코로나 19 환자에서 발생하는 사이토카인 폭풍을 억제하는 비타민 D - 2020년 4월 8일 최신논문

[문형철]

beyond reason

https://www.medrxiv.org/content/10.1101/2020.04.08.20058578v4.full.pdf

 CRP is a surrogate marker for cytokine storm and is associated with Vit D deficiency, based on retrospective data and indirect evidence we see a possible role of Vit D in reducing complications attributed to unregulated inflammation and cytokine storm.

- CRP(c-reactive protein)은 사이토카인 폭풍의 마커이고 비타민  D 결핍증과 관련되어 있음. 

  비타민 D는 사이토카인 폭풍과 조절되지 않는 염증으로 인한 합병증을 줄임.

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

Ali Daneshkhah, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman

doi: https://doi.org/10.1101/2020.04.08.20058578 

This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be eval‎uated and so should not be used to guide clinical practice.

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Abstract

Objectives 

To investigate the possible role of Vitamin D (Vit D) deficiency via unregulated inflammation in COVID-19 complications and associated mortality. 

Design 

The time-adjusted case mortality ratio (T-CMR) was estimated as the number of deceased patients on day N divided by the number of confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was further calculated as a metric of COVID-19 associated mortality in different countries. A model based on positivity change (PC) and an estimated preval‎ence of COVID-19 was developed to determine countries with similar screening strategies. Mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategies were compared to investigate the potential impact of Vit D on A-CMR. 

We analyzed data showing a possible association between high C-Reactive Protein (CRP) concentration (CRP greater than or equal to 1 mg/dL) and severe COVID-19. We estimated a link between Vit D status and high CRP in healthy subjects (CRP greater than or equal to 0.2 mg/dL) with an adjustment for age and income to explore the possible role of Vit D in reducing complications attributed to unregulated inflammation and cytokine production. 

Data Sources 

Daily admission, recovery, and deceased rate data for patients with COVID-19 were collected from Kaggle as of April 20, 2020. Screening data were collected from Our World in Data and official statements from public authorities. The mean concentration of 25(OH)D among the elderly for comparison with A-CMR was collected from previously published studies from different countries. Chronic factor data used in regression analysis was obtained from published articles. The correlation between Vit D and CRP was calculated based on 9,212 subject-level data from NHANES, 2009-2010. 

Results 

A link between 25(OH)D and A-CMR in the US, France, Iran and the UK (countries with similar screening status) may exist. We observed an inverse correlation (correlation coefficient ranging from -0.84 to -1) between high CRP and 25(OH)D. Age and the family income status also correlated to high CRP and subjects with higher age and lower family income presented more incidences of high CRP. Our analysis determined a possible link between high CRP and Vit D deficiency and calculated an OR of 1.8 with 95%CI (1.2 to 2.6) among the elderly (age greater than or equal to 60 yo) in low-income families and an OR of 1.9 with 95%CI (1.4 to 2.7) among the elderly (age greater than or equal to 60 yo) in high-income families. COVID-19 patient-level data shows a notable OR of 3.4 with 95%CI (2.15 to 5.4) for high CRP in severe COVID-19 patients. 

Conclusion 

Given that CRP is a surrogate marker for cytokine storm and is associated with Vit D deficiency, based on retrospective data and indirect evidence we see a possible role of Vit D in reducing complications attributed to unregulated inflammation and cytokine storm. Further research is needed to account for other factors through direct measurement of Vit D levels in COVID-19 patients.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The authors would like to thank Benjamin D Keane for his assistance in preparing the manuscript. The authors would also like to acknowledge generous support from the Carinato Charitable Foundation, Mark and Ingeborg Holliday, Kristin Hudson & Rob Goldman, and Ms. Susan Brice & Mr. Jordi Esteve.

Author Declarations

All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.

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All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm‎ that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.