Shedding light on vitamin D: the shared mechanistic and pathophysiological role between hypovitaminosis D and COVID-19 risk factors and complications

Abstract

Severe acute respiratory syndrome coronavirus (SARS-COV-2) is the culprit of the Coronavirus Disease (COVID-19), which has infected approximately 173 million people and killed more than 3.73 million. At risk groups including diabetic and obese patients are more vulnerable to COVID-19-related complications and poor outcomes. Substantial evidence points to hypovitaminosis D as a risk factor for severe disease, the need for ICU, and mortality. 1,25(OH)D, a key regulator of calcium homeostasis, is believed to have various immune-regulatory roles including; promoting anti-inflammatory cytokines, down regulating pro-inflammatory cytokines, dampening entry and replication of SARS-COV-2, and the production of antimicrobial peptides. In addition, there are strong connections which suggest that dysregulated 1,25(OH)D levels play a mechanistic and pathophysiologic role in several disease processes that are shared with COVID-19 including: diabetes, obesity, acute respiratory distress syndrome (ARDS), cytokine storm, and even hypercoagulable states. With evidence continuing to grow for the case that low vitamin D status is a risk factor for COVID-19 disease and poor outcomes, there is a need now to address the public health efforts set in place to minimize infection, such as lock down orders, which may have inadvertently increased hypovitaminosis D in the general population and those already at risk (elderly, obese, and disabled). Moreover, there is a need to address the implications of this evidence and how we may apply the use of cheaply available supplementation, which has yet to overcome the near global concern of hypovitaminosis D. In our review, we exhaustively scope these shared pathophysiologic connections between COVID-19 and hypovitaminosis D.

COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials

“…The protective immuno-modulatory effects of this fat-soluble steroid vitamin have been reported in respiratory diseases [ 31 , 32 ] including its role in enhancing immune responses to COVID-19 vaccines [ 19 , 20 ]. Studies have proposed vitamin D deficiency as leading candidate in association with COVID-19 susceptibility, severity, and progression [ 33 , 34 ]. However, there is no strong evidence through RCTs on the therapeutic benefits of vitamin D supplementation in COVID-19 outcomes.…”

COVID-19 and Vitamin D (Co-VIVID Study): a systematic review and meta-analysis of randomized controlled trials

“…The protective immuno-modulatory effects of this fat-soluble steroid vitamin have been reported in respiratory diseases [24,25]. Studies have proposed vitamin D deficiency as leading candidate in association with COVID-19 susceptibility, severity and progression [26,27]. However, there is no strong evidence through RCTs on the therapeutic benefits of vitamin D supplementation in COVID-19 outcomes.…”

High-Dose Vitamin C Supplementation as a Legitimate Anti-SARS-CoV-2 Prophylaxis in Healthy Subjects—Yes or No?

“…Similarly, the need for well-planned follow-up research is shown in the case of vitamin D [ 44 ]. It is believed to have various immune-regulatory roles including: promoting anti-inflammatory or downregulation of proinflammatory cytokines; blocking entry and replication of SARS-CoV-2 or the production of antimicrobial peptides [ 47 ]. There are also indications that lead us to believe that low vitamin D status is a risk factor for COVID-19 disease and poor outcomes, although it is not possible to confirm causality because many risk factors are common to hypovitaminosis D and the severe course of COVID-19.…”

“…There are also indications that lead us to believe that low vitamin D status is a risk factor for COVID-19 disease and poor outcomes, although it is not possible to confirm causality because many risk factors are common to hypovitaminosis D and the severe course of COVID-19. However, although the recommended daily dose that seems to maintain the sufficient serum level of this vitamin, i.e., 400 UI, is known, whether this is enough to gain any benefits for COVID-19 patients or prevention remains unclear [ 42 , 44 , 47 ]. The leading health bodies (Public Health England, the National Institute for Health and Care Excellence and the Scientific Advisory Committee on Nutrition) highlight the need for further research to provide evidence on vitamin D and its beneficial effects on COVID-19, especially high-quality RCTs [ 42 , 44 ].…”