Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patie
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ORIGINAL ARTICLE
Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID‑19 patients Ali Daneshkhah1 · Vasundhara Agrawal1 · Adam Eshein1 · Hariharan Subramanian1 · Hemant Kumar Roy2 · Vadim Backman1 Received: 20 June 2020 / Accepted: 4 August 2020 © The Author(s) 2020
Abstract 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. Keywords COVID-19 · Vitamin D · Cytokine storm · C-reactive protein · Case mortality ratio · SARS-CoV-2
Introduction The recent global outbreak of COVID-19 imposed catastrophic impacts on every society, specifically among elderly populations. Currently, no treatment or vaccine against the virus is available. Consequently there is a significant need to elucidate potential approaches that can reduce the number of severe COVID-19 cases and associated mortality. Large-scale data show that the mortality rate of COVID19 varies dramatically across countries. For example, a
* Vadim Backman v‑[email protected] 1
Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA
Boston Medical Center, Boston, MA, USA
2
higher case fatality ratio has been reported in Spain, Italy, and the UK compared to that in the US and Germany. The cause for these disparities is not well understood. Several hypotheses have been proposed, including the emergence and circulation of different strains of the virus [1–3], idiosyncrasies in COVID-19 testi
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