In patients with severe coronavirus disease 2019 (COVID-19), disorders of consciousness (DoC) have emerged as a serious complication. The prognosis and pathophysiology of COVID-DoC remain unclear, complicating decisions about continuing life-sustaining treatment. We describe the natural history of COVID-DoC and investigate its associated brain connectivity profile.

In a prospective longitudinal study, we screened consecutive patients with COVID-19 at our institution. We enrolled critically ill adult patients with a DoC unexplained by sedation or structural brain injury and who were planned to undergo a brain MRI. We performed resting-state fMRI and diffusion MRI to evaluate functional and structural connectivity compared to healthy controls and patients with DoC resulting from severe traumatic brain injury (TBI). We assessed the recovery of consciousness (command following) and functional outcomes (Glasgow Outcome Scale Extended [GOSE] and the Disability Rating Scale [DRS]) at hospital discharge and 3 and 6 months after discharge. We also explored whether clinical variables were associated with recovery from COVID-DoC.

After screening 1,105 patients with COVID-19, we enrolled 12 with COVID-DoC. The median age was 63.5 years (interquartile range 55–76.3 years). After the exclusion of 1 patient who died shortly after enrollment, all of the remaining 11 patients recovered consciousness 0 to 25 days (median 7 [5–14.5] days) after the cessation of continuous IV sedation. At discharge, all surviving patients remained dependent: median GOSE score 3 (1–3) and median DRS score 23 (16–30). Ultimately, however, except for 2 patients with severe polyneuropathy, all returned home with normal cognition and minimal disability: at 3 months, median GOSE score 3 (3–3) and median DRS score 7 (5–13); at 6 months, median GOSE score 4 (4–5), median DRS score 3 (3–5). Ten patients with COVID-DoC underwent advanced neuroimaging; functional and structural brain connectivity in those with COVID-DoC was diminished compared to healthy controls, and structural connectivity was comparable to that in patients with severe TBI.

Patients who survived invariably recovered consciousness after COVID-DoC. Although disability was common after hospitalization, functional status improved over the ensuing months. While future research is necessary, these prospective findings inform the prognosis and pathophysiology of COVID-DoC.

ClinicalTrials.gov identifier: NCT04476589.

在患有严重冠状病毒病 2019 (COVID-19) 的患者中，意识障碍 (DoC) 已成为一种严重的并发症。COVID-DoC 的预后和病理生理学仍不清楚，这使有关继续维持生命治疗的决定变得复杂。我们描述了 COVID-DoC 的自然史，并研究了其相关的大脑连接特征。

在一项前瞻性纵向研究中，我们在我们的机构中​​筛选了连续的 COVID-19 患者。我们招募了患有无法由镇静剂或结构性脑损伤解释的 DoC 并计划接受脑部 MRI 的重症成年患者。我们进行了静息状态 fMRI 和弥散 MRI 以评估与健康对照组和严重创伤性脑损伤 (TBI) 导致的 DoC 患者相比的功能和结构连接性。我们评估了出院时以及出院后 3 个月和 6 个月的意识恢复（命令跟踪）和功能结果（格拉斯哥结果量表扩展 [GOSE] 和残疾评定量表 [DRS]）。我们还探讨了临床变量是否与 COVID-DoC 的恢复有关。

在对 1,105 名 COVID-19 患者进行筛查后，我们招募了 12 名 COVID-DoC 患者。中位年龄为 63.5 岁（四分位距 55-76.3 岁）。在排除 1 名入组后不久死亡的患者后，其余 11 名患者在连续静脉镇静停止后 0 至 25 天（中位时间为 7 [5-14.5] 天）全部恢复意识。出院时，所有幸存的患者仍然依赖：中位 GOSE 评分 3 (1-3) 和中位 DRS 评分 23 (16-30)。然而，最终，除了 2 名患有严重多发性神经病的患者外，所有患者均以正常认知和轻微残疾回家：在 3 个月时，中位 GOSE 评分为 3 (3-3)，中位 DRS 评分为 7 (5-13)；6 个月时，中位 GOSE 评分 4 (4-5)，中位 DRS 评分 3 (3-5)。10 名 COVID-DoC 患者接受了高级神经影像学检查；

幸存下来的患者在 COVID-DoC 后总是恢复意识。虽然住院后残疾很常见，但在接下来的几个月里，功能状态有所改善。虽然未来的研究是必要的，但这些前瞻性研究结果为 COVID-DoC 的预后和病理生理学提供了信息。

ClinicalTrials.gov 标识符：NCT04476589。