COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian patients hospitalized with COVID-19. We identified core clinical and peripheral blood signatures differentiating disease progression between patients who recovered from severe disease compared with those who succumbed to the disease. Signatures were heterogeneous among fatal cases yet clustered into two patient groups: “early death” (<15 days until death) and “late death” (>15 days). Progression to early death was characterized systemically and in lung histopathological samples by rapid endothelial and myeloid activation and the presence of thrombi associated with SARS-CoV-2 + macrophages. In contrast, progression to late death was associated with fibrosis, apoptosis, and SARS-CoV-2 + epithelial cells in postmortem lung tissue. In late death cases, cytotoxicity, interferon, and T helper 17 (T H 17) signatures were only detectable in the peripheral blood after 2 weeks of hospitalization. Progression to recovery was associated with higher lymphocyte counts, T H 2 responses, and anti-inflammatory–mediated responses. By integrating antemortem longitudinal blood signatures and spatial single-cell lung signatures from postmortem lung samples, we defined clinical parameters that could be used to help predict COVID-19 outcomes.

中文翻译：

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空间分辨的单细胞肺图谱与临床和血液特征相结合，可区分 COVID-19 疾病轨迹


COVID-19 的特点是症状和疾病轨迹范围广泛。了解急性 COVID-19 期间临床生物标志物与肺部病理学之间的相关性对于了解其多样化的发病机制并为更有效的治疗提供信息是必要的。在这里，我们对 142 名因 COVID-19 住院的巴西患者的纵向临床参数、外周血标志物和肺部病理进行了综合分析。我们确定了区分重症康复患者与死于疾病的患者之间疾病进展的核心临床和外周血特征。死亡病例的特征存在异质性，但分为两组：“早死”（x3C15 天至死亡）和“晚期死亡”（x3E15 天）。在全身和肺组织病理学样本中，通过快速内皮细胞和骨髓激活以及与 SARS-CoV-2 + 巨噬细胞相关的血栓的存在来表征进展为早期死亡。相比之下，进展为晚期死亡与死后肺组织中的纤维化、细胞凋亡和 SARS-CoV-2 + 上皮细胞有关。在晚期死亡病例中，细胞毒性、干扰素和辅助性 T 细胞 17 （T H 17） 特征仅在住院 2 周后才能在外周血中检测到。进展至恢复与较高的淋巴细胞计数、T H 2 反应和抗炎介导的反应相关。通过整合死前纵向血液特征和死后肺样本的空间单细胞肺特征，我们定义了可用于帮助预测 COVID-19 结果的临床参数。