Study Population Characteristics.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19.

鲜有针对急性新型冠状病毒肺炎（Corona Virus Disease 2019, COVID-19）住院患者并发神经系统表现的预后研究，同时采用成人与儿童的多国队列，或是区分中枢神经系统（Central Nervous System, CNS）与外周神经系统（Peripheral Nervous System, PNS）受累情况的研究更是少之又少。本研究依托跨国联邦网络，由各地临床医师与信息学专家对电子健康档案数据进行整理质控，纳入7个国家21个医疗系统的住院新冠患者，评估其住院时长延长与死亡风险。针对成人受试者，本研究采用联邦学习（Federated Learning）方案：在各医疗系统本地运行Cox比例风险模型（Cox Proportional Hazards Model），对聚合结果开展荟萃分析（Meta-Analysis），以估算地理分布异质性人群的不良结局总体风险。由于儿童神经系统受累发生率较低且预后特征特殊，本研究对儿童受试者单独报告描述性统计结果。本研究共纳入2020年1月至2021年10月期间的106229例住院新冠患者，其中≥18岁成人104031例，<18岁儿童2198例；15101例（14%）存在至少1项中枢神经系统诊断，2788例（3%）存在至少1项外周神经系统诊断。在校正人口统计学特征与基础疾病后，与无神经系统受累（No Neurological Condition, NNC）的急性新冠住院患者相比，合并中枢神经系统受累的成人患者住院时长更长（11天 vs 6天），死亡风险更高（风险比=1.78），且死亡发生更早（12天 vs 24天）。合并外周神经系统受累的成人患者住院时长同样长于无神经系统受累组，但死亡风险更低。尽管新冠住院儿童的神经系统受累发生率较低，但合并中枢神经系统受累的儿童死亡比例显著高于无神经系统受累组（6% vs 1%）。总体而言，急性新冠住院期间并发中枢神经系统表现的患者，相较于无神经系统诊断的患者，面临更高的不良临床结局风险。本研究采用的联邦式全球信息学框架（相较于集中式数据收集方案），其应用价值可拓展至新冠疫情之外的临床研究发现领域。