SARS-CoV-2 is associated with a 3.4% mortality rate in patients with severe disease. The pathogenesis of severe cases remains unknown. We performed an in-depth prospective analysis of immune and inflammation markers in two patients with severe COVID-19 disease from presentation to convalescence. Peripheral blood from 18 SARS-CoV-2-infected patients, 9 with severe and 9 with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells (MDSCs) and cytokine profiles. MDSC functionality was tested in vitro. In four severe and in four mild patients, a longitudinal analysis was performed daily from the day of admission to the early convalescent phase. Early after admission severe patients showed neutrophilia, lymphopenia, increase in effector T cells, a persisting higher expression of CD95 on T cells, higher serum concentration of IL-6 and TGF-β, and a cytotoxic profile of NK and T cells compared with mild patients, suggesting a highly engaged immune response. Massive expansion of MDSCs was observed, up to 90% of total circulating mononuclear cells in patients with severe disease, and up to 25% in the patients with mild disease; the frequency decreasing with recovery. MDSCs suppressed T-cell functions, dampening excessive immune response. MDSCs decline at convalescent phase was associated to a reduction in TGF-β and to an increase of inflammatory cytokines in plasma samples. Substantial expansion of suppressor cells is seen in patients with severe COVID-19. Further studies are required to define their roles in reducing the excessive activation/inflammation, protection, influencing disease progression, potential to serve as biomarkers of disease severity, and new targets for immune and host-directed therapeutic approaches.

严重疾病患者的SARS-CoV-2死亡率为3.4％。严重病例的发病机制仍然未知。我们对两名重度COVID-19疾病从表现到康复的患者进行了免疫和炎症标志物的深入前瞻性分析。入院时从18例SARS-CoV-2感染患者中抽取外周血，其中9例患有严重，9例患有轻度COVID-19疾病，并分析T细胞活化特性，髓样抑制细胞（MDSC）和细胞因子特性。MDSC功能已在体外测试。从入院当天至早期恢复期，每天对四名重症患者和四名轻度患者进行纵向分析。入院后早期，严重患者表现为中性粒细胞增多，淋巴细胞减少，效应T细胞增加，与轻度患者相比，CD95在T细胞上持续更高的表达，更高的IL-6和TGF-β血清浓度以及NK和T细胞的细胞毒性特征，表明免疫反应高度活跃。观察到MDSCs的大规模扩增，在严重疾病患者中高达总循环单核细胞的90％，在轻度疾病患者中高达25％；频率随着恢复而降低。MDSCs抑制T细胞功能，抑制过度的免疫反应。恢复期的MDSCs下降与血浆样品中TGF-β的降低和炎性细胞因子的增加有关。在严重COVID-19的患者中可以看到抑制细胞的大量扩增。需要进一步研究以确定它们在减少过度激活/发炎，保护，