer: these are possible observations and evolving literature so far. There are no formal studies to prove the first two mechanisms. This might not be true when then studies are done.

https://www.nature.com/articles/s41584-020-0372-x

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456285/

I have seen a lots of incorrect posts about SARS-COV-2. However, one of them is specially dangerous. I go over the false information in that post point by point and discuss the scientific take for why these points are incorrect. Stay safe guys. COVID-19 is serious. Especially for the older ages. Protect them by keeping yourself clean.

Vaccines and Variants (Neutralizing Antibodies vs., Binding Antibodies)

Continuing with our discussions of the vaccines and variants, today I will like to discuss what will happen to neutralized pathogens after the antibodies have neutralized them. Or, if the neutralization failed and they have become binding antibodies only.

What is sterilizing immunity?
https://thehill.com/changing-america/well-being/prevention-cures/501677-what-is-sterilizing-immunity-and-do-we-need-it
https://pubmed.ncbi.nlm.nih.gov/15297622/
https://www.pnas.org/content/101/33/12260
https://www.frontiersin.org/articles/10.3389/fimmu.2020.01166/full
https://www.uab.edu/news/research/item/12027-intranasal-covid-19-vaccine-candidate-shows-sterilizing-immunity-in-preclinical-tests
https://en.wikipedia.org/wiki/Neutralizing_antibody

New Ivermectin Study By Prof. Eli Schwartz (Awesome Results) - Israeli Study

A new study by Prof. Dr. Eli Schwartz et. al. from Israel has shown favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients.

Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19 – A double-blind, randomized placebo-controlled trial
https://www.medrxiv.org/content/10.1101/2021.05.31.21258081v1
Prof. Eli Schwartz
https://eng.sheba.co.il/prof_eli_schwartz

SARS-COV-2 Natural Infections Protects Against Reinfection With 95% Efficacy

A large study in Qatar reveals that the reinfection incidence rate in people who have been infected and recovered from the natural COVID infection is robust for at least 7 months. 95% efficacy is observed. And, the protection does not wane. Instead it increase. Let’s review this study.

Study
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00141-3/fulltext
https://www.thelancet.com/action/showPdf?pii=S2589-5370%2821%2900141-3

Lifelong Protection After COVID Infection (Study)

A peer-reviewed and accepted study shows that we develop long-lived bone marrow resident plasma blasts in quiescent state to provide a potentially lifelong cover against SARS-COV-2. Let’s discuss this fascinating work.

Study and article
https://www.nature.com/articles/d41586-021-01442-9
https://www.nature.com/articles/s41586-021-03647-4
PDF for the study
https://www.nature.com/articles/s41586-021-03647-4_reference.pdf

Reference: The Role of Long-Lived Plasma Cells in Antibody-Mediated Rejection of Kidney Transplantation: An Update - FullText - Kidney Diseases 2019, Vol. 5, No. 4 - Karger Publishers

Soluble Spike Proteins by Adenovirus Vaccines?

A pre-print study has caused a lot of sensation for two reasons. One, that it proves how Adenovirus based vaccines especially AstraZeneca causes clotting. And, second that it shows how the spike proteins are found in the blood. Let’s review this study.

Pre-print
https://www.researchsquare.com/article/rs-558954/v1

PDF of the hypothesis/pre-print
https://assets.researchsquare.com/files/rs-558954/v1/8c30a186-e9e2-47c1-a76c-dc3bdf10c22a.pdf

