Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis

• Published in: PloS one Vol. 17; no. 7; p. e0268396
• Main Authors: D'Ecclesiis, Oriana, Gavioli, Costanza, Martinoli, Chiara, Raimondi, Sara, Chiocca, Susanna, Miccolo, Claudia, Bossi, Paolo, Cortinovis, Diego, Chiaradonna, Ferdinando, Palorini, Roberta, Faciotti, Federica, Bellerba, Federica, Canova, Stefania, Jemos, Costantino, Salé, Emanuela Omodeo, Gaeta, Aurora, Zerbato, Barbara, Gnagnarella, Patrizia, Gandini, Sara
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 06.07.2022; Public Library of Science (PLoS)
• Subjects: Alfacalcidol; Calcifediol; Calciferol; Clinical trials; Coronaviruses; COVID-19; Dietary supplements; Earth Sciences; Enzymes; Estimates; Fatalities; Health aspects; Health risks; Infections; Intensive care; Intubation; Mechanical ventilation; Medical ethics; Medical research; Medicine and Health Sciences; Meta-analysis; Mortality; Pandemics; Patients; Physical Sciences; Quality assessment; Research and Analysis Methods; Respiratory distress syndrome; Risk; Science Policy; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; Systematic review; Ventilation; Viral diseases; Viral infections; Vitamin D; Vitamin deficiency; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0268396

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.