Section Paediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center.
Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, The Netherlands.
Curr Opin Infect Dis. 2021 Jun 1;34(3):181-186. doi: 10.1097/QCO.0000000000000724.
Despite its crucial role in protection against viral infections, mucosal immunity has been largely understudied in the context of coronavirus disease 2019 (COVID-19). This review outlines the current evidence about the role of mucosal immune responses in the clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as potential mucosal mechanisms of protection against (re-)infection.
The angiotensin-converting enzyme 2 cellular entry receptor for SARS-CoV-2 is most highly expressed in the upper respiratory tract and most SARS-CoV-2 shedding occurs from the upper respiratory tract. Viral shedding peaks early during infection around the onset of symptoms, before dropping rapidly in most individuals within 7 days of symptom onset, suggesting mucosal inhibition of viral infection. Serum and mucosal immunoglobulin G and immunoglobulin M responses were found to be strongly correlated in infected patients, whereas correlations were much weaker for immunoglobulin A (IgA). Mucosal IgA responses have been detected in infected cases in the absence of serum antibody responses, with mucosal antibody levels correlating strongly with virus neutralization. Bulk and single-cell RNA sequencing analysis of nasopharyngeal swabs and bronchoalveolar lavage samples of COVID-19 patients revealed the induction of mucosal chemokine and cytokine genes, complement pathways, Janus Kinase/Signal Transducer and Activator of Transcription signaling and cytotoxic T cells.
Although most clinical studies focus on antibodies and cellular immunity in peripheral blood, mucosal immune responses in the respiratory tract play a key role in the early restriction of viral replication and the clearance of SARS-CoV-2. Identification of mucosal biomarkers associated with viral clearance will allow monitoring of infection-induced immunity. Further studies are needed to understand how the systemic immunological endpoints measured in vaccination studies translate to mucosal protection against SARS-CoV-2 infection.
目的综述：尽管黏膜免疫在抵抗病毒感染方面起着至关重要的作用，但在 2019 年冠状病毒病（COVID-19）的背景下，对黏膜免疫的研究还很不充分。本文概述了目前关于黏膜免疫反应在清除严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染方面的作用的证据，以及针对（再次）感染的潜在黏膜保护机制。
最新发现：SARS-CoV-2 的血管紧张素转换酶 2 细胞进入受体在上呼吸道表达水平最高，且大多数 SARS-CoV-2 脱落发生在上呼吸道。病毒脱落最早在感染早期出现，症状出现时达到峰值，然后在大多数个体中迅速下降，在症状出现后 7 天内下降，这表明黏膜抑制了病毒感染。在感染患者中，血清和黏膜免疫球蛋白 G 和免疫球蛋白 M 反应之间呈强烈相关性，而免疫球蛋白 A（IgA）之间的相关性较弱。在感染病例中检测到黏膜 IgA 反应，而血清抗体反应缺失，黏膜抗体水平与病毒中和呈强相关性。对 COVID-19 患者鼻咽拭子和支气管肺泡灌洗液样本的批量和单细胞 RNA 测序分析显示，诱导了黏膜趋化因子和细胞因子基因、补体途径、Janus 激酶/信号转导和转录激活因子信号和细胞毒性 T 细胞。
总结：尽管大多数临床研究集中在血清抗体和细胞免疫上，但呼吸道黏膜免疫反应在早期限制病毒复制和清除 SARS-CoV-2 方面发挥着关键作用。鉴定与病毒清除相关的黏膜生物标志物将有助于监测感染诱导的免疫。需要进一步研究来了解疫苗研究中测量的系统免疫学终点如何转化为针对 SARS-CoV-2 感染的黏膜保护。