What has to happen to prove this hypothesis?
1. Incorrect gene splicing has to occur. If not then the rest is not going to work.
2. Spike protein has to be built, but not have the anchoring part.
3. Spike protein has to be soluble, or part of it has to become soluble.
4. It has to be secreted but not able to attach on the surface of the cell.
5. Vaccine has to fail in producing neutralizing antibodies. (Mobeen, spike protein antibodies of any sort that can bind with this free and soluble spike protein.)
6. It has to enter the blood stream safely. Without getting phagocytosed. And, move through the capillary gap junctions.
7. It has to end up in the blood stream, and then combine with ACE2 as well. However, it has to not combine with the ACE2 in the local tissue where these were actually released.
8. Now this combination should be attacked by the antibodies resulting in the local inflammation. But, did we not say that these proteins got out and floated about because there was no antibody to bind to them? So, why there are antibodies binding now when the protein is in the blood?
9. Now, also, the NK cells will attack this complex causing local inflammation. They also need antibodies to be bound to this soluble protein.
10. Complement will also become activated by the Fc receptors. Attracting C3b or activating the complement cascade.

Reference: 
https://en.wikipedia.org/wiki/Antibody-dependent_cellular_cytotoxicity
Profiles of current COVID-19 vaccines | SpringerLink
https://en.wikipedia.org/wiki/N-terminus
https://www.janssen.com/
https://www.janssencovid19vaccine.com/hcp/how-its-designed.html#
https://www.modernatx.com/moderna-blog/shedding-light-our-prophylactic-vaccines-moa
https://www.sciencedirect.com/science/article/pii/S0169409X2100003X
https://en.wikipedia.org/wiki/Antibody-dependent_cellular_cytotoxicity
https://en.wikipedia.org/wiki/N-terminus
https://en.wikipedia.org/wiki/RNA_splicing

Do Vaccinated Individuals Shed Spike Proteins?

Let’s talk about the fate of spike proteins in a person who is vaccinated and is producing spike proteins as a result of the vaccine.

Innate Immune System Reprogramming By Pfizer-BioNTech Vaccine Against SARS-COV-2?

Study
https://www.medrxiv.org/content/10.1101/2021.05.03.21256520v1

Study preprint PDF
https://www.medrxiv.org/content/10.1101/2021.05.03.21256520v1.full.pdf

Innate immunity does develop short-lived reprogramming when exposed to antigens.
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00799/full

Peripheral blood mononuclear cells (PBMNC)
https://en.wikipedia.org/wiki/Peripheral_blood_mononuclear_cell

Interferon Gamma production
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00847/

TLR4
https://en.wikipedia.org/wiki/TLR4

TLR 7/8
https://en.wikipedia.org/wiki/TLR7

Low Histamine Diets for MCAS and Long COVID Patients

Let’s continue our discussion about the post-COVID syndrome (long haul syndrome.) In the talk today we will discuss foods that we can avoid and the foods that we should add to our routine to help identify histamine related triggers.

References:
https://eatbeautiful.net/low-histamine-low-oxalate-food-list-printable/
https://www.histamineintolerance.org.uk/private/treatment/
https://en.wikipedia.org/wiki/Histidine
https://en.wikipedia.org/wiki/Diamine_oxidase

Ivermectin and COVID Anosmia A Review of Studies

It’s been more than a year since COVID related anosmia is seen, studied, and managed in patients. Anosmia occurs both in the acute disease and in the post-covid long haul syndrome (PCLHS). Let’s review the pathophysiology and the current status of the anosmia.

References
May 11th 2020
Prevalence and Duration of Acute Loss of Smell or Taste in COVID-19 Patients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211515/

June 17th 2020
Anosmia in COVID-19: Mechanisms and Significance
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449368/

June 27th 2020
Into the looking glass: Post-viral syndrome post COVID-19
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320866/

July 24th 2020
Harvard article about the olfactory epithelial infection causing anosmia (instead of the olfactory neurons.) I had presented this study in a video.
https://hms.harvard.edu/news/how-covid-19-causes-loss-smell

July 31st 2020
Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia
https://advances.sciencemag.org/content/6/31/eabc5801

August 15th 2020
Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study.
https://www.alliedacademies.org/articles/effects-of-ivermectinazithromycincholecalciferol-combined-therapy-on-covid19-infected-patients-a-proof-of-concept-study.pdf

