Thread by @abledoc

Asians & others with darker skin living in Northern latitudes are prone to Vitamin D Deficiency? Severe COVID19 males had lower vitamin D levels. (Females take more supplements) Vitamin D plays key roles in cardiovascular & immune systems 1/n #VitaminD
blogs.scientificamerican.com/observations/a…

https://twitter.com/abledoc/status/1258394818343915523

Vitamin D regulates the expression of PLC-γ1 in naive T cells & is key to T cell responsiveness in humans. Poor primary T cell response can affect immune responses to viral infections including influenza & coronaviruses. 2/n @Ms_Aflatoon #VitaminD
nature.com/articles/ni.18…

Vitamin D necessary for IFN-γ–induced antimicrobial peptide cathelicidin expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity crucial to TB & leprosy immunity. Before antibiotics sunlight was the only treatment for tuberculosis 3/n
stm.sciencemag.org/content/3/104/…

While kidneys & liver are the main sites of Vitamin D metabolism, lymphocytes can activate their own Vitamin D, hence it is an important immune hormone. Besides activation of immunity, Vitamin is also important in down regulating immune responses. 4/n #VitaminD

Immunoregulatory functions of Vitamin D. Besides helping in immune activation, vitamin D also keeps it in check.
Most inflammatory cytokine promoter regions have Vitamin D response elements. Actual effects are complex however & context dependent.

Vitamin D augments expression of chemokine receptors required for lymphocyte trafficking to mucosal sites, a key step in mucosal immunity. Not surprisingly Vitamin D enhances Immunoglobulin A (IgA) secretion in humans & animals. 5/n #VitaminD #Immunity
ncbi.nlm.nih.gov/pubmed/31099085

Cardiovascular & All-Cause mortality is increased in Vitamin D Deficiency. Is it beyond coincidence that COVID19 mortality shares similar risks namely obesity, hypertension, heart disease. Lower the Vitamin D, greater the risk. #VitaminD 6/n #COVID19
onlinejacc.org/content/accj/5…

Relationship of Cardiovascular Risk & Vitamin D levels follow a saddle shaped curve. Steeper risk at low levels a slow rise (wider uncertainty) at higher levels. (Latter could also be a confounder due to sicker patients getting supranormal prescriptions 7/n #VitaminD @maryashakil

Most of the increased Cardiovascular Risk with Vitamin D Deficiency is associated with Hypertension
Obese hypertension is specifically associated with Vitamin D deficiency Obese hypertensives have increased tissue Plasminogen activator inhibitor 1 increasing thrombotic risk 8/n

Vitamin D lowers vascular expression of tPAI-1, thrombomodulin and thrombospondin-1 all of which increase coagulation risk in heart disease.
The same pathways could be operative in COVID19.
Guess what increases expression of tPAI-1 & Tissue Factor. 9/n #VitaminD