Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis
Oriana D’ecclesiis, Costanza Gavioli, Chiara Martinoli, Sara Raimondi, Susanna Chiocca, Claudia Miccolo, Paolo Bossi, Diego Cortinovis, Ferdinando Chiaradonna, Roberta Palorini, Federica Faciotti, Federica Bellerba, Stefania Canova, Costantino Jemos, Emanuela Omodeo Salé, Aurora Gaeta, Barbara Zerbato, Patrizia Gnagnarella, Sara Gandini
PLOS ONE, 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.
Author Contributions Conceptualization: Susanna Chiocca, Patrizia Gnagnarella, Sara Gandini.
Data curation: Oriana D'Ecclesiis, Costanza Gavioli, Chiara Martinoli, Aurora Gaeta, Barbara Zerbato. Formal analysis: Oriana D'Ecclesiis, Federica Bellerba, Aurora Gaeta, Barbara Zerbato, Sara Gandini. Funding acquisition: Susanna Chiocca, Paolo Bossi, Diego Cortinovis, Ferdinando Chiaradonna, Sara Gandini. Investigation: Oriana D'Ecclesiis, Chiara Martinoli, Patrizia Gnagnarella, Sara Gandini. Methodology: Oriana D'Ecclesiis, Costanza Gavioli, Chiara Martinoli, Sara Raimondi, Sara Gandini. Project administration: Susanna Chiocca, Sara Gandini. Resources: Susanna Chiocca, Paolo Bossi, Diego Cortinovis, Ferdinando Chiaradonna, Sara Gandini. Software: Oriana D'Ecclesiis. Supervision: Sara Raimondi, Susanna Chiocca, Patrizia Gnagnarella, Sara Gandini. Validation: Sara Raimondi, Stefania Canova, Aurora Gaeta, Barbara Zerbato, Patrizia Gnagnarella. Visualization: Oriana D'Ecclesiis, Federica Bellerba, Sara Gandini. Writing -original draft: Oriana D'Ecclesiis, Chiara Martinoli, Barbara Zerbato, Sara Gandini. Writing -review & editing: Costanza Gavioli, Chiara Martinoli, Sara Raimondi, Susanna Chiocca, Claudia Miccolo, Paolo Bossi, Diego Cortinovis, Ferdinando Chiaradonna, Roberta Palorini, Federica Faciotti, Federica Bellerba, Costantino Jemos, Emanuela Omodeo Sale ´, Barbara Zerbato, Patrizia Gnagnarella, Sara Gandini.
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'abstract': '<jats:p>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.</jats:p>',
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