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

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

doi:10.1093/infdis/jiab065

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

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. DofferhoffMarjan 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

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1322-1333
Number of pages	12
Journal	The Journal of infectious diseases
Volume	223
Issue number	8
DOIs	https://doi.org/10.1093/infdis/jiab065
Publication status	Published - 15 Apr 2021
Externally published	Yes

Keywords

adaptive immunity
biomarkers
COVID-19
cytokines
disease severity
exhaustion markers
flow cytometry
innate immunity
proteomics

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10.1093/infdis/jiab065

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Janssen, N. A. F., Grondman, I., De Nooijer, A. H., Boahen, C. K., Koeken, V. A. C. M., Matzaraki, V., Kumar, V., He, X., Kox, M., Koenen, H. J. P. M., Smeets, R. L., Joosten, I., Brüggemann, R. J. M., Kouijzer, I. J. E., Van Der Hoeven, H. G., Schouten, J. A., Frenzel, T., Reijers, M. H. E., Hoefsloot, W., ... Van De Veerdonk, F. L. (2021). Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19. The Journal of infectious diseases, 223(8), 1322-1333. https://doi.org/10.1093/infdis/jiab065

@article{cf836766a1694512a0a38f351f1830a2,

title = "Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19",

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 = "adaptive immunity, biomarkers, COVID-19, cytokines, disease severity, exhaustion markers, flow cytometry, innate immunity, proteomics",

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

year = "2021",

month = apr,

day = "15",

doi = "10.1093/infdis/jiab065",

language = "English",

volume = "223",

pages = "1322--1333",

journal = "The Journal of infectious diseases",

issn = "1537-6613",

publisher = "Oxford University Press",

number = "8",

}

Janssen, NAF, Grondman, I, De Nooijer, AH, Boahen, CK, Koeken, VACM, Matzaraki, V, Kumar, V, He, X, Kox, M, Koenen, HJPM, Smeets, RL, Joosten, I, Brüggemann, RJM, Kouijzer, IJE, Van Der Hoeven, HG, Schouten, JA, Frenzel, T, Reijers, MHE, Hoefsloot, W, Dofferhoff, ASM, Van Apeldoorn, MJ, Blaauw, MJT, Veerman, K, Maas, C, Schoneveld, AH, Hoefer, IE, Derde, LPG, Van Deuren, M, Van Der Meer, JWM, Van Crevel, R, Giamarellos-Bourboulis, EJ, Joosten, LAB, Van Den Heuvel, MM, Hoogerwerf, J, De Mast, Q, Pickkers, P, Netea, MG & Van De Veerdonk, FL 2021, 'Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19', The Journal of infectious diseases, vol. 223, no. 8, pp. 1322-1333. https://doi.org/10.1093/infdis/jiab065

TY - JOUR

T1 - Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19

AU - Janssen, Nico A.F.

AU - Grondman, Inge

AU - De Nooijer, Aline H.

AU - Boahen, Collins K.

AU - Koeken, Valerie A.C.M.

AU - Matzaraki, Vasiliki

AU - Kumar, Vinod

AU - He, Xuehui

AU - Kox, Matthijs

AU - Koenen, Hans J.P.M.

AU - Smeets, Ruben L.

AU - Joosten, Irma

AU - Brüggemann, Roger J.M.

AU - Kouijzer, Ilse J.E.

AU - Van Der Hoeven, Hans G.

AU - Schouten, Jeroen A.

AU - Frenzel, Tim

AU - Reijers, Monique H.E.

AU - Hoefsloot, Wouter

AU - Dofferhoff, Anton S.M.

AU - Van Apeldoorn, Marjan J.

AU - Blaauw, Marc J.T.

AU - Veerman, Karin

AU - Maas, Coen

AU - Schoneveld, Arjan H.

AU - Hoefer, Imo E.

AU - Derde, Lennie P.G.

AU - Van Deuren, Marcel

AU - Van Der Meer, Jos W.M.

AU - Van Crevel, Reinout

AU - Giamarellos-Bourboulis, Evangelos J.

AU - Joosten, Leo A.B.

AU - Van Den Heuvel, Michel M.

AU - Hoogerwerf, Jacobien

AU - De Mast, Quirijn

AU - Pickkers, Peter

AU - Netea, Mihai G.

AU - Van De Veerdonk, Frank L.

PY - 2021/4/15

Y1 - 2021/4/15

N2 - 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.

AB - 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.

KW - adaptive immunity

KW - biomarkers

KW - COVID-19

KW - cytokines

KW - disease severity

KW - exhaustion markers

KW - flow cytometry

KW - innate immunity

KW - proteomics

UR - http://www.scopus.com/inward/record.url?scp=85105762172&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiab065

DO - 10.1093/infdis/jiab065

M3 - Article

C2 - 33524124

AN - SCOPUS:85105762172

SN - 1537-6613

VL - 223

SP - 1322

EP - 1333

JO - The Journal of infectious diseases

JF - The Journal of infectious diseases

IS - 8

ER -

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

Abstract

Keywords

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