Introduction To P Values and Power

About This Video

CME Pending

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

Videos in this module - view all

COVID-19 Videos

COVID-19 Primarily A Vascular Disease Watch Now (24:08)

COVID Long Haul Management Protocol Watch Now (24:31)

Mixing Vaccine Types - UK Study Watch Now (12:18)

Increased Breakthrough Rates Of South African Variant From Pfizer-BioNTech Vaccine - An Israeli Study Watch Now (18:30)

Non-Neutralizing Antibodies From mRNA Vaccines Watch Now (34:31)

Delta, Viral Burden Vaccine Effectiveness Against New SARS-CoV-2 Infections In The UK Watch Now (38:53)

COVID-19 and Sickle Cell, Thalassemia, and Hemophilia (Full Session) Watch Now (45:16)

Pfizer Vaccine For Kids 12 Years and Above Granted EUA By FDA Watch Now (08:15)

Children Have Better Immune Systems Watch Now (24:03)

Boosting The Innate Arm of Your Immune System Watch Now (26:22)

Ivermectin, Abbott, Sniffer Dogs and ICAM Protocol Watch Now (23:26)

Must Watch- COVID-19 Management With Dr. Paul Marik - Author Of MATH+ Protocol Watch Now (43:34)

Dosage For Vitamin D, K2, and Calcium Watch Now (29:10)

Icelandic Study - Antibody Immunity Lasts Longer Watch Now (16:47)

Bromhexine Study, SARS-COV-2 Antibody Cocktail Watch Now (19:41)

News, Mini Proteins, UVC 222nm, CDC Watch Now (24:54)

Is a Positive PCR Test Really Positive Watch Now (39:00)

Vaccines Update, NEJM Weighs In Watch Now (24:18)

Bromhexine Protocol By Dr. Harrison Watch Now (32:12)

A Case of Reinfection Watch Now (30:35)

Brain Fog and Other Symptoms In Long Haulers Watch Now (21:29) Questions

Seasonal Specific Antibodies and Severity of COVID-19 Watch Now (23:29)

Dr. Zelenko Discusses COVID-19 Outpatient Management Watch Now (39:47)

Latest Study Early Management with HCQ - Dr. Zelenko Watch Now (13:40)

Ivermectin Works For COVID-19 Watch Now (27:40)

High Dose Thiamine And Cytokine Storm Watch Now (20:16)

FDA Approves Remdesivir for COVID-19 Watch Now (28:06)

Hydroxychloroquine Studies Are Still Confusing Watch Now (22:25)

Ranitidine Bismuth Citrate (RBC) For COVID-19 Watch Now (18:22)

Vaccine Update- BioNTech and Pfizer’s Vaccine Watch Now (19:40)

Ivermectin Reduces Mortality Watch Now (16:14)

Mouth Washes That Inactivate Coronaviruses Watch Now (20:46)

Two Studies About Vitamin C and D Watch Now (24:36)

Declining Prevalence of Antibody Positivity to SARS-CoV-2 Watch Now (19:29)

How SARS-COV-2 Disrupts Our Defense Watch Now (21:40)

Preliminary Predictive Criteria for COVID-19 Cytokine Storm Watch Now (24:55)

Introduction To P Values and Power Currently Watching (26:02) Questions

Cloth Masks Do Not Cause Hypoxia Watch Now (09:05)

Antibody Immunity Lasts And Matures At 6 Months Watch Now (22:45)

AstraZeneca Vaccine is 62% and 90% Effective Watch Now (23:24)

Dr. Paul Marik Discusses His I-MASK+ Protocol Watch Now (42:19)

Honey and Nigella Sativa For COVID-19 Watch Now (17:50)

Moderna VS Pfizer: Which is better Watch Now (21:10)

New Strain from the UK- Should We Worry? Watch Now (45:31)

Minks and Masks (WHO and CDC) Watch Now (18:16)

Regeneron Antibody Cocktail Watch Now (08:53)

Allergic Reactions to Pfizer-BionTech Vaccine in UK Watch Now (24:06)

COVID-19-Pregnant Women and Young Babies Watch Now (16:50)

Ivermectin Alone More Effective Than Ivermectin and Doxycycline Watch Now (17:09)

Latest Update About Vaccines (Dec 28th, 2020) Watch Now (28:06)

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 Watch Now (32:40)

AstraZeneca Vaccine And Our Nucleus Watch Now (28:21)

Will the vaccine continue to make spike proteins Watch Now (29:09)

Severe Reactions By Pfizer-BioNTech Vaccine Watch Now (21:48)

