Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.

自主神经功能障碍对急性 COVID-19 的严重程度以及从 COVID-19（长期 COVID）恢复后的症状负担产生了重大影响，但根本原因仍不清楚。在这里，我们假设迷走神经在 COVID-19 中受到影响，这可能会导致自主神经功能障碍。我们对 COVID-19 患者和对照组的死后迷走神经进行了组织病理学表征，并检测了 SARS-CoV-2 RNA 以及主要由单核细胞组成的炎症细胞浸润。此外，我们进行了 RNA 测序，结果显示神经元、内皮细胞和雪旺细胞有强烈的炎症反应，这与 SARS-CoV-2 RNA 负载相关。最后，我们筛查了 323 名患者的临床队列，以检测迷走神经感染的临床表型，发现危重 COVID-19 的非幸存者中呼吸频率降低。我们的数据表明，SARS-CoV-2 会诱发迷走神经炎症，随后导致自主神经功能障碍，从而导致严重的疾病进程，并可能导致长期新冠病毒中观察到的自主神经功能障碍。