Here's a paper which may be a Rosetta Stone for understanding the favorable impact of good vit D status in COVID19:
pubmed.ncbi.nlm.nih.gov/22301548/
In human monocytes expressing the 1alpha-hydroxylase activity needed to convert 25OHD to the active hormone calcitriol, physiological levels of 25OHD induce expression of MAPK phosphatase-1 (MPK1), which functions to deactivate p38 MAPK.
SARS-CoV-2 gets into cells either via endosomes, or directly thru the plasma membrane. This requires fusion of the viral lipid membrane with the endosomal or plasma membrane.
But this merger is blocked by the viral spike protein, which protrudes from the viral membrane and is needed for binding to cells via ACE2. This protein must be proteolytically cleaved before membrane fusion can occur.
The key proposition on the table is this: HCQ + AZM +/- Zn, administered just as soon as symptoms arise, greatly reduces need for subsequent hospitalization and risk of death.
I have aggregated all reported large case series I can find evaluating this protocol (including those in Table 1 of Dr. Risch's new letter: pubmed.ncbi.nlm.nih.gov/32685966/) - many focusing on high-risk patients.
SARS-CoV-2 virions attach to the ACE2 membrane protein, then are taken into cells engulfed in endosomes. In order to break into the cytoplasm – where the virus can replicate – the lipid envelope of the virions must fuse with the endosomal membrane.
Cleavage of the viral spike protein by the enzyme cathepsin L is required for this fusion.
The NIH has just shut down its multicenter RCT of HCQ/AZM in early stage COVID-19 outpatients, due to anemic enrollment. After over a month, only 20 subjects had enrolled, whereas the target enrollment was 2,000.
niaid.nih.gov/news-events/bu…
2/A poor effort at patient outreach may have contributed to this outcome, as well as US incompetence with respect to rapid testing of symptomatic subjects. But the likely main factor: Our media and "medical experts" have convinced most Americans that HCQ is toxic and useless.
