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

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, andGM-CSF declinedin 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.