SARS-COV-2 - New Brazilian Strain P.1 Manaus Watch Now (19:55)

Antibody-dependent Enhancement of Coronavirus Watch Now (32:38)

J&J Vaccine - Interim Results For Phase 1 and 2 Watch Now (29:40)

South African SARS-COV-2 Variant Watch Now (23:25)

What Antibody Levels Are Necessary For COVID-19 Protection Watch Now (22:06)

Moderna vs. Pfizer-BioNTech Vaccines - An Initial Comparison Watch Now (13:14)

Vitamin D, Dust and Covid-19 Watch Now (15:42)

Recommendation For Immunization Practices From CDC Watch Now (15:26)

Covaxin, A Vaccine from India Watch Now (30:56)

Sinopharm's COVID-19 Vaccine Watch Now (20:00)

Vaccination Results From Israel Watch Now (20:44)

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/

J&J Vaccine - Pandemic Will Be Over Soon Watch Now (12:32)

Sputnik Vaccine is 91.6% Effective Watch Now (19:30)

Covid-19- Testicular Damage and Infertility Watch Now (42:58)

Interferon Beta - A New Study Watch Now (18:05)

AstraZeneca Vaccine Efficacy Update Watch Now (23:00)

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

Vitamin D Cuts COVID Deaths by 60% Watch Now (26:10)

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 Watch Now (22:08)

COVID Long Hauler Watch Now (24:17)

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 Cell Activation Syndrome (MCAS) Part - 1 Watch Now (27:12)

COVID Long Haulers - Mast Cell Activation Syndrome (MCAS) - Part 2 (Symptoms and Management) Watch Now (31:05)

Will Ivermectin Block a Vaccine? Watch Now (11:57)

Doctors Prescribing Ivermectin (Do Not Publish) Watch Now (05:48)

How is AstraZeneca Vaccine Made Watch Now (07:06)

Ivermectin Still Effective Against The Variants Watch Now (11:31)

Johnson and Johnson Vaccine Efficacy (Approval Data) Watch Now (34:39)

Ivermectin May Help Against Blood Coagulation in COVID Watch Now (22:22)

More Deaths by The UK Variant Watch Now (32:32)

Novavax Phase III and Phase II B Trial Results Watch Now (16:18)

Nasal Spray for Virus/SARS-COV-2 Reduction Watch Now (21:28)

Merck’s Molnupiravir (EIDD-281) Effective Against SARS-COV-2 Watch Now (29:11)

Deaths, Anaphylaxis, And Other Vaccine Adverse Effects (March 16th 2021 - USA) Watch Now (36:44)

Covid 19 Symptoms in Kids Watch Now (19:03)

Vaccine-Induced Clotting- Management Watch Now (21:26)

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) Watch Now (19:04)

Scientists Develop a New Corona Vaccine to Fight All Mutants and Strains of Coronavirus Watch Now (23:01)

Super Vaccine for Coronavirus- More Updates Watch Now (23:06)

Israel Pfizer Vaccine Efficacy At a Large Scale Watch Now (19:53)

Pfizer Vaccine Associated Adverse Effects From Israel Watch Now (55:58)

Risk Of Rare Blood Clotting Higher for COVID- 19 than for Vaccines Watch Now (21:33)

New Technique To Study COVID Pathology (High Parameter Imaging Mass Cytometry) Watch Now (24:49)

Double Mutant Variant in India (B.1.167) Watch Now (18:05)

Administration of Second Dose Of Moderna Vaccine After An Immediate Hypersensitivity Reaction to The First Dose Watch Now (10:46)

Macrolide - Azithromycin Watch Now (24:12) Questions

COVID-19 Vaccines Update (Aug 3rd 2020) Watch Now (22:44)

Vitamin K Deficiency and COVID-19 Watch Now (25:38)

Inhaled Corticosteroids (Budesonide) Watch Now (23:24)

Famotidine (H2 Receptor Antagonist) Watch Now (28:20)

Hydroxychloroquine and Azithromycin Studies Watch Now (21:42)

Norepinephrine Watch Now (32:19)

A Potential Rare Case of Meningitis With COVID-19 Watch Now (17:57)

A Potentially Rare Case of Meningitis with COVID-19 (Labs) Watch Now (33:27)

Vitamin K (Math+ Protocol) Watch Now (15:51)

NAC N-Acetylcysteine Watch Now (27:41) Questions

COVID-19 and Ivermectin, Remdesivir, Leronlimab Watch Now (19:51)

COVID-19 and Selenium (Part of MATH+ Protocol) Watch Now (20:36)

MATH+ Protocol - Latest Updates Watch Now (32:44)

