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. 2021 Apr 23;223(8):1322-1333.
doi: 10.1093/infdis/jiab065.

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

Nico A F Janssen  1 , Inge Grondman  1 , Aline H de Nooijer  1 , Collins K Boahen  1 , Valerie A C M Koeken  1 , Vasiliki Matzaraki  1 , Vinod Kumar  1   2 , Xuehui He  3 , Matthijs Kox  4 , Hans J P M Koenen  3 , Ruben L Smeets  3   5 , Irma Joosten  3 , Roger J M Brüggemann  6 , Ilse J E Kouijzer  1 , Hans G van der Hoeven  4 , Jeroen A Schouten  4 , Tim Frenzel  4 , Monique H E Reijers  7 , Wouter Hoefsloot  7 , Anton S M Dofferhoff  8 , Marjan J van Apeldoorn  9 , Marc J T Blaauw  10 , Karin Veerman  11 , Coen Maas  12 , Arjan H Schoneveld  12 , Imo E Hoefer  12 , Lennie P G Derde  13 , Marcel van Deuren  1 , Jos W M van der Meer  1 , Reinout van Crevel  1 , Evangelos J Giamarellos-Bourboulis  14 , Leo A B Joosten  1 , Michel M van den Heuvel  7 , Jacobien Hoogerwerf  1 , Quirijn de Mast  1 , Peter Pickkers  4 , Mihai G Netea  1   15 , Frank L van de Veerdonk  1
Affiliations

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

Nico A F Janssen et al. J Infect Dis. .

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 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.

Keywords: COVID-19; adaptive immunity; biomarkers; cytokines; disease severity; exhaustion markers; flow cytometry; innate immunity; proteomics.

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