Sept 11th 2020
Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488171/

Nov 9th 2020
COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice
https://www.nature.com/articles/s41586-020-2943-z

March 23rd 2021
Smell and taste disorders in COVID-19: From pathogenesis to clinical features and outcomes
https://www.sciencedirect.com/science/article/pii/S0304394021000720?via%3Dihub

April 25th 2021
Pathophysiological relationship between COVID-19 and olfactory dysfunction: A systematic review
https://www.sciencedirect.com/science/article/pii/S1808869421000732

Further reading
Type of anosmia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982703/
Olfactory bulb
https://en.wikipedia.org/wiki/Olfactory_bulb

Early COVID Has Signs For Severe and Long Haul Outcomes

Scientists at the University of Cambridge reviewed blood samples of 207 patients and reported on the immune system response variations for various COVID outcomes. Let’s review these variations.

Study pre-print
https://www.medrxiv.org/content/10.1101/2021.01.11.20248765v2
Article on this study: https://www.cam.ac.uk/research/news/likelihood-of-severe-and-long-covid-may-be-established-very-early-on-following-infection
Leprosy as an example of an incorrect response by the immune system
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004335

Are Vaccines Causing Variants? (Responding to the French Noble Laureate)

A French Nobel laureate has claimed that the vaccines are causing the variant generation. Let’s review the posts and his claims.

Montagnier’s Nobel Prize
https://www.nobelprize.org/prizes/medicine/2008/montagnier/facts/
Motagnier’s anti-vaccine stance
https://www.forbes.com/sites/stevensalzberg/2012/05/27/nobel-laureate-joins-anti-vaccination-crowd-at-autism-one/?sh=1d098ad65c53
Fake post
https://www.deccanherald.com/national/fact-check-whatsapp-hoax-claims-nobel-laureate-said-all-vaccinated-people-will-die-within-2-years-989965.html
Fact checking
https://www.snopes.com/fact-check/luc-montagnier-covid-created-lab/

There are no HIV inserts in SARS-COV-2 articles and studies below.
https://www.statnews.com/2020/02/03/retraction-faulty-coronavirus-paper-good-moment-for-science/
https://www.biorxiv.org/content/10.1101/2020.01.30.927871v1
https://www.biorxiv.org/content/10.1101/2020.01.30.927871v2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033698/

Are there variants for SARS-COV-2? Yes, the beginning.
https://nextstrain.org/ncov/global

DrBeen on Antibody Dependent Enhancement (ADE)
https://www.youtube.com/watch?v=qOLksb6PMoA
ADE Article
https://www.sciencedirect.com/science/article/pii/S1201971220307311
https://www.nature.com/articles/s41564-020-00789-5
https://www.medpagetoday.com/special-reports/exclusives/91648

Dolores Cahill transcript with false narrative.
https://thrivespinecenter.com/professor-dolores-cahill-on-the-cv-vaxx/

Vaccine Adverse Events in the US VAERS System

Let’s review VAERS data for the vaccine associated adverse events as reported by the receivers or their family/friends/physicians.

VAERS
https://wonder.cdc.gov/controller/datarequest/D8;jsessionid=D55822FE3A03BA4E0FF7B5622BA4

CDC presentation about the adverse events
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-02/28-03-01/05-covid-Shimabukuro.pdf

Bloomberg tracker for the vaccination
https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/

Don’t know how good is the fact check, however, here is their link:
https://www.factcheck.org/2021/03/scicheck-viral-posts-misuse-vaers-data-to-make-false-claims-about-covid-19-vaccines/

CDC on the vaccine doses in the USA
https://covid.cdc.gov/covid-data-tracker/#vaccinations

Clotting information
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-04-23/03-COVID-Shimabukuro-508.pdf

Cases of myocarditis
https://www.aappublications.org/news/2021/06/10/covid-vaccine-myocarditis-rates-061021

CDC on myocarditis
https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html

ACIP reschedule their meeting for the myocarditis due to Juneteenth holiday. Seriously?
https://www.cdc.gov/vaccines/acip/index.html

Delta Cases On the Rise - How Are Vaccines Doing? 

