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苏丹埃博拉病毒病幸存者感染两年后的严重长期临床后遗症

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

作者信息

Muwonge Haruna, Nasimiyu Carolyne, Bakamutumaho Barnabas, Elyanu Peter, Joloba Moses L, Situma Silvia, Schieffelin John, Gunn Bronwyn, Bai Shuangyi, Breiman Robert F, Ssewanyana Isaac, Nabadda Susan, Lutwama Julius, Tegen Yonas, Muruta Allan, Kirenga Bruce, Olaro Charles, Aceng Jane Ruth, Bosa Henry Kyobe, Njenga M Kariuki

机构信息

Makerere University Medical School.

Washington State University Global Health-Kenya.

出版信息

Res Sq. 2025 Apr 17:rs.3.rs-6325522. doi: 10.21203/rs.3.rs-6325522/v1.

DOI:10.21203/rs.3.rs-6325522/v1
PMID:40321748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12047994/
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.

摘要

背景

虽然已对扎伊尔埃博拉病毒(EBOV)毒株所致埃博拉病毒病(EVD)的长期临床后遗症进行了特征描述,但尚未对苏丹埃博拉病毒(SUDV)毒株的此类情况进行研究。

方法

我们招募了87名来自2022 - 2023年乌干达疫情的SUDV幸存者,以及176名年龄、性别和地点匹配的对照者。在感染后的3、9、12、15、18和24个月收集临床症状数据。采集血清、精液和母乳样本并检测病毒RNA。

结果

在86名SUDV幸存者中,57.5%报告称涉及肌肉骨骼系统(45.0%,P < 0.001)、中枢神经系统(36.3%,P < 0.001)、眼科(20%,P < 0.001)和呼吸系统(10%,P < 0.001)的临床症状出现频率显著高于对照组。眼科症状(20%对3.4%,RR = 5.9;P < 0.001)和中枢神经系统症状(36.3%对6.8%,RR = 5.3,P < 0.001)的发生风险比最高,生殖系统症状的发生风险比最低(13.8%对8.5%;RR = 1.6;P > 0.005)。重要的是,50%的SUDV幸存者报告有持续的多系统症状,包括腰痛、手脚麻木、意识模糊和腹泻,导致无法进行基本生活活动。精液中检测到病毒RNA的中位持续时间为131天(范围:111 - 210天),母乳中为149天(范围:111 - 199天)。

结论

本研究表明,SUDV幸存者会出现以持续的多系统临床症状为特征的长期临床后遗症。感染后长达7个月在精液和母乳中检测到病毒RNA,提示病毒持续存在时间延长,存在潜伏和重新激活的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5f/12047994/3fef8e5049bb/nihpp-rs6325522v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5f/12047994/8eb25ab23d39/nihpp-rs6325522v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5f/12047994/e0498da8b056/nihpp-rs6325522v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5f/12047994/3fef8e5049bb/nihpp-rs6325522v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5f/12047994/8eb25ab23d39/nihpp-rs6325522v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5f/12047994/e0498da8b056/nihpp-rs6325522v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5f/12047994/3fef8e5049bb/nihpp-rs6325522v1-f0003.jpg

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Prevalence of somatic symptoms among Ebola Virus Disease (EVD) survivors in Africa: a systematic review and meta-analysis.非洲埃博拉病毒病(EVD)幸存者躯体症状的流行情况:系统评价和荟萃分析。
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Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunity.
埃博拉病毒将 IRF3 隔离在病毒包含体中,以逃避宿主抗病毒免疫。
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