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

Abstract

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.

Figure 1

Spatial distribution of Sudan ebolavirus (SUDV) survivors and controls in Uganda. Map illustrating spatial distribution of SUDV survivors (red dots) and controls (green dots) across Mubende, Kassanda, Mityana, Wakiso, and Kampala districts. The study hospitals (blue crosses) include Mubende Regional Referral Hospital, Kikandwa Health Center III in Kassanda, and Entebbe Regional Referral Hospital in Wakiso. The insert map of Uganda showing location of affected districts (orange shading).

Figure 2. Heat map showing symptom reporting among Sudan ebolavirus (SUDV) survivors over 24 months.

This heat map illustrates the proportion of SUDV survivors reporting symptoms across different body systems at 3, 9, 12, 15, and 24 months post-infection. The color gradient represents the symptom reporting rate (%), with red shades indicating higher prevalence (>50%) and green shades representing lower prevalence (<10%).

Figure 3. Duration of Sudan ebolavirus (SUDV) RNA detection in semen and breast milk samples.

This figure illustrates the number of days that semen (orange, n=16) and breast milk (blue, n=4) samples tested positive for SUDV RNA by PCR. Each dot represents an individual participant.