Long-term sequelae in Ebola virus disease survivors receiving anti-Ebola virus therapies in the Democratic Republic of Congo: A prospective cohort study

Background The 2018–2020 Ebola outbreak in the Democratic Republic of Congo (DRC) marked the first major cohort of Ebola survivors treated with advanced therapeutics, including monoclonal antibodies (REGN-EB3, Ansuvimab, ZMapp) and Remdesivir. This study explored factors influencing long-term sequelae in survivors who received these specific therapies. Methods A prospective, multicenter study enrolled 750 Ebola survivors from the tenth outbreak in DRC between April and October 2020. Participants were followed for 12 months to assess the recurrence of clinical sequelae using Weibull and shared frailty models. Results Overall, 650 (86.7%) of 750 of Ebola survivors experienced post-Ebola sequalae. The median age of survivors was 32 years, and 56.7% were female. Among them, 463 (61.7%) experienced neurologic sequelae, 373 (49.7%) musculoskeletal sequelae, and 288 (38.4%) general sequelae. Globally, these persisted for at least 38 months post-discharge, with slight decreases over time. At enrollment (median time to baseline visit, 330 days after discharge), neurologic sequelae were more frequent in the REGN-EB3 group (Hazard Ratio [HR], 2.14; 95% confidence interval [CI] 1.28-3.57) compared to Remdesivir group. Musculoskeletal sequelae were associated with age (1.02 [1.00-1.03]) , with ZMapp treatment (3.17 [1.81-5.56]), and acute-phase hemorrhagic symptoms (1.64 [1.14-2.36]). Ocular sequelae were associated with age (1.04 [1.02-1.06]). Female sex, older age, metabolic comorbidities and REGN-EB3 therapy were associated with recurrent neurologic and musculoskeletal sequelae. Recurrent ocular sequelae were more frequent in adults (1.02 [1.01-1.03]). Conclusions Despite improved survival with monoclonal antibody therapy, our findings highlight a high incidence of neurologic sequelae in the REGN-EB3 group, and musculoskeletal in ZMapp group compared to the Remdesivir group, also among older survivors, women and those with comorbidities. These results underscore the need for targeting long-term care to effectively manage post-Ebola sequelae.