Thread by @markfmccarty

@Covid19Crusher @jpkiekens @niro60487270 @Ian56789

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.

p38 is typically activated during inflammation, and, via up-regulated activity of AP-1 and NF-kappaB transcription factors, promotes transcription of a wide range of pro-inflammatory cytokines, including many (e.g. IL-6, TNF-alpha) that are key mediators of COVID-19 inflammation.

Figure 1 in that paper is particularly beautiful, as it shows that a deficient concentration of 25OHD - 15 ng/ml - fails to influence cytokine induction by LPS, whereas 30 ng/ml or higher (considered physiologically adequate) does.

I suspect that these findings are pertinent to alveolar macrophages, and to certain bronchial epithelial cells in which 1alpha-hydroxylase is constitutively or inducibly expressed. Hence, good vit D status should be generally useful for dampening excessive lung inflammation.

The new Spanish RCT showing efficacy of high-dose 25OHD in hospitalized COVID-19 patients, states: "adults living in the Córdoba area are relatively vitamin D deficient (16 ng/ml on average) in late winter and early spring".

sciencedirect.com/science/articl…

So the supplementation evidently rapidly increased 25OHD levels to those capable of down-regulating production of pro-inflammatory cytokines.

This effect may be more broadly pertinent to ARDS-inducing lung disorders.

Calcitriol activity can also induce expression of anti-microbial proteins such as cathelicidin which may disrupt enveloped viruses such as SARS-CoV-2. But this effect would likely be most important during the early phases of COVID-19.

Of related interest is a report (from the same team) showing that corticosteroids likewise induce MKP-1, and that calcitriol can amplify their efficacy in this regard:

pubmed.ncbi.nlm.nih.gov/23572530/

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