Dr Patterson's with Dr Syed discussion seems to suggest that COVID-19 may cause enough large scale diffuse tissue infiltration, damage and cellular death that requires CD8 cells to clean up while perhaps also spilling intracellular remnant Sars-Cov-2 mRNA into the extracellular space where it is picked up by macrophages and presented thereby continuing to positively feedback on the TH1 system sending it into overdrive (and appearing like a cellular autoimmune process similar to what is seen in other autoimmune conditions where CD8 T cell deficiency is also seen) .
But the damage may be so large that the over all production of CD8 cells is overwhelmed (which may also be age dependent and linked to gut microbial health; see below) and cannot keep up thereby reducing their 'steady state' levels below their normal 30% range.
I suspect this might also be associated with a degree of inflammation so it would be interesting to know what inflammatory marker levels (e.g. CRP , etc) are like during this time.
Restoration of CD8 cell levels and reduction in the number of Sars-Cov-2 mRNA Ag-presenting cells on recovery might support this hypothesis.
On a similar note it is my understanding that naive T cells are primarily generated in the Thymus but after involution (which occurs progressively with aging, see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750859/ ===> do we we then have a finite number of T cells and does this resource get over taxed/depleted with viruses like COVID, I wonder?) may mature in the liver and intestine.
In the latter case T cell maturation appears to be linked to the gut microbiome in a tight homeostatic fashion, see: https://pubmed.ncbi.nlm.nih.gov/31026411/ ).
Gut microbiome is disrupted by environmental factors the most significant one being diet (high animal protein/fat content vs low fat plant based , see https://pubmed.ncbi.nlm.nih.gov/21885731/ )and this can lead to immune dysregulation, see https://www.nature.com/articles/s41422-020-0332-7 ) and a host of intestinal and extra-intestinal inflammatory diseases.
Which brings me to the interesting recent study:
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A link between Microbiome and COVID-Long Haulers?
Nick Arrizza - 2021-01-31 21:59:43
p.s. After all this it is my guess that anything that can be done to reduce viral load and viral replication in the early and middle stages will be crucial to stemming the amount of tissue damage that needs to be addressed later thereby sparing the impact on T cell resources and mitigating the potential of Long Hauler Syndrome. |