Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19. (1st February 2021)

• Record Type: Journal Article
• Authors: 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;
• Is Part Of: Journal of infectious diseases. Volume 223:Number 8(2021)
• Page Start: 1322
• Page End: 1333
• Publication Date: 2021-02-01
• Subjects: COVID-19 -- disease severity -- biomarkers -- cytokines -- proteomics -- innate immunity -- adaptive immunity -- flow cytometry -- exhaustion markers; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab065
• Languages: English
• ISSNs: 0022-1899

Abstract

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. Abstract : Increasing COVID-19 disease severity is characterized by higher circulating levels of inflammatory markers, differential expression of HGF (higher) and SCF (lower), a hyperinflammatory innate immune system, and a severely dysfunctional adaptive immune system.