Immune dysregulation in hospitalized COVID-19 patients is associated with worse clinical outcome

ABSTRACT

Background: COVID-19 is a viral disease affecting mostly respiratory system with variable severity of the clinical course. Several clinical and laboratory parameters are associated with poor outcome. Progression of the clinical stage is associated with the exaggerated immune response and the cytokine storm. Method(s) We focused on the search of potential prognostic markers of fatal outcome among immune parameters. To this end, we examined the immune profile in 823 COVID-19 patients hospitalized in University Teaching Hospital in Martin (Slovakia) on admission and its changes over time during the first week of hospitalization. The examined immune profile consisted of the differential blood cell counts, serum concentration of immunoglobulins and basic complement compounds C4 and C3, flow cytometric lymphocyte subsets phenotyping and the measurement of selected activation and inhibition markers. Result(s) Although none of examined parameters alone had sufficient AUC value to be considered as a marker of (un)favourable outcome, we found several significant differences among different severity groups of patients, as well as between survivors and non-survivors. Severity of COVID-19 correlated with the severity of neutrophilia, thrombocytopenia, depletion of leukocyte (except for neutrophils) and lymphocyte subsets. In comparison to the fatal outcome, survival was associated with higher concentration of C3 and IgM, lower proportion of CD8+CD38+ cells, higher proportion of CD8+NKG2A+ and NK NKG2A+ cells on admission and with the significant increase in the expression on HLA-DR on both CD3+ and CD8+ cells over the first week. Conclusion(s) Our results point out to the dysregulated functional status of depleted CD8+ cells with their over-activation and possibly insufficient compensatory inhibition in COVID-19 non-survivors. Based on our results, the increase in HLA-DR expression on CD3+ and CD8+ cells is necessary for recovery.