Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes

Abstract

Background: Several studies suggest an association between serum 25-hydroxyvitamin D (25OHD) and the outcomes of Severe Acute Respiratory Syndrome Corona-Virus-2 (SARS-CoV-2) infection, in particular Coronavirus Disease-2019 (COVID-19) related severity and mortality. The aim of the present meta-analysis was to investigate whether vitamin D status is associated with the COVID-19 severity, defined as ARDS requiring admission to intensive care unit (ICU) or mortality (primary endpoints) and with the susceptibility to SARS-CoV-2 and COVID-19-related hospitalization (secondary endpoints). Methods: A search in PubMed, ScienceDirect, Web of Science, Google Scholar, Scopus, and preprints repositories was performed until March 31th 2021 to identify all original observational studies reporting association measures, or enough data to calculate them, between Vitamin D status (insufficiency <75, deficiency <50, or severe deficiency <25 nmol/L) and risk of SARS-CoV-2 infection, COVID-19 hospitalization, ICU admission, or death during COVID-19 hospitalization. Findings: Fifty-four studies (49 as fully-printed and 5 as pre-print publications) were included for a total of 1,403,715 individuals. The association between vitamin D status and SARS-CoV2 infection, COVID-19 related hospitalization, COVID-19 related ICU admission, and COVID-19 related mortality was reported in 17, 9, 27, and 35 studies, respectively. Severe deficiency, deficiency and insufficiency of vitamin D were all associated with ICU admission (odds ratio [OR], 95% confidence intervals [95%CIs]: 2.63, 1.45-4.77; 2.16, 1.43-3.26; 2.83, 1.74-4.61, respectively), mortality (OR, 95%CIs: 2.60, 1.93-3.49; 1.84, 1.26-2.69; 4.15, 1.76-9.77, respectively), SARS-CoV-2 infection (OR, 95%CIs: 1.68, 1.32-2.13; 1.83, 1.43-2.33; 1.49, 1.16-1.91, respectively) and COVID-19 hospitalization (OR, 95%CIs 2.51, 1.63-3.85; 2.38, 1.56-3.63; 1.82, 1.43-2.33). Considering specific subgroups (i.e., Caucasian patients, high quality studies, and studies reporting adjusted association estimates) the results of primary endpoints did not change. Interpretations: Patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 infection and related hospitalization.

Keywords: COVID-19; SARS-CoV-2 infection; intensive care unit; mortality; respiratory distress syndrome; vitamin D.

Figure 1

Flow of study selection process. SARS-CoV-2, Severe Acute Respiratory Syndrome Corona-Virus-2.

Figure 2

The forest-plot reporting the association between COVID-19 related admission to intensive care unit (ICU) and vitamin D thresholds (severe vitamin D deficiency, vitamin D deficiency, and vitamin D insufficiency). COVID-19, Coronavirus Disease-2019; ICU, intensive Care Unit; <25 nmol/L, 25OHD levels below 25 nmol/L; <50 nmol/L, 25OHD levels below 50 nmol/L; <75 nmol/L, 25OHD levels below 75 nmol/L.

Figure 3

The forest-plot reporting the association between COVID-19 related mortality and vitamin D thresholds (severe vitamin D deficiency, vitamin D deficiency, and vitamin D insufficiency). COVID-19, Coronavirus Disease-2019; ICU, intensive Care Unit; <25 nmol/L, 25OHD levels below 25 nmol/L; <50 nmol/L, 25OHD levels below 50 nmol/L; <75 nmol/L, 25OHD levels below 75 nmol/L.

Figure 4

Studies stratified in categories of age, prevalence of males, hypertension and diabetes. COVID-19, Coronavirus Disease-2019; ICU, intensive Care Unit; <25 nmol/L, 25OHD levels below 25 nmol/L; <50 nmol/L, 25OHD levels below 50 nmol/L; <75 nmol/L, 25OHD levels below 75 nmol/L.