Mucosal immunity to severe acute respiratory syndrome coronavirus 2 infection

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.

Antibody Responses to SARS-CoV-2 mRNA Vaccines Are Detectable in Saliva

“…SARS-CoV-2 is typically transmitted nasally or orally and infects cells in the mucosae of the respiratory and gastrointestinal tracts [5][6][7][8]. Although serum NAbs are a correlate of protection against COVID-19 [9,10], mucosal antibodies might directly prevent or limit virus acquisition by the nasal, oral, and conjunctival routes [5][6][7][8]11]. Indeed, antibodies in the respiratory tract or oral cavity have been deemed important to protection against a human-to-human transmitted hantavirus, influenza virus, and respiratory syncytial virus [12][13][14].…”

12-month SARS-CoV-2 antibody persistency in a Tyrolean COVID-19 cohort

“…Moreover, NAb assays only assess limited aspects of clinical immunity in that the interaction between test sera, viruses, and cultured cells susceptible to viral infection are included. There are several details that are not analyzed, such as cellular immunity overall, tissue-based cellular immunity [ 20 ], tissue-based humoral immunity with mucosal IgA not correlating well with circulating IgA [ 21 ] and of course immune memory [ 1 , 22 ], which seems to be persisting as of now; however, using antibody tests as surrogates even if not fully validated seems more practical. Assessing long-term clinical immunity required probably 10,000s of unvaccinated convalescents followed prospectively over many years which seems hardly doable at least for the time being.…”

Study on the mucosal and serological immune response to the Novel Coronavirus (SARS-CoV-2) vaccines

“…Sufficiently high concentrations of NAb in the NELF can block the attachment of virus to the host cell receptor. The SIgA is known to trap virus efficiently and facilitates the removal of such by the mucociliary beating (25), to neutralize virus particles with epithelial cell and lamina propria (17), and has anti-inflammatory properties (26).…”