Journal article
Differential Cytokine Signatures of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Influenza Infection Highlight Key Differences in Pathobiology
Clinical infectious diseases, Vol.74(2), pp.254-262
01/29/2022
DOI: 10.1093/cid/ciab376
PMCID: PMC8243556
PMID: 34013339
Abstract
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.
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.
Interleukin-18 (IL-18), IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were significantly increased in COVID-19 versus influenza patients, whereas granulocyte macrophage colony-stimulating factor, interferon-γ (IFN-γ), IFN-λ1, 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-α were elevated in severe COVID-19, but not in severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 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.
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.
Details
- Title: Subtitle
- Differential Cytokine Signatures of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Influenza Infection Highlight Key Differences in Pathobiology
- Creators
- Andrew H Karaba - Johns Hopkins University School of MedicineWeiqiang Zhou - Johns Hopkins UniversityLeon L Hsieh - Johns Hopkins University School of MedicineAlexis Figueroa - Johns Hopkins University School of MedicineGuido Massaccesi - Johns Hopkins University School of MedicineRichard E Rothman - Johns Hopkins University School of MedicineKatherine Z J Fenstermacher - Johns Hopkins University School of MedicineLauren Sauer - Johns Hopkins University School of MedicineKathryn Shaw-Saliba - Johns Hopkins University School of MedicinePaul W Blair - Johns Hopkins University School of MedicineMatthew L Robinson - Johns Hopkins University School of MedicineSherry Leung - Johns Hopkins University School of MedicineRussell Wesson - Johns Hopkins University School of MedicineNada Alachkar - Johns Hopkins University School of MedicineRamy El-Diwany - Johns Hopkins University School of MedicineHongkai Ji - Johns Hopkins UniversityAndrea L Cox - Johns Hopkins University School of Medicine
- Resource Type
- Journal article
- Publication Details
- Clinical infectious diseases, Vol.74(2), pp.254-262
- DOI
- 10.1093/cid/ciab376
- PMID
- 34013339
- PMCID
- PMC8243556
- NLM abbreviation
- Clin Infect Dis
- ISSN
- 1058-4838
- eISSN
- 1537-6591
- Grant note
- Health Careers Opportunity Program Human Services Biomedical Advanced Research HHSN272201400007C / NIAID NIH HHS U19 AI088791 / NIAID NIH HHS U19AI088791 / National Institute of Allergy and Infectious Diseases T32 GM136577 / NIGMS NIH HHS U54CA260491 / NCI NIH HHS US Department of Health R01HG009518 / NIH HHS Bureau of Health Workforce
- Language
- English
- Date published
- 01/29/2022
- Academic Unit
- Surgery
- Record Identifier
- 9984966857602771
Metrics
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