The Role of Vitamin D in Suppressing Cytokine Storm in COVID-19 Patients and Associated Mortality

Ali Daneshkhah, et al. 2020, in press MedRxiv
Department of Biomedical Engineering, Northwestern University

Statistical analysis of data obtained from hospitals and clinics across the world has been analyzed to illuminate new insights into characteristics of COVID-19 and to discern whether a link exists between severe cases of COVID-19 that feature cytokine storm and vitamin D (Vit D) deficiency.

Daily admission, recovery and deceased rate data for patients with COVID-19 from countries with over 5,000 confirmed cases through March 21, 2020, were selected. A potential association between severe Vit D deficiency and age-specific case fatality (CFR) was investigated. Reported medical characteristics of 793 COVID-19 patients were used to evaluate the intensity of cytokine storm in severe COVID-19 using C-reactive protein (CRP) levels. Medical data reported from a national study of 3,848 participants in 2007-2008 was used to investigate the association between Vit D status and CRP. Odds ratio and risk factors from these conditions were used to predict the potential impact of Vit D on the reduction of cytokine storm and severe COVID-19.
Age-specific CFR in Italy, Spain, and France (70 yo ≤ age < 80 yo) was substantially higher (>1.9 times) than other countries (Germany, South Korea, China); for the elderly (age ≥70 yo), Italy and Spain present the highest CFR (>1.7 times that of other countries). The age-specific ratio of confirmed cases in Italy, Spain, and France has also been substantially higher than in other countries. A more severe deficiency of Vit D (mean 25- hydroxyvitamin D (25OHD) concentration <0.25 ng/L) is reported in Italy and Spain compared to other countries. Our analysis of the reported clinical data (25OHD, CRP) from multiple studies suggests that elimination of severe Vit D deficiency reduces the risk of high CRP levels (odds ratio of 2) which may be used as a surrogate marker of cytokine storm which was estimated to a potential reduction in severe COVID-19 cases of up to 15%.

StarPower Summary: Those that experience the most adverse outcomes with covid-19 are vitamin D deficient.


2015 Jul;70(7):617-24. doi: 10.1136/thoraxjnl-2014-206680. Epub 2015 Apr 22.

Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS).



Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated.


To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity.


Human, murine and in vitro primary alveolar epithelial cell work were included in this study.


Vitamin D deficiency (plasma 25(OH)D levels <50 nmol/L) was ubiquitous in patients with ARDS and present in the vast majority of patients at risk of developing ARDS following oesophagectomy. In a murine model of intratracheal lipopolysaccharide challenge, dietary-induced vitamin D deficiency resulted in exaggerated alveolar inflammation, epithelial damage and hypoxia. In vitro, vitamin D has trophic effects on primary human alveolar epithelial cells affecting >600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients.


Vitamin D deficiency is common in people who develop ARDS. This deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed.

StarPower Summary: Those that experience acute respiratory distress syndrome are vitamin D deficient