Department of Otolaryngology-Head and Neck Cancer, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Immunology & Immunology and Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.
UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
Immunity. 2022 Jul 12;55(7):1284-1298.e3. doi: 10.1016/j.immuni.2022.06.004. Epub 2022 Jun 7.
While studies have elucidated many pathophysiological elements of COVID-19, little is known about immunological changes during COVID-19 resolution. We analyzed immune cells and phosphorylated signaling states at single-cell resolution from longitudinal blood samples of patients hospitalized with COVID-19, pneumonia and/or sepsis, and healthy individuals by mass cytometry. COVID-19 patients showed distinct immune compositions and an early, coordinated, and elevated immune cell signaling profile associated with early hospital discharge. Intra-patient longitudinal analysis revealed changes in myeloid and T cell frequencies and a reduction in immune cell signaling across cell types that accompanied disease resolution and discharge. These changes, together with increases in regulatory T cells and reduced signaling in basophils, also accompanied recovery from respiratory failure and were associated with better outcomes at time of admission. Therefore, although patients have heterogeneous immunological baselines and highly variable disease courses, a core immunological trajectory exists that defines recovery from severe SARS-CoV-2 infection.
虽然研究已经阐明了 COVID-19 的许多病理生理因素，但对于 COVID-19 缓解期间的免疫变化知之甚少。我们通过质谱细胞术分析了因 COVID-19、肺炎和/或败血症住院的患者以及健康个体的纵向血液样本中的免疫细胞和磷酸化信号状态。COVID-19 患者表现出独特的免疫组成，以及与早期出院相关的早期、协调和升高的免疫细胞信号特征。患者内纵向分析显示，髓样细胞和 T 细胞频率发生变化，细胞类型之间的免疫细胞信号减少，伴随疾病缓解和出院。这些变化伴随着调节性 T 细胞的增加和嗜碱性粒细胞信号的减少，也伴随着呼吸衰竭的恢复，并与入院时的更好结果相关。因此，尽管患者具有异质的免疫基线和高度可变的疾病过程，但存在一个核心免疫轨迹，定义了从严重 SARS-CoV-2 感染中恢复。
