PMID- 34013339
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20221110
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 74
IP  - 2
DP  - 2022 Jan 29
TI  - Differential Cytokine Signatures of Severe Acute Respiratory Syndrome Coronavirus 
      2 (SARS-CoV-2) and Influenza Infection Highlight Key Differences in Pathobiology.
PG  - 254-262
LID - 10.1093/cid/ciab376 [doi]
AB  - 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-1beta, 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-lambda1, 
      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-lambda1 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.
CI  - (c) The Author(s) 2021. Published by Oxford University Press for the Infectious 
      Diseases Society of America. All rights reserved. For permissions, e-mail: 
      journals.permissions@oup.com.
FAU - Karaba, Andrew H
AU  - Karaba AH
AD  - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Zhou, Weiqiang
AU  - Zhou W
AD  - Department of Biostatistics, Johns Hopkins University Bloomberg School of Public 
      Health, Baltimore, Maryland, USA.
FAU - Hsieh, Leon L
AU  - Hsieh LL
AD  - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Figueroa, Alexis
AU  - Figueroa A
AD  - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Massaccesi, Guido
AU  - Massaccesi G
AD  - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Rothman, Richard E
AU  - Rothman RE
AD  - Department of Emergency Medicine, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Fenstermacher, Katherine Z J
AU  - Fenstermacher KZJ
AD  - Department of Emergency Medicine, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Sauer, Lauren
AU  - Sauer L
AD  - Department of Emergency Medicine, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Shaw-Saliba, Kathryn
AU  - Shaw-Saliba K
AD  - Department of Emergency Medicine, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Blair, Paul W
AU  - Blair PW
AD  - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Robinson, Matthew L
AU  - Robinson ML
AD  - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Leung, Sherry
AU  - Leung S
AD  - Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Wesson, Russell
AU  - Wesson R
AD  - Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Alachkar, Nada
AU  - Alachkar N
AD  - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - El-Diwany, Ramy
AU  - El-Diwany R
AD  - Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Ji, Hongkai
AU  - Ji H
AD  - Department of Biostatistics, Johns Hopkins University Bloomberg School of Public 
      Health, Baltimore, Maryland, USA.
FAU - Cox, Andrea L
AU  - Cox AL
AUID- ORCID: 0000-0002-9331-2462
AD  - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
AD  - W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns 
      Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
AD  - Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
LA  - eng
GR  - R01 HG009518/HG/NHGRI NIH HHS/United States
GR  - Johns Hopkins University Provost Research/
GR  - U54CA260491/CA/NCI NIH HHS/United States
GR  - US Department of Health/
GR  - Johns Hopkins COVID-19 Research Response Program/
GR  - U19AI088791/National Institute of Allergy and Infectious Diseases/
GR  - US Health Resources and Services Administration/
GR  - 134582/The Bill and Melinda Gates Foundation/
GR  - Human Services Biomedical Advanced Research/
GR  - R01HG009518/NH/NIH HHS/United States
GR  - HHSN272201400007C/AI/NIAID NIH HHS/United States
GR  - U19 AI088791/AI/NIAID NIH HHS/United States
GR  - T32 AI007291/AI/NIAID NIH HHS/United States
GR  - T32 GM136577/GM/NIGMS NIH HHS/United States
GR  - Bureau of Health Workforce/
GR  - Health Careers Opportunity Program/
GR  - Johns Hopkins Center of Excellence in Influenza Research/
GR  - IDSEP160031-01-00/Development Authority/
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
SB  - IM
MH  - *COVID-19
MH  - Chemokines
MH  - Cytokines
MH  - Humans
MH  - *Influenza, Human
MH  - SARS-CoV-2
PMC - PMC8243556
OTO - NOTNLM
OT  - COVID-19
OT  - Cytokines
OT  - Influenza
OT  - Obesity
OT  - SARS-CoV-2
EDAT- 2021/05/21 06:00
MHDA- 2022/02/03 06:00
PMCR- 2022/05/20
CRDT- 2021/05/20 06:51
PHST- 2021/01/22 00:00 [received]
PHST- 2021/05/21 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/05/20 06:51 [entrez]
PHST- 2022/05/20 00:00 [pmc-release]
AID - 6278486 [pii]
AID - ciab376 [pii]
AID - 10.1093/cid/ciab376 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2022 Jan 29;74(2):254-262. doi: 10.1093/cid/ciab376.