key: cord-0700669-o4ckxc3u
authors: Alberca, Gabriela Gama Freire; Alberca, Ricardo Wesley
title: Role of vitamin D deficiency and comorbidities in COVID-19
date: 2022-01-25
journal: World J Virol
DOI: 10.5501/wjv.v11.i1.85
sha: c69e8e2a8d651c414176d7dbf381bf3e1bac5375
doc_id: 700669
cord_uid: o4ckxc3u

Recent manuscripts described the incidence of vitamin D hypovitaminosis in coronavirus disease 2019 (COVID-19) patients. Vitamin D deficiency is also common in patients with comorbidities that are associated with a poor COVID-19 prognosis. In this letter, we review the literature regarding the association of comorbidities, vitamin D deficiency, and COVID-19.

We read with great interest the article entitled "Association between population vitamin D status and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related serious-critical illness and deaths: An ecological integrative approach" recently published by Papadimitriou et al [1] in the World Journal of Virology [1] . This manuscript raised important questions and the authors performed an extensive analysis on vitamin D levels and COVID-19 incidence and severity in Europe, and the potential benefits of vitamin D supplementation to enhance the immune response to the SARS-CoV-2[1]. In the light of these results, we humbly want to state a few points for consideration.

Severe Vitamin D deficiency is associated with poor response to respiratory infections[10], and few reports have identified vitamin D deficiency in moderate and severe COVID-19 patients with conflicting results [1, 11, 12] .

Vitamin D receptor is expressed in many immune cells, including monocytes, macrophages, dendritic cells, neutrophils, and lymphocytes [13] [14] [15] . Vitamin D increases the antimicrobial activity of monocytes and macrophages [16] and has antiinflammatory effects due to the induction of T regulatory cells and reduction in the T helper-17 immune response and pro-inflammatory cytokine production [15] .

Papadimitriou et al [1] performed an important investigation on the association of vitamin D deficiency and COVID-19[1]. Vitamin D levels can be influenced by many factors such as sun exposure, genetics, supplementation, and comorbidities [17] [18] [19] [20] .

Vitamin D hypovitaminosis is associated with several comorbidities that are also related to poor COVID-19 prognoses such as old age [21 Besides comorbidities, vitamin D hypovitaminosis is associated with poor glycemic control [23] , which is also associated with poor COVID-19 outcomes in diabetic and non-diabetic patients [31] . Cancer patients present low circulating levels of vitamin D [29] and experimental models have identified that vitamin D can modulate the disease development by regulating cell cycle and inflammatory response [32] .

Vitamin D deficiency is a worldwide problem [33, 34] , and vitamin D supplementation has the potential to enhance the immune response to microorganisms[1]. Vitamin D supplementation has been investigated for the treatment and prevention of severe COVID-19, indicating a potential reduction in COVID-19 severity [35] .

A recent investigation found that prophylactic vitamin D supplementation in elderlies improved the SARS-CoV-2 immune response [36] , and another investigation identified that the treatment with vitamin D reduces COVID-19 severity [37] . Nevertheless, another report found no additional benefit in vitamin D supplementation during .

Low vitamin D levels also modulate the Renin-Angiotensin-System, which could increase the susceptibility to , since SARS-CoV-2 uses the angiotensinconverting enzyme 2 and Transmembrane Protease Serine 2 (TMPRSS2) to invade the host's cells [40] . In addition, the lack of vitamin D is a risk factor for the development of autoimmune and neuropsychiatric disorders [41] . Lakkireddy et al[42] identified that increasing the serum levels of vitamin D to 80-100 ng/mL significantly reduced inflammatory biomarkers such as interleukin-6, C-reactive protein, and neutrophil-to-lymphocyte ratio during COVID-19, without side effects [42] .

In addition, Papadimitriou et al [1] recommendation for vitamin D supplementation should also be considered in a broader context[1], outside the COVID-19 pandemic situation, due to the high incidence of vitamin D hypovitaminosis worldwide, the vast associations with other diseases, and the proposed doses do not require medical supervision [1] .

COVID-19 vaccination is ongoing worldwide [43] [44] [45] , since vitamin D can modulate the immune response to vaccines [46, 47] , investigations on the vaccines should consider evaluating vitamin D levels and the effects of supplementation on the immune response to vaccines.

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Vitamin D and Chronic Diseases

Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease

COVID-19 vaccine BNT162b1 elicits human antibody and T H 1 T cell responses

Douoguih M; ENSEMBLE Study Group. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial

Let there be light": the role of vitamin D in the immune response to vaccines