From the Gov.UK: New analysis by PHE shows for the first time that 2 doses of COVID-19 vaccines are highly effective against hospitalisation from the Delta (B.1.617.2) variant.

UK new cases doubling fast.
https://www.worldometers.info/coronavirus/country/uk/

Another study shows that only 5% of the infected and hospitalized by delta variant are fully vaccinated.
https://www.thesun.co.uk/news/15243572/five-percent-delta-variant-cases-fully-vaccinated-people/

Vaccines highly effective against hospitalisation from Delta variant
https://www.gov.uk/government/news/vaccines-highly-effective-against-hospitalisation-from-delta-variant

Study
https://khub.net/web/phe-national/public-library/-/document_library/v2WsRK3ZlEig/view/479607266
https://khub.net/web/phe-national/public-library/-/document_library/v2WsRK3ZlEig/view_file/479607329?_com_liferay_document_library_web_portlet_DLPortlet_INSTANCE_v2WsRK3ZlEig_redirect=https%3A%2F%2Fkhub.net%3A443%2Fweb%2Fphe-national%2Fpublic-library%2F-%2Fdocument_library%2Fv2WsRK3ZlEig%2Fview%2F479607266

WHO on variant names
https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

BBC describes study with hospitalizations in vaccinated
https://www.bbc.com/news/health-56933756

Vaccine efficacy in older individuals
https://www.bmj.com/content/373/bmj.n1088

More than 90% cases in the UK are delta variant
https://www.theguardian.com/world/2021/jun/11/delta-variant-is-linked-to-90-of-covid-cases-in-uk

Delta is becoming dominant fast
https://time.com/6073345/delta-variant-covid-19/

Breakthrough After Vaccines and After The Natural Infection

Let’s review the CDC stats for the breakthrough cases after vaccination. Remember, CDC considers and counts only the patients that are hospitalized or died after full vaccination. 

CDC Site
May 2021 onwards
https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html
Jan 1st to April 30th 2021
https://www.cdc.gov/mmwr/volumes/70/wr/mm7021e3.htm

Oregon breakthrough cases after a vaccine are 2%
https://www.oregonlive.com/news/2021/06/98-of-oregons-covid-19-cases-have-been-in-unvaccinated-people-2-are-breakthrough-cases.html

Protection after an infection. Qatar study
A study of the the durability of protection in naturally infected patients.
https://www.medrxiv.org/content/10.1101/2021.04.19.21255739v1.full
A study of the breakthrough cases in the infected and recovered patients.
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00141-3/fulltext

Spike Protein Cytotoxicity?

There’s a lot of discussion about the spike proteins in the blood and their cytotoxicity for the endothelial cells. Let’s look at the spike proteins and the possibility of damage by them.

Viral targets for vaccines against COVID-19
https://www.nature.com/articles/s41577-020-00480-0

SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness
https://www.nature.com/articles/s41586-020-2622-0

Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM
https://advances.sciencemag.org/content/7/1/eabe5575.full

A thermostable, closed SARS-CoV-2 spike protein trimer
A thermostable, closed SARS-CoV-2 spike protein trimer | Nature Structural & Molecular Biology

Moderna Patents
https://www.modernatx.com/patents

Bonus reference:
Long haul protocol:
https://covid19criticalcare.com/covid-19-protocols/i-recover-protocol/

Single letter amino acid names
http://130.88.97.239/bioactivity/aacodefrm.html

Study - Spike Proteins in Plasma of Vaccinated (Nothing After The Second Dose)

A small study on healthcare workers demonstrated the production and detection of S1 part of the spike protein and Spike proteins in the plasma of the individuals vaccinated with Moderna vaccine. Let’s review the study.

