Putative Role of Vitamin D for COVID-19 Vaccination

Abstract

Severe acute respiratory syndrome coronavirus 2 is a new, highly pathogenic virus that has recently elicited a global pandemic called the 2019 coronavirus disease (COVID-19). COVID-19 is characterized by significant immune dysfunction, which is caused by strong but unregulated innate immunity with depressed adaptive immunity. Reduced and delayed responses to interferons (IFN-I/IFN-III) can increase the synthesis of proinflammatory cytokines and extensive immune cell infiltration into the airways, leading to pulmonary disease. The development of effective treatments for severe COVID-19 patients relies on our knowledge of the pathophysiological components of this imbalanced innate immune response. Strategies to address innate response factors will be essential. Significant efforts are currently underway to develop vaccines against SARS-CoV-2. COVID-19 vaccines, such as inactivated DNA, mRNA, and protein subunit vaccines, have already been applied in clinical use. Various vaccines display different levels of effectiveness, and it is important to continue to optimize and update their composition in order to increase their effectiveness. However, due to the continuous emergence of variant viruses, improving the immunity of the general public may also increase the effectiveness of the vaccines. Many observational studies have demonstrated that serum levels of vitamin D are inversely correlated with the incidence or severity of COVID-19. Extensive evidence has shown that vitamin D supplementation could be vital in mitigating the progression of COVID-19 to reduce its severity. Vitamin D defends against SARS-CoV-2 through a complex mechanism through interactions between the modulation of innate and adaptive immune reactions, ACE2 expression, and inhibition of the renin-angiotensin system (RAS). However, it remains unclear whether Vit-D also plays an important role in the effectiveness of different COVID-19 vaccines. Based on analysis of the molecular mechanism involved, we speculated that vit-D, via various immune signaling pathways, plays a complementary role in the development of vaccine efficacy.

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

“…In general, it has been demonstrated that vitamin D induce antimicrobial peptides and mediates anti-inflammatory, antiviral, apoptotic, and autophagic activities [ 6–9 , 17 , 30 ]. 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 ].…”

“…While strong observational evidence [ 11–16 ] indicate the association of low vitamin D levels to the COVID-19 susceptibility, severity, and mortality outcomes, the beneficial use of vitamin D supplements in COVID-19 has been reported in some non-randomized observational cohorts [ 17 , 18 ]. Vitamin D supplementation has also been suggested as a putative useful tool to enhance immune responses to COVID-19 vaccines [ 19 , 20 ]. However, there is still a scarcity of information through randomized controlled trials (RCTs) on the use of vitamin D supplementation in COVID-19 patients.…”

Relationship between Vitamin D Status and Antibody Response to COVID-19 mRNA Vaccination in Healthy Adults

“…The underlying rationale for improving the vitamin D status as a preventive or therapeutic measure in the fight against SARS-CoV-2 is based on the multiple interactions of vitamin D with cells of the innate and adaptive immune system [ 7 , 8 , 9 ]. In addition to the immune system, protective effects of vitamin D are also described on ACE2 expression and the renin-angiotensin system (RAS) [ 10 ]. The experimental findings are supported by a number of successful clinical studies, which overall contribute to the high regard for vitamin D as a promising supplement in prevention and a meaningful adjuvant in the treatment of COVID-19 [ 11 , 12 ].…”

Results From the REsCue Trial: A Randomized Controlled Trial with Extended-Release Calcifediol in Symptomatic Outpatients with COVID-19

“…Vitamin D repletion is purported to reduce the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1,2 , mitigate severity of coronavirus disease 2019 (COVID-19) 3 and accelerate recovery 4 . Sufficient serum total 25-hydroxyvitamin D (25D) is postulated to potentiate COVID-19 vaccine effectiveness 5 , boost innate and control adaptive immunity 6,7 , and reduce post-infection cytokine storm 6 and lung injury 8 . A serum 25D level of approximately 50 ng/mL is proposed as the theoretical threshold for zero mortality from COVID-19 based on regression analysis of decreasing deaths rates with rising serum 25D levels 9 .…”