Most prevalent Cov19 co-morbs:
6)Chronic respiratory disease (esp COPD)
These are diverse diseases & increasing age technically not a disease at all. However, there is at least 1 factor in common among all of the co-morbidities identified thus far:
A survey of the co-morbidities revealed another commonality; a close association w/ dysregulation of the pro-inflammatory, neutrophil-recruiting cytokine, IL-17A.
IL-17A is made by multiple immune cell types, including lung-resident innate lymphoid cells (ILC3s).
Impossible to decouple from hypertension - see /6
IL-17A producing cells are closely associated w/cancer. Depending on cancer type, IL-17A may have pro or anti-tumorigenic effects.
Chronic inflammation contributes to cancer development, growth, therapy resistance & metastasis (31315034)
see 2-11. Obesity/metabolic syndrome increases chances of all of these conditions.
How might chronic inflammation (& elevated IL-17A) contribute to #covid19 1) susceptibility and/or 2) severity?
IL-17A inhibits IFN-λ , the first line of defense against respiratory viruses!
"•IFNλs are the 1st IFNs produced that suppress initial viral spread
•IFNλs exhibit potent antiviral functions w/o activating inflammation
•Type I IFNs come up later to enhance antiviral & pro-inflammatory responses"
This leads to 1st hypothesis:
Individuals w/inflammation that affects the airways (including the vasculature) are less able to activate an effective first line defense against CoV-2. This would mean that more virus can get past upper airway & into alveolar spaces of lungs.
IFN-λ allows neutrophils 2 respond w/o promoting inflammation (24952503) BUT IFN-λ requires IRF3 for expression ncbi.nlm.nih.gov/pmc/articles/P…
SARS ORF1ab inhibits IRF3 activity (PMID25481026/19369340/others)
CoV19 also has ORF1ab & likely does same =
major neutrophilic response