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Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19.

The Journal of infectious diseases

Authors: Nico A F Janssen, Inge Grondman, Aline H de Nooijer, Collins K Boahen, Valerie A C M Koeken, Vasiliki Matzaraki, Vinod Kumar, Xuehui He, Matthijs Kox, Hans J P M Koenen, Ruben L Smeets, Irma Joosten, Roger J M Brüggemann, Ilse J E Kouijzer, Hans G van der Hoeven, Jeroen A Schouten, Tim Frenzel, Monique H E Reijers, Wouter Hoefsloot, Anton S M Dofferhoff, Marjan J van Apeldoorn, Marc J T Blaauw, Karin Veerman, Coen Maas, Arjan H Schoneveld, Imo E Hoefer, Lennie P G Derde, Marcel van Deuren, Jos W M van der Meer, Reinout van Crevel, Evangelos J Giamarellos-Bourboulis, Leo A B Joosten, Michel M van den Heuvel, Jacobien Hoogerwerf, Quirijn de Mast, Peter Pickkers, Mihai G Netea, Frank L van de Veerdonk

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 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.

© 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.

PMID: 33524124

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