Janeri Fröberg1,2, Dimitri A Diavatopoulos1,2. 1. Section Paediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center. 2. Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, The Netherlands.
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
Authors: Dinesh Devadoss; Arpan Acharya; Marko Manevski; Dominika Houserova; Michael D Cioffi; Kabita Pandey; Madhavan Nair; Prem Chapagain; Mehdi Mirsaeidi; Glen M Borchert; Siddappa N Byrareddy; Hitendra S Chand Journal: iScience Date: 2022-06-30
Authors: Rebecca P Payne; Stephanie Longet; James A Austin; Donal T Skelly; Wanwisa Dejnirattisai; Sandra Adele; Naomi Meardon; Sian Faustini; Saly Al-Taei; Shona C Moore; Tom Tipton; Luisa M Hering; Adrienn Angyal; Rebecca Brown; Alexander R Nicols; Natalie Gillson; Susan L Dobson; Ali Amini; Piyada Supasa; Andrew Cross; Alice Bridges-Webb; Laura Silva Reyes; Aline Linder; Gurjinder Sandhar; Jonathan A Kilby; Jessica K Tyerman; Thomas Altmann; Hailey Hornsby; Rachel Whitham; Eloise Phillips; Tom Malone; Alexander Hargreaves; Adrian Shields; Ayoub Saei; Sarah Foulkes; Lizzie Stafford; Sile Johnson; Daniel G Wootton; Christopher P Conlon; Katie Jeffery; Philippa C Matthews; John Frater; Alexandra S Deeks; Andrew J Pollard; Anthony Brown; Sarah L Rowland-Jones; Juthathip Mongkolsapaya; Eleanor Barnes; Susan Hopkins; Victoria Hall; Christina Dold; Christopher J A Duncan; Alex Richter; Miles Carroll; Gavin Screaton; Thushan I de Silva; Lance Turtle; Paul Klenerman; Susanna Dunachie Journal: Cell Date: 2021-10-16 Impact factor: 41.582
Authors: Thomas J Ketas; Devidas Chaturbhuj; Victor M Cruz Portillo; Erik Francomano; Encouse Golden; Sharanya Chandrasekhar; Gargi Debnath; Randy Díaz-Tapia; Anila Yasmeen; Kyle D Kramer; Tarek Munawar; Wilhelm Leconet; Zhen Zhao; Philip J M Brouwer; Melissa M Cushing; Rogier W Sanders; Albert Cupo; Per Johan Klasse; Silvia C Formenti; John P Moore Journal: Pathog Immun Date: 2021-06-07