期刊
CLINICAL INFECTIOUS DISEASES
卷 74, 期 2, 页码 254-262出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciab376
关键词
COVID-19; Influenza; Cytokines; SARS-CoV-2; Obesity
资金
- Johns Hopkins COVID-19 Research Response Program
- Johns Hopkins University Provost Research Grant
- Bill and Melinda Gates Foundation [134582]
- National Cancer Institute [U54CA260491]
- National Institutes of Health Centers of Excellence in Influenza Research and Surveillance [HHSN272201400007C]
- Johns Hopkins University
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- US Department of Health and Human Services Biomedical Advanced Research and Development Authority [IDSEP160031-01-00]
- National Institute of Allergy and Infectious Diseases [HHSN272201400007C, U19AI088791, R01AI108403]
- National Institute of Health [R01HG009518, T32 AI007291-27]
- US Health Resources and Services Administration, Bureau of Health Workforce, Health Careers Opportunity Program [D18HP29037]
Severe COVID-19 is characterized by dysregulated inflammation and its association with elevated BMI. This study compared cytokines in COVID-19 and influenza patients, identifying different inflammatory pathways and a cytokine mediator of the effect of BMI.
Severe COVID-19 is marked by dysregulated inflammation and is associated with elevated BMI. By comparing cytokines and chemokines in patients with either COVID-19 or influenza, we identified distinct inflammatory pathways and a cytokine mediator of the effect of BMI. Background Several inflammatory cytokines are upregulated in severe coronavirus disease 2019 (COVID-19). We compared cytokines in COVID-19 versus influenza to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease. Methods Thirty-seven cytokines and chemokines were measured in plasma from 135 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was used to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was used to identify cytokines that mediate the effect of BMI and age on disease severity. Results Interleukin-18 (IL-18), IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were significantly increased in COVID-19 versus influenza patients, whereas granulocyte macrophage colony-stimulating factor, interferon-gamma (IFN-gamma), IFN-lambda 1, IL-10, IL-15, and monocyte chemoattractant protein 2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-alpha were elevated in severe COVID-19, but not in severe influenza. Random forest analysis identified high IL-6 and low IFN-lambda 1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity. Conclusions These findings point to activation of fundamentally different innate immune pathways in severe acute respiratory syndrome coronavirus 2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据