Dysregulation of the immune response affects the outcome of critical COVID-19 patients

Abstract

Critical cases of coronavirus disease 2019 (COVID-19) are associated with a high risk of mortality. It remains unclear why patients with the same critical condition have different outcomes. We aimed to explore relevant factors that may affect the prognosis of critical COVID-19 patients. Six critical COVID-19 inpatients were included in our study. The six patients were divided into two groups based on whether they had a good or poor prognosis. We collected peripheral blood samples at admission and the time point of exacerbation to compare differences in the phenotypes and functions of major populations of immune cells between the groups. On admission, compared to patients with poor prognoses, those with good prognoses had significantly higher counts of monocytes (P < .05), macrophages (P < .05), higher frequency of CD3⁺ CD4⁺ CD45RO⁺ CXCR3⁺ subsets (P < .05), higher frequency of CD14⁺ CD11C⁺ HLA-DR⁺ subset of dendritic cells (P < .05), and a lower count of neutrophils (P < .05). At the time point of exacerbation, the proportions of naïve CD4⁺ T cells (P < .05), Tregs, and Th2 cells in the poor prognosis group were relatively higher than those in the good prognosis group, and CD4⁺ memory T cells were relatively lower (P < .05). According to our results, the poor prognosis group showed a worse immune response than the good prognosis group at the time of admission and at exacerbation. Dysregulation of the immune response affects the outcome of critical COVID-19 patients.

Keywords: COVID-19; dendritic cells; immune response; lymphocyte subsets; outcome.

Figure 1

CyTOF‐based analysis revealed immune cell signatures in the peripheral blood of COVID‐19 patients. A, Subsets of blood cells revealed by CyTOF are indicated, and relative marker expression is also displayed. B, The proportion of immune cell subpopulations is displayed in a heat map using the mean value of each group in min/max form (left). Comparisons of peripheral blood immune cell subsets among groups are displayed in a heat map using Minus log 10 (P value) (right). COVID‐19, coronavirus disease 2019

Figure 2

In‐depth phenotyping of immune cells by PhenoGraph. A, The viSNE plot of each group is shown as colored by cluster. B, Normalized marker expression of identified clusters in the heatmap. C, Heatmap of all cluster abundances among groups. D, Protein (active markers, chemokine receptors) expression of metacluster2 (DCs) and 25 (monocytes) are displayed