Study link
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab465/6279075

SARS-COV-2 Spikes in Ovaries from Pfizer-BioNTech Vaccine?

There has been some uncertainty and nervousness about the possibility of the spike proteins in the ovaries after the biodistribution paper from Japan is obtained and reviewed. Let’s review this document.

Biodistribution document by Pfizer
https://www.docdroid.net/xq0Z8B0/pfizer-report-japanese-government-pdf

TrialSite News
https://trialsitenews.com/did-pfizer-fail-to-perform-industry-standard-animal-testing-prior-to-initiation-of-mrna-clinical-trials/

Israeli Study - no effect on ovaries
https://www.medrxiv.org/content/10.1101/2021.04.09.21255195v1
Article
https://www.news-medical.net/news/20210415/Ovarian-follicular-function-unaffected-by-SARS-CoV-2-infection-or-Pfizer-vaccine-study-finds.aspx

An example of a possible misunderstanding
https://www.whatdotheyknow.com/request/reg_174_for_pfizer_covid_19_mrna

Liver’s role in excreting drugs and foreign substances
https://www.ncbi.nlm.nih.gov/books/NBK551679/
Drug metabolism
https://en.wikipedia.org/wiki/Drug_metabolism

Non Classical Monocytes Causing Long Haul

Let’s talk a little more about the mechanism that Dr. Bruce Patterson’s team has observed about the monocytes.

Video discussing the observation here: https://www.youtube.com/watch?v=JwjJs5ZHKJI&list=RDCMUCrtd2wePvAl6RN_D-9jWVQQ&start_radio=1&ab_channel=DrbeenMedicalLectures

Monocyte sub-classes and their functions
https://www.frontiersin.org/articles/10.3389/fimmu.2018.01726/full

What are monocytes?
https://en.wikipedia.org/wiki/Monocyte

Post COVID Long Haul Syndrome (PCLHS) Management

Let’s discuss the first release of the post COVID long-haul syndrome management.

Long haul protocol
https://covid19criticalcare.com/covid-19-protocols/i-recover-protocol/

TLC Conference on this Saturday
https://www.treatlongcovid.com/

Irregular Periods And Vaccines

There have been reports about the irregular periods after vaccination. In this talk today we will discuss the possible reasons and if it is a possible long-term issue.

Estrogen receptors in immunity and autoimmunity
Estrogen receptors in immunity and autoimmunity - PubMed

Endometrium
https://en.wikipedia.org/wiki/Endometrium

Relationship of menstruation and the inflammation (immune system)
https://www.pcrm.org/good-nutrition/nutrition-information/using-foods-against-menstrual-pain

Progesterone receptor
https://en.wikipedia.org/wiki/Progesterone_receptor

Progesterone and the immune system
https://www.doctorsdata.com/resources/uploads/newsletters/progesterone-influences-vitamin-d-and-the-immune-response.html

Some articles
The immune system and the menstrual cycle
https://www.fox32chicago.com/news/some-people-reporting-abnormal-periods-after-receiving-covid-19-vaccine
https://www.nebraskamed.com/COVID/the-covid-19-vaccines-irregular-periods-and-spike-protein-shedding
https://www.medicalnewstoday.com/articles/long-covid-and-periods-the-unspoken-impact-on-female-well-being
https://www.medicalnewstoday.com/articles/325314

Vaccine Caused Clotting - Study Finds The Mechanism

A study printed on 7th July 2021 describes the groundbreaking discovery of the cause of clotting by vaccines. In summary, as we have been discussing in the past. Clotting is caused by the antibodies produced against platelet factor 4. Just as in heparin induced thrombocytopenia (HIT). Let’s review.

