Barzaghi Federica, Visconti Camilla, Pipitone Giovanni Battista, Bondesan Simone, Molli Giulia, Giannelli Stefania, Sartirana Claudia, Lampasona Vito, Bazzigaluppi Elena, Brigatti Cristina, Gervais Adrian, Bastard Paul, Tassan Din Chiara, Molinari Chiara, Piemonti Lorenzo, Casanova Jean-Laurent, Carrera Paola, Casari Giorgio, Aiuti Alessandro
Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Infect Dis. 2025 Feb 4;231(1):e206-e212. doi: 10.1093/infdis/jiae321.
Patients with severe West Nile virus and SARS-CoV-2 infections deserve accurate diagnosis of underlying diseases, determining possible anti-interferon autoantibody production, since they must receive antiviral and immunological therapies to enhance antiviral response. The current study aimed to investigate determinants of severity in a previously healthy patient who experienced 2 life-threatening infections, from West Nile Virus (WNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). During coronavirus disease 2019 (COVID-19) hospitalization he was diagnosed with a thymoma, retrospectively identified as already present at the time of WNV infection. Heterozygosity for p.Pro554Ser in the TLR3 gene, which increases susceptibility to severe COVID-19, and homozygosity for CCR5 c.554_585del, associated with severe WNV infection, were found. Neutralizing anti-interferon (IFN)-α and anti-IFN-ω autoantibodies were detected, likely induced by the underlying thymoma and increasing susceptibility to both severe COVID-19 pneumonia and West Nile encephalitis.
患有严重西尼罗河病毒和SARS-CoV-2感染的患者需要准确诊断潜在疾病,确定是否可能产生抗干扰素自身抗体,因为他们必须接受抗病毒和免疫治疗以增强抗病毒反应。本研究旨在调查一名既往健康的患者发生两种危及生命感染(西尼罗河病毒[WNV]和严重急性呼吸综合征冠状病毒2[SARS-CoV2])的严重程度的决定因素。在2019冠状病毒病(COVID-19)住院期间,他被诊断出患有胸腺瘤,回顾性分析发现该胸腺瘤在WNV感染时就已存在。研究发现,TLR3基因中p.Pro554Ser杂合性增加了对严重COVID-19的易感性,而CCR5 c.554_585del纯合性与严重WNV感染相关。检测到中和性抗干扰素(IFN)-α和抗IFN-ω自身抗体,可能是由潜在的胸腺瘤诱导产生的,增加了对严重COVID-19肺炎和西尼罗河脑炎的易感性。