Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
Cell Rep Med. 2021 Mar 16;2(3):100208. doi: 10.1016/j.xcrm.2021.100208. Epub 2021 Feb 5.
SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-infected individuals at acute and/or convalescent time points, up to 102 days after symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18, and IL-10 and broad activation marked by the upregulation of CD38 on innate and adaptive lymphocytes and myeloid cells. Importantly, activated CXCR3cT1 cells in acute COVID-19 significantly correlate with and predict antibody levels and their avidity at convalescence as well as acute neutralization activity. Strikingly, intensive care unit (ICU) patients with severe COVID-19 display higher levels of soluble IL-6, IL-6R, and IL-18, and hyperactivation of innate, adaptive, and myeloid compartments than patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients and integrate key cellular pathways of complex immune networks underpinning severe COVID-19, providing important insights into potential biomarkers and immunotherapies.
SARS-CoV-2 可引起一系列 COVID-19 疾病，但其免疫学基础仍未明确。我们分析了 85 名在急性和/或恢复期感染 SARS-CoV-2 的个体，时间点截至发病后 102 天，共量化了 184 项免疫学参数。急性 COVID-19 表现为高水平的 IL-6、IL-18 和 IL-10，以及先天和适应性淋巴细胞及髓样细胞上 CD38 上调所标志的广泛激活。重要的是，急性 COVID-19 中激活的 CXCR3cT1 细胞与恢复期的抗体水平及其亲和力以及急性中和活性显著相关并具有预测作用。引人注目的是，患有严重 COVID-19 的重症监护病房（ICU）患者比患有中度疾病的患者具有更高水平的可溶性 IL-6、IL-6R 和 IL-18，以及先天、适应性和髓样细胞的过度激活。我们的分析提供了 COVID-19 患者纵向免疫学反应的全面图谱，并整合了严重 COVID-19 所涉及的复杂免疫网络的关键细胞途径，为潜在的生物标志物和免疫疗法提供了重要的见解。
