Severe long-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection.

Background: While long-term clinical sequelae following ebolavirus disease (EVD) due to Zaire ebolavirus (EBOV) strain has been characterized, this has not been explored for Sudan ebolavirus (SUDV) strain. Methods: We enrolled 87 SUDV survivors from the 2022-2023 outbreak in Uganda, alongside 176 age-, sex-, and location-matched controls. Clinical symptom data were collected at 3-, 9-, 12-, 15-, and 18-and 24-months post-infection. Serum, semen, and breast milk samples were collected and tested for viral RNA. Results: Of 86 SUDV survivors, 57.5% reported significantly higher frequencies of clinical symptoms involving musculoskeletal (45.0%, P < 0.001), central nervous system (36.3%, p < 0.001), ophthalmologic (20%, P < 0.001), and respiratory (10%, P < 0.001) systems than those observed among controls. The risk ratio of occurrence was highest for ophthalmologic (20% vs 3.4%, RR = 5.9; p < 0.001) and central nervous systems symptoms (36.3% vs 6.8%, RR = 5.3, p < 0.001), and lowest for reproductive system (13.8% vs 8.5%; RR = 1.6; p > 0.005). Importantly, 50% of SUDV survivors reported persistent multi-systemic symptoms, including low back pain, hand and feet numbness, confusion, and diarrhoea that resulted in inability to perform basic activities of living. Viral RNA was detected in semen for a median duration of 131 days (range: 111-210 days) and in breast milk for a median of 149 days (range: 111-199 days). Conclusions: This study demonstrates that SUDV survivors develop long-term clinical sequelae characterized by persistent multi-systemic clinical symptoms. Detection of viral RNA in semen and breastmilk for up to 7 months post-infection suggest prolonged persistence, with the possibility of latency and reactivation of the virus.