Favipiravir Watch Now (26:05)

Low Dose Radiation for COVID-19 Watch Now (22:05)

Hypercoagulability - Part 2 (Coagulation cascade) Watch Now (41:19)

G6PD Enzyme Deficiency and COVID-19 Watch Now (43:23)

COVID-19 Leronlimab Watch Now (45:46)

MATH+ Protocol For COVID-19 (Part 1) Watch Now (45:24)

Melatonin Watch Now (30:38)

Magnesium Watch Now (35:04)

MATH+ Protocol - ICU Management (Part 3) Watch Now (43:22)

Iodine and Its Medical Uses Watch Now (26:07)

COVID-19 and Epoprostenol (Hypercoagulation Management) Watch Now (20:39)

COVID-19 and Aspirin Watch Now (28:13) Questions

Dexamethasone Watch Now (28:41)

Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) Watch Now (17:47)

MATH+ Protocol - In Hospital Management (Part 2) Watch Now (43:56)

LATEST on Vaccines for COVID-19 Watch Now (29:59)

Thiamine for COVID-19 (HAT Study and MATH+ Protocol) Watch Now (27:29)

Tocilizumab An IL6 Receptor Blocker Watch Now (34:49)

Herd Immunity and Second Wave Watch Now (25:30)

Camostat Mesylate Watch Now (25:14)

COVID-19 Severity and Blood Groups Watch Now (34:25)

COVID-19 Insights: Mutations in SARS-COV-2 Watch Now (29:56)

Is SARS-COV-2 Becoming Weak? Watch Now (36:55)

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 (Co-Enzyme Q) Watch Now (40:11)

Quercetin as Zinc Ionophore & Outpatient Management Watch Now (35:57)

COVID-19 Cases and Test Accuracy Watch Now (31:35)

Oxford and Moderna Vaccines News Part 2 Watch Now (44:54)

Oxford and Moderna Vaccines News Part 1 Watch Now (28:13)

Global View of COVID-19 - (HCQ and Zinc New Studies) Watch Now (34:56)

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

Asthma and COVID-19 Watch Now (42:22)

Vitamin D - Can It Help Fight COVID-19? Watch Now (50:28)

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

Test Image

Convalescent Plasma For COVID-19 Patients Watch Now (50:28)

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

Vaccination Strategies for SARS-COV-2 (COVID-19) Watch Now (47:22)

COVID-19 Insights: Cancer Patients and COVID-19 Watch Now (40:14)

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:

2007 cases from 575 hospitals
Cancer patients have a higher risk of developing COVID-19 compared to other individuals.
Patients with cancer had poorer outcomes compared to non-cancer patients of COVID-19
More patients with SARS-COV-2 get multiorgan organ failure compared to SARS-COV and MERS-COV
Caners patients are at a higher risk of getting infections because of the weak immune system due to the cancers and the cancer treatment.
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.
28% had lung cancers. The highest cancer type with COVID-19.
25% of the cancer and COVID-19 had received chemotherapy or surgery within the last one month.
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.)
25% were cancer survivors.
Cancer patients deteriorated more rapidly than non-cancer COVID-19 patients.

Compared to patients without cancers

Cancer patients were older mean age 63.1 y, vs. 48.7 y.
More likely to have a h/o smoking 22% vs 7%
Had more severe baseline CT manifestations. 94% vs 71%
No difference in sex, other baseline symptoms, or other comorbidities.
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

Higher risk of severe event 75% compared to 43%

Suggestions

If possible postpone elective surgeries and chemotherapy (stable cancer.)
Stronger personal protection measures are needed in the cancer patients.
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:

105 cancer patients with COVID-19 were enrolled. Control group was 536 non-cancer COVID-19 patients
11.43% death rate in patients with cancer compared to 3.8% in patients without cancer.
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

128 hospitalized cancer patients and 226 healthcare workers.
10% of the cancer patients developed COVID-19
7% of the healthcare workers developed COVID-19
Patients with hematological cancers had a CFR of 62% compared to 0 in the healthcare workers that had COVID-19.
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

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

COVID-19 Insights: Monoclonal Antibodies Watch Now (37:39)

Natural Killer Cells Watch Now (33:30)

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 Watch Now (35:08)

Heart Patients And COVID-19 Watch Now (42:04)

COVID-19 (by SARS-COV-2) Healthcare Burden Assessment Watch Now (32:17)

SARS-COV-2 Case Fatality Rate (Death Rates) Watch Now (29:33)

Hypercoagulability Role of the ACE2 Enzyme - Part 1 Watch Now (37:09)

First COVID-19 Case in The USA Watch Now (31:28)

COVID-19 Insights: Hypertension and COVID-19 Watch Now (32:10)

BCG Vaccine Watch Now (37:45)

Lifting the Lockdown Watch Now (37:19)

COVID-19 and Diabetes Watch Now (45:36)

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/

New Study Hydroxychloroquine Watch Now (27:42)

Asymptomatic COVID-19 Patients Watch Now (35:39)

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.

