Klein Jonathan, Brito Anderson F, Trubin Paul, Lu Peiwen, Wong Patrick, Alpert Tara, Peña-Hernández Mario A, Haynes Winston, Kamath Kathy, Liu Feimei, Vogels Chantal B F, Fauver Joseph R, Lucas Carolina, Oh Jieun, Mao Tianyang, Silva Julio, Wyllie Anne L, Muenker M Catherine, Casanovas-Massana Arnau, Moore Adam J, Petrone Mary E, Kalinich Chaney C, Cruz Charles Dela, Farhadian Shelli, Ring Aaron, Shon John, Ko Albert I, Grubaugh Nathan D, Israelow Benjamin, Iwasaki Akiko, Azar Marwan M
medRxiv. 2021 Mar 26:2021.03.24.21253992. doi: 10.1101/2021.03.24.21253992.
Prior to the emergence of antigenically distinct SARS-CoV-2 variants, reinfections were reported infrequently - presumably due to the generation of durable and protective immune responses. However, case reports also suggested that rare, repeated infections may occur as soon as 48 days following initial disease onset. 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 - confirmed by whole virus genome sequencing - 7 months after primary infection. To elucidate the immunological mechanisms responsible for SARS-CoV-2 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. The patient's immune system was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we also identified the development of neutralizing antibodies and the formation of 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 in this patient. In summary, our study suggests that a low neutralizing antibody presence alone is not sufficient to confer resistance against reinfection. Thus, patients with solid organ transplantation, or patients who are otherwise immunosuppressed, who recover from infection with SARS-CoV-2 may not develop sufficient protective immunity and are at risk of reinfection.
在抗原性不同的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体出现之前，再次感染的报告很少——可能是由于产生了持久的保护性免疫反应。然而，病例报告也表明，在初次发病后48天就可能发生罕见的反复感染。目前尚不清楚导致SARS-CoV-2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，在初次感染7个月后出现了有症状的SARS-CoV-2反复感染，这通过全病毒基因组测序得以证实。为了阐明导致SARS-CoV-2再次感染的免疫机制，我们在初次和反复感染SARS-CoV-2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反应是短暂的、质量较差的适应性免疫反应。在再次感染之前，针对肾移植急性排斥反应的干预治疗进一步损害了患者的免疫系统。重要的是，我们还确定了在SARS-CoV-2再次感染之前中和抗体的产生以及体液记忆反应的形成。然而，这些中和抗体未能提供针对再次感染的保护，这表明有效预防SARS-CoV-2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，这表明该患者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。总之，我们的研究表明，仅存在低水平的中和抗体不足以赋予抵抗再次感染的能力。因此，实体器官移植患者或其他免疫抑制患者在从SARS-CoV-2感染中康复后可能无法产生足够的保护性免疫，并有再次感染的风险。
