1. Distinct cytokine profiles associated with COVID-19 severity and mortality
- Author
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Christophe Parizot, Matthieu Schmidt, Hans Yssel, Alexis Mathian, Mehmet Gökkaya, Loïc Le Guennec, Christophe Combadière, Karim Dorgham, Claudia Traidl-Hoffmann, Guillaume Voiriot, Amélie Guihot, Sophie Demeret, Sonia Burrel, Guy Gorochov, Delphine Sauce, Elyes Ben Salah, Paul Quentric, Stéphane Marot, Avidan U. Neumann, Zahir Amoura, Charles-Edouard Luyt, Anne-Geneviève Marcelin, Alexandra Beurton, Béhazine Combadière, Julien Mayaux, Centre d'Immunologie et de Maladies Infectieuses (CIMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Male ,principal component analysis ,medicine.medical_treatment ,SAPS-II, simplified acute physiology score ,Gastroenterology ,Severity of Illness Index ,0302 clinical medicine ,Immunology and Allergy ,030212 general & internal medicine ,Respiratory system ,Simplified Acute Physiology Score ,ComputingMilieux_MISCELLANEOUS ,COVID-19, coronavirus disease 2019 ,TNF, tumor necrosis factor ,Covid-19 ,Mortality ,Principal Component Analysis ,Respiratory Severity ,Serum Cytokines ,Type-i Ifns ,Middle Aged ,ALQ, above upper limit of quantification ,3. Good health ,Cytokine ,SAPS II ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Cytokines ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Adult ,medicine.medical_specialty ,Immunology ,type-I IFNs ,Ag, antigen ,serum cytokines ,SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 ,Article ,Proinflammatory cytokine ,03 medical and health sciences ,Internal medicine ,Severity of illness ,medicine ,Extracorporeal membrane oxygenation ,Humans ,IFN, interferon ,ddc:610 ,fCC, cytokine combination function ,MVS, mechanical ventilatory support ,Aged ,PCA, principal component analysis ,business.industry ,SARS-CoV-2 ,COVID-19 ,respiratory severity ,mortality ,Respiration, Artificial ,IL, interleukin ,030104 developmental biology ,Relative risk ,business ,ECMO, extracorporeal membrane oxygenation - Abstract
Background Markedly elevated levels of pro-inflammatory cytokines and defective type-I interferon responses were reported in COVID-19 patients. Objective This study aimed to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Methods Cytokine concentrations and SARS-CoV-2 antigen were measured at hospital admission in serum of symptomatic COVID-19 patients (N=115), classified at hospitalization into three respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS) and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N=86). Results At time of hospitalization, ECMO patients presented a dominant pro-inflammatory response with elevated levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at one month was associated with higher levels of pro-inflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (Risk Ratio 24.3, p, Graphical abstract, Capsule SummaryDistinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality in different oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.
- Published
- 2021
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