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. 2021 Mar 7;31(4):154–167. doi: 10.1684/ecn.2020.0456

Extensive longitudinal immune profiling reveals sustained innate immune activaton in COVID-19 patients with unfavorable outcome

Benjamin Schrijver 1, Jorn L J C Assmann 1, Adriaan J van Gammeren 2, Roel C H Vermeulen 3, Lützen Portengen 3, Peter Heukels 4, Anton W Langerak 1, Willem A Dik 1, Vincent H J van der Velden 1,✉, Ton A A M Ermens 2
PMCID: PMC7937051  PMID: 33648924

Abstract

COVID-19 differs substantially between individuals, ranging from mild to severe or even fatal. Heterogeneity in the immune response against SARS-COV-2 likely contributes to this. Therefore, we explored the temporal dynamics of key cellular and soluble mediators of innate and adaptive immune activation in relation to COVID-19 severity and progression.

Forty-four patients with a PCR-proven diagnosis of COVID-19 were included. Extensive cellular (leukocytes and T-lymphocyte subsets) and serological immune profiling (cytokines, soluble cell surface molecules, and SARS-CoV-2 antibodies) was performed at hospital admission and every 3–4 days during hospitalization. Measurements and disease outcome were compared between patients with an unfavorable (IC admission and/or death) and favorable (all others) outcome.

Patients with an unfavorable outcome had higher leukocyte numbers at baseline, mostly due to increased neutrophils, whereas lymphocyte and monocyte numbers were reduced. CRP, IL-6, CCL2, CXCL10, and GM-CSF levels were higher at baseline in the unfavorable group, whereas IL-7 levels were lower. SARS-CoV-2 antibodies were more frequently absent in the unfavorable group. Longitudinal analysis revealed delayed kinetics of activated CD4 and CD8 T-lymphocyte subsets in the unfavorable group. Furthermore, whereas CRP, IL-6, CXCL10, and GM-CSF declined in the favorable group, these cytokines declined with delayed kinetics, remained increased, or even increased further in the unfavorable group.

Our data indicate a state of increased innate immune activation in COVID19-patients with an unfavorable outcome at hospital admission, which remained over time, as compared with patients with a favorable outcome.

Key words: COVID-19, SARS-CoV-2

Acknowledgements

We gratefully acknowledge Ms R. van Rijckevorsel for performing all flowcytometric analyses. We gratefully acknowledge Ms Nicole Nagtzaam and Ms Marja Smits-te Nijenhuis for their technical support.

Author contributions

B.S. and J.L.J.C. performed the experiments, analyzed the data, interpreted results, and wrote the manuscript; A.J.G., P.H. and T.A.A.M.E. collected the samples, interpreted results, and helped writing the manuscript; R.C.H.V. and L.P. performed the statistical analyses and helped writing the manuscript; A.W.L., W.A. D., and V.H.J.V. designed the study, interpreted results, and helped writing the manuscript. Conflicts of interest: none.

Footnotes

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Data sharing statement

The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethical statement: The study was performed in accordance with the guidelines for sharing of patient data of observational scientific research in case of exceptional health situations, as issued by the Commission on Codes of Conduct of the Foundation Federation of Dutch Medical Scientific Societies (https://www.federa.org/federa-english).

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