Neurological diagnoses in hospitalized COVID-19 patients associated with adverse outcomes: A multinational cohort study
Authors: Hutch Meghan R. , Son Jiyeon , Le Trang T. , Hong Chuan , Wang Xuan , Shakeri Hossein Abad Zahra , Morris Michele , Gutiérrez-Sacristán Alba , Klann Jeffrey G. , Spiridou Anastasia , Batugo Ashley , Bellazzi Riccardo , Benoit Vincent , Bonzel Clara-Lea , Bryant William A. , Chiudinelli Lorenzo , Cho Kelly , Das Priyam , González González Tomás , Hanauer David A. , Henderson Darren W. , Ho Yuk-Lam , Loh Ne Hooi Will , Makoudjou Adeline , Makwana Simran , Malovini Alberto , Moal Bertrand , Mowery Danielle L. , Neuraz Antoine , Samayamuthu Malarkodi Jebathilagam , Sanz Vidorreta Fernando J. , Schriver Emily R. , Schubert Petra , Talbert Jeffery , Tan Amelia L. M. , Tan Byorn W. L. , Tan Bryce W. Q. , Tibollo Valentina , Tippman Patric , Verdy Guillaume , Yuan William , Avillach Paul , Gehlenborg Nils , Omenn Gilbert S. ,   The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), Visweswaran Shyam , Cai Tianxi , Luo Yuan , Xia Zongqi 
Published: April 2024

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.