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

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

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

Author(s) -

Nico Janssen,

Inge Grondman,

Aline 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 Schouten,

Tim Frenzel,

Monique H. 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 Derde,

Marcel van Deuren,

J.W.M. van der Meer,

Reinout van Crevel,

Evangelos J. GiamarellosBourboulis,

Leo A. B. Joosten,

Michel M. van den Heuvel,

Jacobien J. Hoogerwerf,

Quirijn de Mast,

Peter Pickkers,

Mihai G. Netea,

Frank L. van de Veerdonk

Publication year - 2021

Publication title -

the journal of infectious diseases

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.69

H-Index - 252

eISSN - 1537-6613

pISSN - 0022-1899

DOI - 10.1093/infdis/jiab065

Subject(s) - immunology , immune system , cytokine , cytokine storm , immune dysregulation , acquired immune system , medicine , innate immune system , proinflammatory cytokine , flow cytometry , interleukin , peripheral blood mononuclear cell , disease , biology , inflammation , covid-19 , infectious disease (medical specialty) , biochemistry , in vitro

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.

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