An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019

Abstract

Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.

Keywords: COVID-19; MDSC; NK cells; cytotoxic cells; inflammation.

Figure 1.

A, Data are reported as median and interquartile range for immunological subset frequency, inflammatory cytokines, and cytotoxic cell percentage. Statistical differences were assessed by Mann-Whitney test. *P < .05; ***P < .001; ****P < .0001. B, Principal component analysis of the immunological parameters of patients with coronavirus disease 2019 (COVID-19) patients. Graph of variables: directions and magnitude of each vector indicate the contribution of the corresponding mediator levels to principal component 1 and principal component 2. Different colors represent different correlation groups between mediator levels and principal components. C, Immunological correlations among inflammatory and immunological variables (innate, adaptive, and cytotoxic cells). The nonparametric Spearman test was applied to evaluate multiple correlations. A color map matrix (left panel) shows the strength and direction of these correlations (−0.5 [green] to +1 [red]). Statistically significant correlations (P < .05) between variables are shown in the right panel. Variables 1 indicate the parameters shown on the x-axis; variables 2 indicate the parameters shown on the y-axis. D, Frequency of perforin-expressing natural killer cells in non–intensive care unit (ICU) patients, in ICU patients, and in healthy donors. Statistical differences were assessed by Mann-Whitney test. Abbreviations: HD, healthy donors; ICU, intensive care unit; IL, interleukin; IQR, interquartile range; MSDC, myeloid-derived suppressor cells; NK, natural killer; ns, not significant; PCA, principal component analysis; Perf⁺, perforin-expressing; TNF-α, tumor necrosis factor alpha.