Open Access

ORIGINAL ARTICLE

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

Benjamin Schrijver^1,a, Jorn L. J. C. Assmann^1,a, Adriaan J. van Gammeren², Roel C. H. Vermeulen³, Lützen Portengen³, Peter Heukels⁴, Anton W. Langerak¹, Willem A. Dik¹, Vincent H. J. van der Velden^1,b, Ton A. A. M. Ermens^2,b

1 Department of Immunology, Laboratory Medical Immunology, Erasmus MC-University Medical Center Rotterdam, the Netherlands
2 Department of Clinical Chemistry and Hematology, Amphia Hospital, Breda, the Netherlands
3 Department of Population Health Sciences, Institute for Risk Assessment Sciences, University Utrecht, Utrecht, the Netherlands
4 Department of Pulmonology, Amphia Hospital, Breda, the Netherlands
a Shared first author
b Shared last author

* Corresponding Author: Vincent H.J. van der Velden

European Cytokine Network 2020, 31(4), 154-167. https://doi.org/10.1684/ecn.2020.0456

Accepted 16 October 2020;

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 COVID-19 patients with an unfavorable outcome at hospital admission, which remained over time, as compared with patients with a favorable outcome.

---

Keywords

---