It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60–63] years vs 64 [62–66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6–9.0] vs 5.8 [5.3–6.4], p < 0.001) and increased, while more female patients (26 [23–29]% vs 41 [35–48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2–7.2| days vs 9.7 [8.9–10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123–141] mmHg vs 101 [91–113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20–48] mmHg vs 70 [41–100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4–7]% vs 20 [14–29], p < 0.001) and non-invasive mechanical ventilation (14 [11–18]% vs 24 [17–33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76–86]% vs 74 [64–82]%, p < 0.001). The ICU mortality (23 [19–26]% vs 17 [12–25]%, p < 0.001) and length of stay (14 [13–16] days vs 11 [10–13] days, p < 0.001) decreased over 19 months of the pandemic. Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

中文翻译：

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大流行期间危重 COVID-19 患者的疾病特征动态和临床管理：对前瞻性、国际、多中心 RISC-19-ICU 登记的分析

在大流行期间，全球重症监护病房 (ICU) 收治的 COVID-19 重症患者的特征、病程、临床管理和结果如何变化仍然难以捉摸。由全球 22 个国家的 90 个 ICU 组成的前瞻性观察性登记，包括经实验室确认的 COVID-19 危重表现需要高级器官支持的患者。采用考虑医院和国家可变性的分层、广义线性混合效应模型来分析所研究变量在大流行期间的持续演变。从 2020 年 3 月到 2021 年 9 月，共纳入 4041 名患者。在此期间，入院患者的年龄（62 [95% CI 60-63] 岁 vs 64 [62-66] 岁，p < 0. 001）和 ICU 入院时器官功能障碍的严重程度降低（序贯器官衰竭评估 8.2 [7.6-9.0] vs 5.8 [5.3-6.4]，p < 0.001）并增加，而更多女性患者（26 [23-29]% vs 41 [35–48]%, p < 0.001) 被录取。在大流行后期，症状出现和住院以及入住 ICU 之间的时间跨度变得更长（6.7 [6.2-7.2| 天 vs 9.7 [8.9-10.5] 天，p < 0.001）。入院时的 PaO2/FiO2 较低（132 [123–141] mmHg vs 101 [91–113] mmHg，p < 0.001），但与 2020 年初相比，在 2021 年底入住 ICU 的最初 5 天中显示出更快的改善（34 [20–48] mmHg 与 70 [41–100] mmHg，p = 0.05）。接受类固醇和托珠单抗治疗的患者数量增加，而在大流行过程中，治疗性抗凝剂的使用呈现出倒 U 形的行为。接受高流量氧气治疗的患者比例（5 [4-7]% vs 20 [14-29]，p < 0.001）和无创机械通气（14 [11-18]% vs 24 [17-33] ]%，p < 0.001）在整个大流行期间随着有创机械通气的减少而增加（82 [76-86]% 对 74 [64-82]%，p < 0.001）。ICU 死亡率（23 [19-26]% vs 17 [12-25]%，p < 0.001）和住院时间（14 [13-16] 天 vs 11 [10-13] 天，p < 0.001）下降超过 19 个月的大流行病。危重 COVID-19 患者的特征和病程随着临床管理不断演变，在整个大流行期间导致更年轻、