Is Reinfection From SARS-COV-2 Possible? Watch Now (38:30)

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 COVID-19 Slowdown? Watch Now (25:40)

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 Watch Now (40:06)

Does SARS-COV-2 Attack Blood/Hemoglobin? Watch Now (34:09)

Could BCG Vaccine Help Fight COVID-19? Watch Now (44:14)

Asymptomatic Patients of COVID-19 Watch Now (41:08)

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

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.

Management Principles Of COVID-19 (March 20th Update) Watch Now (1:03:04)

SARS-COV-2 (Novel Coronavirus) - An Introduction Watch Now (11:10)

Vitamin C - Can it Help Fight COVID-19? Watch Now (28:46)

Similarities and Differences between COVID-19 (by SARS-COV-2) and the Seasonal Flu Watch Now (07:40)

All About SARS-COV-2 and COVID-19 (March 31st Update) Watch Now (1:54:23)

Can Hydroxychloroquine Work as An Antiviral? Watch Now (28:59)

COVID-19 (by SARS-COV-2) Debunking Myths and Rumors Watch Now (13:23)

Vaccines and Variants (Neutralizing Antibodies vs., Binding Antibodies) Watch Now (34:00)

New Ivermectin Study By Prof. Eli Schwartz Watch Now (24:33)

SARS-COV-2 Natural Infections Protects Against Reinfection With 95% Efficacy Watch Now (17:47)

Lifelong Protection After COVID Infection (Study) Watch Now (32:39)

Soluble Spike Proteins by Vaccines? Watch Now (49:50)

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? Watch Now (49:30)

Innate Immune System Reprogramming By Pfizer-BioNTech Vaccine Against SARS-COV-2? Watch Now (35:07)

Low Histamine Diets Watch Now (19:50)

Ivermectin and COVID Anosmia A Review of Studies Watch Now (17:29)

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 Watch Now (13:48)

Are Vaccines Causing Variants Watch Now (1:14:52)

Vaccine Adverse Events in the US VAERS System Watch Now (36:11)

Vaccines are Highly Effective Against Hospitalization from the Delta Variant Watch Now (19:57)

Breakthrough After Vaccines and After The Natural Infection Watch Now (18:33)

Spike Protein Cytotoxicity Watch Now (19:57)

A Study - Spike Proteins in Plasma of Vaccinated (Nothing After The Second Dose) Watch Now (32:20)

SARS-COV-2 Spikes in Ovaries from Pfizer-BioNTech Vaccine Watch Now (25:09)

Non-Classical Monocytes Causing Long Haul Watch Now (24:55)

Post-COVID Long Haul Syndrome (PCLHS) Management Watch Now (24:52)

Irregular Periods And Vaccines Watch Now (24:05)

Vaccine Caused Clotting - Study Finds The Mechanism Watch Now (29:48)

COVID-19 Causes Long-Term Blood Cell Changes Watch Now (26:24)

Is Intravenous Vaccine Causing Clotting Watch Now (28:14)

99.995% of Children Survive COVID-19 Uk Data Shows Watch Now (25:42)

How Ivermectin Helps with Epstein Barr Virus (EBV) Watch Now (08:29)

Epstein Barr Virus Reactivation in COVID Watch Now (23:28)

Epstein Barr Virus Prevalence in Long COVID Watch Now (19:16)

Researchers Show How SARS-COV-2 Spike Protein Causes Acute Lung Injury in Mice Watch Now (21:14)

All About the Mu Variant Watch Now (23:09)

Delta Variant And Deaths In 50+ Watch Now (09:30)

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 Watch Now (23:47)

Instructor

Dr. Mobeen Syed

Mobeen Syed is the CEO of DrBeen Corp, a modern online medical education marketplace. Mobeen is a medical doctor and a software engineer. He graduated from the prestigious King Edward Medical University Lahore. He has been teaching medicine since 1994. Mobeen is also a software engineer and engineering leader. In this role, Mobeen has run teams consisting of hundreds of engineers and millions of dollars of budgets. Mobeen loves music, teaching, and doing business. He lives in Cupertino CA.

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Instructor

Dr. Mobeen Syed