The Dynamic Immunological Parameter Landscape in Coronavirus Disease 2019 Patients With Different Outcomes

Abstract

Objectives: The longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported.

Methods: Parameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset.

Results: This study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients. Generally, deceased patients demonstrated a gradual increase of neutrophils and IL-6 but a decrease of lymphocytes and platelets after the onset of illness. Specifically, sustained low numbers of CD8⁺ T cells, NK cells, and dendritic cells were noted in deceased patients, while these cells gradually restored in mild and severe patients. Furthermore, deceased patients displayed a rapid increase of HLA-DR expression on CD4⁺ T cells in the early phase, but with a low level of overall CD45RO and HLA-DR expressions on CD4⁺ and CD8⁺ T cells, respectively. Notably, in the early phase, deceased patients showed a lower level of plasma cells and antigen-specific IgG, but higher expansion of CD16⁺CD14⁺ proinflammatory monocytes and HLA-DR^-CD14⁺ monocytic-myeloid-derived suppressor cells (M-MDSCs) than mild or severe patients. Among these immunological parameters, M-MDSCs showed the best performance in predicting COVID-19 mortality, when using a cutoff value of ≥10%. Cluster analysis found a typical immunological pattern in deceased patients on day 9 after onset, which was characterized as the increase of inflammatory markers (M-MDSCs, neutrophils, CD16⁺CD14⁺ monocytes, and IL-6) but a decrease of host immunity markers.

Conclusions: This study systemically characterizes the kinetics of immunity of COVID-19, highlighting the importance of immunity in patient prognosis.

Keywords: COVID-19; adaptive immunity; humoral immunity; innate immunity; outcome.