Letter: Covid-19, and vitamin D. Authors' reply.

EDITORS,

We read with great interest the letter from Drs Panarese and Shahini, regarding our review article. We are glad that our review has helped Italian colleagues in this pandemic and grateful for their comments.

Interestingly, they found that northerly latitude is associated with increased mortality rate and hospitalisation rate for COVID‐19 worldwide. One possible explanation was the vitamin D deficiency due to low ultraviolet exposure in Northern countries and now probably compounded by “shut‐down” measures, as mentioned by Drs Panarese and Shahini. It has also been suggested that weather conditions of low temperature and relative humidity might allow the virus to survive longer outside the body than under warmer conditions.

A recent review that also supported the possibility of vitamin D reducing the risk of COVID‐19 infections and deaths documented the various relevant actions of vitamin D. These include maintenance of cell junctions, strengthening cellular immunity by reducing the cytokine storm with impacts on tumour necrosis factor α and interferon γ, and modulating adaptive immunity through suppressing T helper cell type 1 (Th1) responses and promoting induction of T regulatory cells. Vitamin D supplementation increases the CD4+ T cell count in HIV infection, and one of the main manifestations of severe SARS‐CoV‐2 infection was lymphopenia. Vitamin D deficiency can therefore be implicated in ARDS, and heart failure as well as sepsis, and these can all be manifestations of critically ill COVID‐19 patients.

It is also important that vitamin D is involved in two other critical regulatory systems. Thus hypovitaminosis D promotes the renin‐angiotensin system (RAS), chronic activation of which may lead to chronic cardiovascular disease (CVD) and decreased lung function. Patients with these comorbidities account for a higher proportion of critically ill cases in COVID‐19. Recently Hanff et al speculated that CVD or RAS blockade drugs might augment ACE2 levels, increasing available substrate for SARS‐CoV‐2 infection. SARS‐CoV‐2 infection is thought to downregulate ACE2 function, leading to toxic Angiotensin II overaccumulation which in turn may contribute to ARDS or fulminant myocarditis. Another prominent feature of severe COVID‐19 is coagulopathy. A higher level of D‐dimer was found in ICU patients than non‐ICU patients, indicating a predominantly pro‐thrombotic DIC. It was confirmed in pathology that microvascular thrombosis was found in lung tissues of COVID‐19. Vitamin D deficiency has also been reported to correlate with increased risk for thrombosis, and vitamin D controls the expression of several genes relevant to cellular proliferation, differentiation, apoptosis, and angiogenesis.

Therefore, together with Drs Panarese and Shahini, we agree that vitamin D deficiency may well be associated with an increased risk of severity in COVID‐19. Further study of the impact of vitamin D levels on outcome in hospitalised patients is urgently needed. Meanwhile, it seems highly plausible that appropriate supplementation of vitamin D, as already recommended for populations with high prevalence of vitamin D deficiency, may reduce the risk of severe COVID‐19 outcomes.

The authors' declarations of personal and financial interests are unchanged from those in the original article.