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

• Published in: European cytokine network (Montrouge) 2020-12, Vol.31 (4), p.154-167
• Main Authors: Schrijver, Benjamin, Assmann, Jorn L.J.C., van Gammeren, Adriaan J., Vermeulen, Roel C.H., Portengen, Lützen, Heukels, Peter, Langerak, Anton W., Dik, Willem A., van der Velden, Vincent H.J., Ermens, Ton A.A.M.
• Format: Article
• Language: English
• Subjects: Antibodies; CD4 antigen; CD8 antigen; Cell surface; Coronaviruses; COVID-19; CXCL10 protein; Cytokines; Granulocyte-macrophage colony-stimulating factor; Immune response; Interleukin 6; Interleukin 7; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Monocyte chemoattractant protein 1; Monocytes; Original; Severe acute respiratory syndrome coronavirus 2
• ISSN: 1148-5493; 1952-4005
• DOI: 10.1684/ecn.2020.0456

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.