Study
https://www.nature.com/articles/s41586-021-03744-4
Study PDF
https://www.nature.com/articles/s41586-021-03744-4_reference.pdf

Platelet factor 4
https://en.wikipedia.org/wiki/Platelet_factor_4
Platelet alpha granules
https://en.wikipedia.org/wiki/Alpha_granule
Heparin
https://en.wikipedia.org/wiki/Heparin
Heparin induced thrombocytopenia
https://en.wikipedia.org/wiki/Heparin-induced_thrombocytopenia
Single letter amino acid codes (PDF)
http://home.sandiego.edu/~cloer/bio490/hare2004_images/AminoAcids_info.pdf

COVID-19 Causes Long-Term Blood Cell Changes

Researchers have proved that COVID-19 causes changes to the blood cell structures. These changes can last for several months in some cases. Let’s review.

Physical phenotype of blood cells is altered in COVID-19
https://www.sciencedirect.com/science/article/pii/S0006349521004549?via%3Dihub

Long-term changes to blood cells triggered by Covid-19 infection
https://www.fau.eu/2021/06/21/news/research/long-term-changes-to-blood-cells-triggered-by-covid-19-infection/

Hypoxia and hypoxemia: https://en.wikipedia.org/wiki/Hypoxemia
RBCs: https://en.wikipedia.org/wiki/Red_blood_cell

Is Intravenous Vaccine Causing Clotting?

A study in mice and lab shows that the platelet aggregation can occur when splenic monocytes attack the activated platelets after an intravenous injection of the ChAdOx1 vaccine. Let’s review this study.

Thrombocytopenia and splenic platelet directed immune responses after intravenous ChAdOx1 nCov-19 administration
https://www.biorxiv.org/content/10.1101/2021.06.29.450356v1

PDF to the pre-print
https://www.biorxiv.org/content/10.1101/2021.06.29.450356v1.full.pdf

Massachusets general hospital cites another study with a different mechanism:
https://advances.massgeneral.org/pulmonary/article.aspx?id=1414
https://www.researchsquare.com/article/rs-440461/v1
https://www.ema.europa.eu/en/documents/product-information/vaxzevria-previously-covid-19-vaccine-astrazeneca-epar-product-information_en.pdf
https://wwwnc.cdc.gov/eid/article/18/3/11-1238_article
https://ashpublications.org/blood/article/109/7/2832/125650/Adenovirus-induced-thrombocytopenia-the-role-of
https://en.wikipedia.org/wiki/Spleen
https://www.ncbi.nlm.nih.gov/books/NBK537307/

99.995% Children Survive COVID - UK Data Shows

This pre-print study finds that the death rate in children and young in UK is 2/million even when including the children with comorbidities. Let’s review this important data.

Study preprint
https://www.researchsquare.com/article/rs-689684/v1
Study PDF
https://assets.researchsquare.com/files/rs-689684/v1/3e4e93fb-4e98-4081-9315-16143c2bbd2b.pdf?c=1625678600
BBC article about the study
https://www.bbc.com/news/health-57766717
BBC on overall cases and deaths in the UK
https://www.bbc.com/news/uk-51768274

UK total deaths (chronological)
https://www.statista.com/statistics/1109595/coronavirus-mortality-in-the-uk/
UK total cases (chronological)
https://www.worldometers.info/coronavirus/country/uk/

How Ivermectin Helps with Epstein Barr Virus (EBV)

Ivermectin potentially helps against the infectious mononucleosis (mono) caused by EBV. Let’s review the mechanism.

An aberrant STAT pathway is central to COVID-19
https://www.nature.com/articles/s41418-020-00633-7

Quantitative proteomics reveals a broad‐spectrum antiviral property of ivermectin, benefiting for COVID‐19 treatment
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536980/

Epstein Barr Virus Reactivation in COVID

A study from China published in May 2021 concluded: We find a high incidence of EBV coinfection in COVID-19 patients. EBV/SARS-CoV-2 coinfection was associated with fever and increased inflammation. EBV reactivation may be associated with the severity of COVID-19. The reactivation of EBV may also be the cause of the COVID long haul symptoms. Let's review.

