Background Knowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses. Methods This was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU). Mononuclear cells were purified from bronchoalveolar lavage fluid (BALF) and blood, and analysed by spectral flow cytometry; inflammatory mediators were measured in BALF and plasma. Findings Paired blood and BALF samples were obtained from 17 patients, four of whom died in the ICU. Macrophages and T cells were the most abundant cells in BALF, with a high percentage of T cells expressing the ƴδ T cell receptor. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells (87·3% and 83·8%, respectively), and these cells expressed higher levels of the exhaustion marker programmad death-1 than in peripheral blood. Prolonged ICU stay (>14 days) was associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma. Interpretation The bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood. Fully elucidating COVID-19 pathophysiology will require investigation of the pulmonary immune response. The data that support the findings of this study are available from the corresponding author, AS, upon reasonable request.

中文翻译：

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COVID-19 重症患者气道和血液中不同的细胞免疫特征

COVID-19 病理生理学的背景知识几乎完全来自检查血液免疫反应的研究。我们在这里旨在分析严重 COVID-19 期间的肺免疫反应，并将其与血液反应进行比较。方法 这是一项针对入住重症监护室 (ICU) 的 COVID-19 患者的观察性研究。从支气管肺泡灌洗液（BALF）和血液中纯化单核细胞，并通过光谱流式细胞术进行分析；在 BALF 和血浆中测量炎症介质。结果 从 17 名患者中获得配对的血液和 BALF 样本，其中 4 人在 ICU 中死亡。巨噬细胞和 T 细胞是 BALF 中最丰富的细胞，其中表达 ƴδ T 细胞受体的 T 细胞比例很高。在肺部，CD4 和 CD8 T 细胞主要是效应记忆细胞（分别为 87·3% 和 83·8%），并且这些细胞表达的耗竭标记程序性死亡-1 水平高于外周血。ICU 住院时间延长（> 14 天）与外周血中活化 T 细胞比例降低有关，在 BALF 中更是如此。在致命的 COVID-19 病例中，血液中的 T 细胞活化较高，但在 BALF 中没有。与血浆相比，BALF 中炎症介质水平的升高更为明显。解释 COVID-19 中的支气管肺泡免疫反应具有独特的局部特征，与外周血中的免疫特征截然不同。充分阐明 COVID-19 的病理生理学需要研究肺免疫反应。