Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19
Janssen, Nico A.F.; Grondman, Inge; de Nooijer, Aline H.; Boahen, Collins K.; Koeken, Valerie A.C.M.; Matzaraki, Vasiliki; Kumar, Vinod; He, Xuehui; Kox, Matthijs; Koenen, Hans J.P.M.; Smeets, Ruben L.; Joosten, Irma; Brüggemann, Roger J.M.; Kouijzer, Ilse J.E.; van der Hoeven, Hans G.; Schouten, Jeroen A.; Frenzel, Tim; Reijers, Monique H.E.; Hoefsloot, Wouter; Dofferhoff, Anton S.M.; van Apeldoorn, Marjan J.; Blaauw, Marc J.T.; Veerman, Karin; Maas, Coen; Schoneveld, Arjan H.; Hoefer, Imo E.; Derde, Lennie P.G.; van Deuren, Marcel; van der Meer, Jos W.M.; van Crevel, Reinout; Giamarellos-Bourboulis, Evangelos J.; Joosten, Leo A.B.; van den Heuvel, Michel M.; Hoogerwerf, Jacobien; de Mast, Quirijn; Pickkers, Peter; Netea, Mihai G.; van de Veerdonk, Frank L.
(2021) The Journal of infectious diseases, volume 223, issue 8, pp. 1322 - 1333
(Article)
Abstract
The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive proinflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147
... read more
COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis revealed no specific inflammatory endotypes in COVID-19 patients. Functional assays revealed abrogated adaptive cytokine production (interferon-γ, interleukin-17, and interleukin-22) and prominent T-cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlights potential biomarkers of disease severity.
show less
Download/Full Text
The full text of this publication is not available.
Keywords: adaptive immunity, biomarkers, COVID-19, cytokines, disease severity, exhaustion markers, flow cytometry, innate immunity, proteomics, Humans, Middle Aged, Cytokines/immunology, Male, COVID-19/blood, Lymphopenia/blood, Inflammation/blood, Biomarkers/blood, Female, Cytokine Release Syndrome/blood, Severity of Illness Index, Immunity, Innate/immunology, Adaptive Immunity/immunology, SARS-CoV-2/immunology, Leukocytes, Mononuclear/immunology, Aged, Infectious Diseases, Immunology and Allergy, Journal Article
ISSN: 0022-1899
Publisher: Oxford University Press
Note: Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
(Peer reviewed)