About infectious Mononucleosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670567/

Study published in nature on May 21st 2021
https://www.nature.com/articles/s41598-021-90351-y

Evidence of Epstein Barr Virus Reactivation in Long COVID Patients

A study published on June 17th 2021 shows that the COVID 30% of the long-haul patients have EBV reactivation. Let's review the study and the evidence presented.

Reference to the study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233978/

Other studies supporting the evidence of EBV in COVID long-haul:
https://pubmed.ncbi.nlm.nih.gov/28956548/
https://pubmed.ncbi.nlm.nih.gov/2987786/
https://pubmed.ncbi.nlm.nih.gov/231279/https://pubmed.ncbi.nlm.nih.gov/33359064/

Researchers Show How SARS-COV-2 Spike Protein Causes Acute Lung Injury in Mice

First study in mice demonstrates that S1 part of the spike protein in combination with hACE2 enzyme triggers cytokine like storm and acute lung injury. Let's review this study.

Study: https://journals.physiology.org/doi/full/10.1152/ajplung.00223.2021
Study PDF: https://journals.physiology.org/doi/pdf/10.1152/ajplung.00223.2021

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

All About The Mu Variant

Mu variant has been declared variant of interest (VOI) by the WHO on August 31st 2021. They have observed immune escaping mutations in its spike protein. Let's review the mu variant.

References:
WHO and other articles about Mu variant:
https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/
https://www.axios.com/delta-mu-variants-covid-133e771f-9b83-4034-bef5-a5d5f4fb8dcc.html
https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---31-august-2021

Tracking the variants:
https://nextstrain.org/ncov/gisaid/global
https://onlinelibrary.wiley.com/doi/10.1002/jmv.27247
https://en.wikipedia.org/wiki/SARS-CoV-2_Mu_variant
https://en.wikipedia.org/wiki/SARS-CoV-2_Delta_variant
https://covariants.org/variants/21H.Mu
https://covariants.org/per-variant

CDC on variant of interest (does not include Mu in the list to date.)
https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html#Interest

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

Delta Variant And Deaths In 50+ Individuals

Today we will focus on the impact of delta variant on the individuals aged 50 and over. We will take the data from the UK’s technical report about the variants. (See math at the end of this description.)

UK vaccination status
https://ourworldindata.org/covid-vaccinations?country=GBR

https://www.worldometers.info/coronavirus/country/uk/

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/997418/Variants_of_Concern_VOC_Technical_Briefing_17.pdf

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/996699/25_June_2021_Risk_assessment_for_SARS-CoV-2_variant_DELTA.pdf

Low vaccination rates in ethnic minorities
https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/healthinequalities/bulletins/coronavirusandvaccinationratesinpeopleaged70yearsandoverbysociodemographiccharacteristicengland/8december2020to12april2021

UK ethnicity and age data
https://www.ethnicity-facts-figures.service.gov.uk/uk-population-by-ethnicity/demographics/age-groups/latest

Articles
Revealed: Just 26 fully vaccinated people have died with Indian COVID variant
https://news.yahoo.com/revealed-fully-vaccinated-died-delta-indian-variant-coronavirus-102623618.html

Why The Delta Variant Matters If You’re Vaccinated Or Unvaccinated
https://gothamist.com/news/why-the-delta-variant-matters-if-youre-vaccinated-or-unvaccinated

Nearly all COVID deaths in US now among unvaccinated; Sydney tightens pandemic restrictions amid outbreak: Latest COVID-19 updates
https://www.usatoday.com/story/news/health/2021/06/24/covid-vaccine-delta-variant-california-fda-cdc-missouri-hotspot/5329714001/

Israel says the Delta variant is infecting vaccinated people, representing as many as 50% of new cases. But they're less severe.
https://www.businessinsider.com/israel-50-of-delta-variant-cases-vaccinated-severe-2021-6

https://www.usatoday.com/story/news/health/2021/06/24/covid-vaccine-delta-variant-california-fda-cdc-missouri-hotspot/5329714001/

