Laboratory of Immunology and Cellular Stress, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Laboratory of Cancer Immunoregulation, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Front Immunol. 2021 Oct 21;12:769059. doi: 10.3389/fimmu.2021.769059. eCollection 2021.
The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.
严重 COVID-19 患者的预后促使研究人员在区域层面上揭示 SARS-CoV-2 发病机制的机制。在这项工作中，我们旨在了解不同疾病严重程度的严重 COVID-19 患者以及长期康复后的免疫动力学。我们分析了 66 名入住智利大学临床医院的 COVID-19 患者的免疫细胞亚群和 SARS-CoV-2 特异性抗体同种型，这些患者根据世界卫生组织的十点临床进展评分进行了分类。其中包括 29 名中度患者（评分 4-5）和 37 名严重患者，其中 18 名患者接受高流量鼻导管吸氧（评分 6），19 名患者接受有创机械通气（评分 7-9），以及 28 名恢复期患者和 28 名健康对照者。此外，六名从疾病中康复的严重患者在 300 多天内进行了纵向随访。我们的数据表明，与中度和恢复期患者相比，严重 COVID-19 患者显示出更高频率的浆母细胞、活化的 T 细胞和 SARS-CoV-2 特异性抗体。值得注意的是，在严重 COVID-19 组中，迅速进展为有创机械通气的患者显示出更高频率的浆母细胞、单核细胞、嗜酸性粒细胞、Th1 细胞和 SARS-CoV-2 特异性 IgG，而高流量鼻导管吸氧的患者则不然。这些发现表明，进展为有创机械通气的严重 COVID-19 患者表现出独特的免疫类型。此外，从严重 COVID-19 中康复的患者在出院后 100 天开始恢复正常比例的免疫细胞，并在整个研究过程中保持高水平的 SARS-CoV-2 特异性 IgG，这是免疫记忆的一个指示性标志。因此，这项工作可以为更好地理解严重 COVID-19 发病机制的不同结果提供有用的信息。
