Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients

• Published in: Aging clinical and experimental research Vol. 32; no. 10; pp. 2141 - 2158
• Main Authors: Daneshkhah, Ali, Agrawal, Vasundhara, Eshein, Adam, Subramanian, Hariharan, Roy, Hemant Kumar, Backman, Vadim
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2020; Springer Nature B.V
• Subjects: Aged; Betacoronavirus - immunology; Betacoronavirus - pathogenicity; C-reactive protein; C-Reactive Protein - analysis; Coronavirus Infections - epidemiology; Coronavirus Infections - immunology; Coronavirus Infections - mortality; Coronaviruses; COVID-19; Cytokine storm; Cytokines; Cytokines - immunology; Female; Geriatrics/Gerontology; Humans; Inflammation; Inflammation - immunology; Male; Medicine; Medicine & Public Health; Middle Aged; Mortality; Original; Original Article; Pandemics; Pneumonia, Viral - epidemiology; Pneumonia, Viral - immunology; Pneumonia, Viral - mortality; SARS-CoV-2; Vitamin D - immunology; Vitamin D - therapeutic use; COVID-19; SARS-CoV-2; Case mortality ratio; C-reactive protein; Vitamin D; Cytokine storm
• ISSN: 1720-8319; 1594-0667; 1720-8319
• DOI: 10.1007/s40520-020-01677-y

Objectives We present evidence for a possible role of Vitamin D (VitD) deficiency in unregulated cytokine production and inflammation leading to complications in COVID-19 patients. Design The time-adjusted case mortality ratio (T-CMR) was estimated as the ratio of deceased patients on day N to the confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was calculated as a metric of COVID-19 associated mortality. A model based on positivity change (PC) and an estimated prevalence of COVID-19 was used to determine countries with similar screening strategies. A possible association of A-CMR with the mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategy was investigated. We considered high C-reactive protein (CRP) in severe COVID-19 patients (CRP ≥ 1 mg/dL) as a surrogate of a cytokine storm. We considered high-sensitivity CRP (hs-CRP) in healthy subjects as hs-CRP ≥ 0.2 mg/dL. Results A link between 25(OH)D and A-CMR in countries with similar screening strategy is evidence for VitD’s possible role in reducing unregulated cytokine production and inflammation among patients with severe COVID-19. We observed an odds ratio (OR) of 1.8 with 95% confidence interval (95% CI) (1.2 to 2.6) and an OR of 1.9 with 95% CI (1.4 to 2.7) for hs-CRP in VitD deficient elderly from low-income families and high-income families, respectively. COVID-19 patient-level data show an OR of 3.4 with 95% CI (2.15 to 5.4) for high CRP in severe COVID-19 patients. Conclusion We conclude that future studies on VitD’s role in reducing cytokine storm and COVID-19 mortality are warranted.