Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct;32(10):2141-2158.
doi: 10.1007/s40520-020-01677-y. Epub 2020 Sep 2.

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

Ali Daneshkhah  1 , Vasundhara Agrawal  1 , Adam Eshein  1 , Hariharan Subramanian  1 , Hemant Kumar Roy  2 , Vadim Backman  3
Affiliations

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

Ali Daneshkhah et al. Aging Clin Exp Res. 2020 Oct.

Erratum in

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: C-reactive protein; COVID-19; Case mortality ratio; Cytokine storm; SARS-CoV-2; Vitamin D.

PubMed Disclaimer

Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
a T-CMR (8 days) as of April 21. A 2-week variability (100 × (T-CMRApril 20 – T-CMRApril 6)/T-CMRApril 6) calculated at different T-CMR delays of 0 days, 8 days and 14 days. b A-CMR as of April 21 [26]. c Percentage of confirmed to tested ratio suggests an impact of screening strategy on A-CMR [32, 36]. France testing data are the number of tests [34]. England reported the number of tests (from April 1, 2020–April 21, 2020) and we estimated number tests before April 1, 2020 by multiplying the number of patients by 1.24 (the ratio obtained from average ratio of number of tests to the number of patients from April 1, 2020, to April 7, 2020 [33]. US data are mainly the number of people tested (some labs have reported the number of tests) [34]. Iran and Spain testing data are estimated from two reported statements by public authorities [–36]
Fig. 2
Fig. 2
PC over time compares growth rate of COVID-19
Fig. 3
Fig. 3
PC against rc for 2 weeks after each country reaches 10,000 patients (except S. Korea > 5,000 patients)
Fig. 4
Fig. 4
a Mean 25(OH)D in the elderly population in the US [61], Iran [62], France [63] and the UK [64]. Estimated 25(OH)D concentration of elderly in Italy [–51, 65], and Spain [52]. b A-CMR for the US, Iran, France, England, Italy, and Spain
Fig. 5
Fig. 5
Mean 25(OH)D concentration in the elderly population in Germany [53, 68], Switzerland [70] and S. Korea [54]
Fig. 6
Fig. 6
Regression analysis based on a 25(OH)D, b Diabetes prevalence among men and women (age-standardized), CHD death rate per 100,000 (age-standardized), and Elderly ratio (age ≥ 70 yo) in the countries with less aggressive screening strategy. c Regression analysis based on 25(OH)D in countries with more aggressive screening strategy
Fig. 7
Fig. 7
Age distribution of the a hospitalized, b admitted to ICU or deceased in Spain based on data from 145,429 cases [44]
Fig. 8
Fig. 8
Age distribution of the hospitalized in a the USA [37, 38], b Italy [40], c France [39], d the UK [43] and e Switzerland [41, 42]
Fig. 9
Fig. 9
a Estimated death rate among hospitalized elderly patients, b estimated concentration of 25(OH)D in elderly, c total number of confirmed cases in the country at the end of study interval and d number of critical beds per 100,000 population in the UK [43], Italy [40], Spain [44], France [39], and Iran [45]
Fig. 10
Fig. 10
High hs-CRP and possible low-grade inflammation association with VitD status
Fig. 11
Fig. 11
Possible impact of improving VitD status on the reduction of cytokines and CRP
See this image and copyright information in PMC

Comment in

  • Vitamin D status and COVID-19 in older adults.
    Mandal AKJ, Baktash V, Hosack T, Missouris CG. Mandal AKJ, et al. Aging Clin Exp Res. 2020 Nov;32(11):2425-2426. doi: 10.1007/s40520-020-01716-8. Epub 2020 Sep 21. Aging Clin Exp Res. 2020. PMID: 32955676 Free PMC article. No abstract available.

References

    1. Tang X, Wu C, Li X, et al. On the origin and continuing evolution of SARS-CoV-2. Natl Sci Rev. 2020 doi: 10.1093/nsr/nwaa036. - DOI - PMC - PubMed
    1. Yao H, Lu X, Chen Q, et al. Patient-derived mutations impact pathogenicity of SARS-CoV-2. medRxiv. 2020 doi: 10.1101/2020.04.14.20060160. - DOI - PubMed
    1. Coronavirus has mutated into 30 strains and ones in US are less deadlier than those in Europe, finds study. In: News Break. https://www.newsbreak.com/news/0OoSRJjb/coronavirus-has-mutated-into-30-.... Accessed 21 Apr 2020
    1. Dowd JB, Andriano L, Brazel DM, et al. Demographic science aids in understanding the spread and fatality rates of COVID-19. Proc Natl Acad Sci. 2020 doi: 10.1073/pnas.2004911117. - DOI - PMC - PubMed
    1. Kanchan T, Kumar N, Unnikrishnan B. Encyclopedia of forensic and legal medicine. Amsterdam: Elsevier Inc.; 2015. Mortality: statistics; pp. 572–577.

MeSH terms