The absolute counts of CD3+CD4+CD45+ lymphocytes, CD3+CD8+CD45+ lymphocytes, CD3−CD16+CD56+CD45+ cells, and CD19+CD45+ lymphocytes were lower among patients with COVID-19 compared with those in 10 healthy subjects adjusted for age and gender. Compared with patients with CAP caused by 2009H1N1, patients with COVID-19 had lower CD3+CD4+CD45+ lymphocytes but higher CD3+CD16+CD45+ cells and CD19+CD45+ lymphocytes (Figures 2A–2E). Those patients with immune dysregulation caused by COVID-19 had lower counts of CD3+ CD4+ CD45+ lymphocytes, CD3+CD8+CD45+ lymphocytes, and CD3−CD16+CD56+CD45+ cells than those at an intermediate immune state. When comparisons were limited to patients with SRF and infection by one of the two viruses, it was found that infection by SARS-CoV-2 was accompanied by lower CD3+CD4+CD45+ lymphocytes but with higher CD3−CD16+CD56+CD45+ cells and CD19+CD45+ lymphocytes than 2009H1N1 (Figures 2F–2J). The Th17 function as assessed by IL-17 production capacity was downregulated among patients with immune dysregulation (Figure 2K).
Figure 2 CD4 Cell and NK Cell Cytopenias Are Characteristics of Infection by SARS-CoV-2
(A–E) Absolute counts of CD3+CD4+CD45+ lymphocytes (A), CD3+CD8+CD45+ lymphocytes (B), CD3+CD16+CD56+CD45+ lymphocytes (C), CD3−CD16+CD56+CD45+ cells (D), and CD19+CD45+ lymphocytes (E) among healthy volunteers, patients with CAP caused by the 2009H1N1 influenza virus, and patients with CAP caused by COVID-19. Patients with COVID-19 are classified into three states of immune activation: intermediate, dysregulation, and MAS.
(F–J) absolute counts of CD3+CD4+CD45+ lymphocytes (F), CD3+CD8+CD45+ lymphocytes (G), CD3+CD16+CD56+CD45+ lymphocytes (H), CD3−CD16+CD56+CD45+ cells (I), and CD19+CD45+ lymphocytes (J) among patients with severe respiratory failure developing in the field of CAP caused by the 2009H1N1 influenza virus and COVID-19.
(K) IL-17 production by PBMCs after stimulation with heat-killed Candida albicans.
Bars in each graphic represent mean values and standard errors. Statistical comparisons are indicated by the arrows; ns: non-significant; ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001. Comparisons were done by the Mann-Whitney U test followed by correction for multiple comparisons.