The Relationship Between the Severity and Mortality of SARS-CoV-2 Infection and 25-hydroxyvitamin D Concentration—A Metaanalysis

Abstract

Introduction: There is increasing scientific interest in the possible association between hypovitaminosis D and the risk of SARS-CoV-2 infection severity and/or mortality. Objective: To conduct a metanalysis of the association between 25-hydroxyvitamin D (25(OH)D) concentration and SARS-CoV-2 infection severity or mortality. Material and methods: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for studies published between December 2019 and December 2020. Effect statistics were pooled using random effects models. The quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Targeted outcomes: mortality and severity proportions in COVID-19 patients with 25(OH)D deficiency, defined as serum 25(OH)D < 50 nmol/L. Results: In the 23 studies included (n = 2692), the mean age was 60.8 (SD ± 15.9) years and 53.8% were men. Results suggested that vitamin 25(OH)D deficiency was associated with increased risk of severe SARS-CoV-2 disease (RR 2.00; 95% CI 1.47-2.71, 17 studies) and mortality (RR 2.45; 95% CI 1.24-4.84, 13 studies). Only 7/23 studies reported C-reactive protein values, all of which were > 10 mg/L. Conclusions 25(OH)D deficiency seems associated with increased SARS-CoV-2 infection severity and mortality. However, findings do not imply causality, and randomized controlled trials are required, and new studies should be designed to determine if decreased 25(OH)D is an epiphenomenon or consequence of the inflammatory process associated with severe forms of SARS-CoV-2. Meanwhile, the concentration of 25(OH)D could be considered as a negative acute phase reactant and a poor prognosis in COVID-19 infection.

Shared genomic architecture between COVID-19 severity and numerous clinical and physiologic parameters revealed by LD score regression analysis

“…, ivermectin, hydroxychloroquine, azithromycin, and dexamethasone), vitamin and nutrient supplementation has been widely studied. Global mortality rate differences associated with latitude and clinical observations of low serum 25-hydroxyvitamin D levels among hospitalized COVID-19 patients has perhaps garnered greatest attention 22 , but we did not observe a significant association between genetic determinants of vitamin D levels and COVID-19 severity. However, we observed nominally significant protective effects for less-studied nutrient-related traits, including magnesium, calcium, retinol, and vitamin E. A combined vitamin D/magnesium/vitamin B12 combination was associated with a reduction in the proportion of elderly COVID-19 patients requiring oxygen support and intensive care support in a small prospective cohort 23 , and lower plasma retinol levels have also been observed in hospitalized COVID-19 patients 24 .…”

Circadian rhythm disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19

“…However, this prevalence of Vitamin D deficiency falls within the range of estimates for general populations in industrialized nations ( Bakaloudi and Chourdakis, 2022 ). A meta-analysis of SARS-CoV-2 infections confirmed that Vitamin D deficiency was associated with severe disease ( Oscanoa et al., 2021 ), but prospective studies in 149 PASC patients followed a median of 79 days found no correlation of Vitamin D deficiency with fatigue ( Townsend et al., 2021 ). Therefore, the link between Vitamin D and PASC is not supported by high quality evidence and is overall weak.…”

Investigating the Relationship between Vitamin D and Persistent Symptoms Following SARS-CoV-2 Infection

“…Vitamin D deficiency appears to be associated with severe disease, with some evidence suggesting that vitamin D plays a protective role [ 29 , 30 ]. A recent comprehensive systematic review of 23 studies concluded that while vitamin D deficiency seems to be associated with increased severity and mortality in COVID-19, these findings do not imply causality, and further well-designed prospective studies are required to decipher if deficiency is an epiphenomenon or consequence of the inflammatory response in severe COVID-19 illness [ 31 ]. Of note, a recent large mendelian randomization study did not support an association between vitamin D levels and COVID-19 susceptibility, severity or hospitalization in a large consortium of cases and controls [ 32 ].…”