Data
Delta 50+ 
Cases since Feb 1 
Cases in the cohort that received 2 doses: 3,546
Deaths: 50 (0.06%)

Unvaccinated: 976
Deaths: 38 (3.9%)

Consider that received second dose can still be a risky time.
Absolute risk reduction: 3.9-0.06 = 3.84%
Relative Risk = Risk in vaccinated/risk in placebo = 0.06/3.9 = 0.015
Efficacy: 1 - Relative Risk = 1 - 0.015 = 0.985 = 98%

Cases in the cohort that received 1 dose: 3,953
Deaths: 18 (0.45%)

Unvaccinated: 976
Deaths: 38 (3.9%)

Consider that received second dose can still be a risky time.
Absolute risk reduction: 3.9-0.45 = 3.45%
Relative Risk = Risk in vaccinated/risk in placebo = 0.45/3.9 = 0.12
Efficacy: 1 - Relative Risk = 1 - 0.12 = 0.88 = 88%

This is 2011 data (2021 is not available to me yet.)
Vaccination breakdown in 50+ individuals in UK
UK population: ~58 Millions in 2011
34% (19,385,844) were 50+ 
White British Individuals: 18,164,882 (93.7%)
All others: 1,220,962

Extrapolation for the 10 Million
50+ (34%) = 340,000
Whites (93% of 340,000) = 316,200
All the rest: 23,800

Extrapolated 50+ data in 2021
Total 50+ population = 19,725,844
White (93%): 18,345,034
Rest (7%) = 1,380,810

Vaccination rates in 50+
Whites: 93.7% = 17,244,331
Others: 75% = 1,035,607

Total 50+ vaccinated = 18,279,938 total deaths: cases: 9,571 deaths: 68 (0.71%)
Total 50+ vaccinated = 18,279,938 total deaths (after second dose): cases: 3,546 deaths: 50 (1.5%)
Total 50+ unvaccinated: 1,445,906 total deaths: cases: 976 deaths 38 (3.89%)

Delta Variant UK Analysis

Let’s review SARS-COV-2 DETLA Variant and it’s impact in the UK. 

UK vaccination status
https://ourworldindata.org/covid-vaccinations?country=GBR

https://www.worldometers.info/coronavirus/country/uk/

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/997418/Variants_of_Concern_VOC_Technical_Briefing_17.pdf

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/996699/25_June_2021_Risk_assessment_for_SARS-CoV-2_variant_DELTA.pdf

Low vaccination rates in ethnic minorities
https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/healthinequalities/bulletins/coronavirusandvaccinationratesinpeopleaged70yearsandoverbysociodemographiccharacteristicengland/8december2020to12april2021

UK ethnicity and age data
https://www.ethnicity-facts-figures.service.gov.uk/uk-population-by-ethnicity/demographics/age-groups/latest

Articles
Revealed: Just 26 fully vaccinated people have died with Indian COVID variant
https://news.yahoo.com/revealed-fully-vaccinated-died-delta-indian-variant-coronavirus-102623618.html

Why The Delta Variant Matters If You’re Vaccinated Or Unvaccinated
https://gothamist.com/news/why-the-delta-variant-matters-if-youre-vaccinated-or-unvaccinated

Nearly all COVID deaths in US now among unvaccinated; Sydney tightens pandemic restrictions amid outbreak: Latest COVID-19 updates
https://www.usatoday.com/story/news/health/2021/06/24/covid-vaccine-delta-variant-california-fda-cdc-missouri-hotspot/5329714001/

Israel says the Delta variant is infecting vaccinated people, representing as many as 50% of new cases. But they're less severe.
https://www.businessinsider.com/israel-50-of-delta-variant-cases-vaccinated-severe-2021-6

https://www.usatoday.com/story/news/health/2021/06/24/covid-vaccine-delta-variant-california-fda-cdc-missouri-hotspot/5329714001/