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实体器官移植受者中新冠病毒再次感染的纵向免疫分析

Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient.

作者信息

Klein Jon, Brito Anderson, Trubin Paul, Lu Peiwen, Wong Patrick, Alpert Tara, Pena-Hernandez Mario, Haynes Winston, Kamath Kathy, Liu Feimei, Vogels Chantal, Fauver Joseph, Lucas Carolina, Oh Ji Eun, Mao Tianyang, Silva Julio, Wyllie Anne, Muenker M Catherine, Casanovas-Massana Arnau, Moore Adam, Petrone Mary, Kalinich Chaney, Cruz Charles Dela, Farhadian Shelli, Ring Aaron, Shon John, Ko Albert, Grubaugh Nathan, Goldman-Israelow Benjamin, Iwasaki Akiko, Azar Marwan

机构信息

Yale University.

Yale.

出版信息

Res Sq. 2021 May 5:rs.3.rs-405958. doi: 10.21203/rs.3.rs-405958/v1.

Abstract

The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal-transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection 7 months after primary infection. To elucidate the immunological mechanisms responsible for reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses that was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we identified the development of neutralizing antibodies and humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation.

摘要

目前尚不清楚导致新冠病毒再次感染的潜在免疫缺陷。在此,我们描述了一名肾移植受者,其在初次感染7个月后出现了复发性、有症状的新冠病毒感染。为了阐明导致再次感染的免疫机制,我们在初次和复发性新冠病毒感染期间对细胞和体液反应进行了纵向分析。我们发现,该患者对初次感染的适应性免疫反应短暂且质量不佳,并且在再次感染前因肾移植急性排斥反应的介入治疗而进一步受损。重要的是,我们在新冠病毒再次感染之前就发现了中和抗体和体液记忆反应的产生。然而,这些中和抗体未能提供针对再次感染的保护作用,这表明有效预防新冠病毒再次感染还需要其他因素。此外,我们没有发现支持病毒逃避初次适应性免疫反应的证据,这表明再次感染的易感性可能由宿主因素而非病原体适应性决定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7dc/8132249/34cafd361e90/nihpp-rs405958v1-f0001.jpg

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