Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics
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Abstract
Importance
Vitamin D deficiency increases the incidence of respiratory virus infections. More than 1 billion people worldwide are vitamin D deficient. If vitamin D deficiency is associated to incidence or severity of SARS-CoV-2 infection, a global call could be made for vitamin D supplementation to mitigate the pandemic.
Objective
to determine if lower serum 25-hydroxyvitamin D (25(OH)D) levels are correlated to the risk for COVID-19 and its severity as measured by CT
Design
single-center observational study
Setting
AZ Delta general hospital
Participants
186 consecutive patients with PCR-confirmed SARS-CoV-2 infection hospitalized for COVID-19 from March 1, 2020 to April 7, 2020
Main outcome and measures
comparative analysis of 25(OH)D levels in patients hospitalized for COVID-19 at various radiological stages and a season/age/sex-matched diseased control population
Results
we report on 186 SARS-CoV-2 infected patients requiring hospitalization for severe COVID-19: 109 males (median age 68 years, IQR 53–79 years) and 77 females (median age 71 years, IQR 65–74 years). At admission patients were screened by CT to determine temporal changes of COVID-19 lung disease and classified as stage 1 (ground glass opacities), 2 (crazy paving pattern) and 3 (consolidation). At intake, 25(OH)D levels were measured and compared to a season-matched population of 2717 diseased controls, consisting of 999 males (median age 69 years, IQR 53–81 years) and 1718 females (median age 68 years, IQR 43–83 years). Male and female COVID-19 patients combined showed lower median 25(OH)D than controls (18.6 ng/mL, IQR 12.6–25.3, versus 21.5 ng/mL, IQR 13.9–30.8; P=0.0016) and a higher fraction of vitamin D deficiency (58.6% versus 45.2%, P=0.0005). A strong sexual dimorphism was found: female patients had comparable vitamin D status as control females. Male COVID-19 patients, however, showed markedly higher percentage of vitamin D deficiency than controls (67.0% versus 49.2%, P=0.0006) and this effect was more pronounced with advanced radiological stage ranging from 55.2% in stage 1 to 74% in stage 3.
Conclusions and relevance
vitamin D deficiency is a possible risk factor for severe SARS-CoV-2 infection in males. Vitamin D supplementation might be an inexpensive, accessible and safe mitigation for the SARS-CoV-2 pandemic.
Key points
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Question: does vitamin D deficiency predispose to severity of SARS-CoV-2 infection?
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Findings: in this observational study on 186 consecutive patients hospitalized with PCR-confirmed SARS-CoV-2 infection, we find that patients with severe COVID-19 show lower median serum 25(OH)D and a higher percentage of vitamin D deficiency at intake than a season/age-matched reference population. The correlation between vitamin D deficiency and the need for hospitalization due to COVID-19 was only seen in male patients. In males but not females, the percentage of vitamin D deficient patients also increased with more advanced COVID-19 disease stage as measured by CT.
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Meaning: our data indicate a strong statistical correlation between the degree of vitamin D deficiency and severity of COVID-19 lung disease. With more than 1 billion people worldwide affected by vitamin D deficiency, vitamin D supplementation might be a lifesaving, inexpensive, accessible and safe component of primary prevention during the SARS-CoV-2 pandemic and beyond
Article activity feed
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SciScore for 10.1101/2020.05.01.20079376: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: This study was approved by the AZ Delta ethical committee (Clinical Trial Number IRB B1172020000009) with a waiver of informed consent from study participants considering the study is based on secondary analysis of existing data.
Consent: This study was approved by the AZ Delta ethical committee (Clinical Trial Number IRB B1172020000009) with a waiver of informed consent from study participants considering the study is based on secondary analysis of existing data.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistical analyses … SciScore for 10.1101/2020.05.01.20079376: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: This study was approved by the AZ Delta ethical committee (Clinical Trial Number IRB B1172020000009) with a waiver of informed consent from study participants considering the study is based on secondary analysis of existing data.
Consent: This study was approved by the AZ Delta ethical committee (Clinical Trial Number IRB B1172020000009) with a waiver of informed consent from study participants considering the study is based on secondary analysis of existing data.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistical analyses were performed using MedCalc (version 12.2.1, Mariakerke, Belgium) and considered significant if P value was less than .05. MedCalcsuggested: (MedCalc, RRID:SCR_015044)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.05.01.20079376: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement This study was approved by the AZ Delta ethical committee (Clinical Trial Number IRB B1172020000009) with a waiver of informed consent from study participants considering the study is based on secondary analysis of existing data. Randomization Several randomized controlled interventional trials with vitamin D supplementation for bone health or to reduce mortality in cardiovascular disease and cancer gave mixed or negative results, entailing a sense of indifference from the medical community towards the value of vitamin D monitoring and supplementation. Blinding not detected. Power Analysis not detected. Sex as a biological variable Males had lower median … SciScore for 10.1101/2020.05.01.20079376: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement This study was approved by the AZ Delta ethical committee (Clinical Trial Number IRB B1172020000009) with a waiver of informed consent from study participants considering the study is based on secondary analysis of existing data. Randomization Several randomized controlled interventional trials with vitamin D supplementation for bone health or to reduce mortality in cardiovascular disease and cancer gave mixed or negative results, entailing a sense of indifference from the medical community towards the value of vitamin D monitoring and supplementation. Blinding not detected. Power Analysis not detected. Sex as a biological variable Males had lower median 25(OH)D than females (22.3 ng/mL, IQR 14.9-31.3 versus 23.7 ng/mL, IQR 15.6-33.1, P<0.0001) and higher rates of vitamin D deficiency (42.0% versus 38.6%, P<0.0001) (Fig. 1A). Table 2: Resources
Results from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).
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