Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Abstract

IntroductionCurrent approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission.MethodsWe measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria®/Astrazeneca and/or Comirnaty®/Pfizer).ResultsWhile serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19.DiscussionAs breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Our results encourage further studies to explore the prognosis potential of anti-Spike-NTD IgA in saliva at predicting persistent smell and taste disorders.

Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk

“…This observation, however modest, was particularly evident in relation to circulating IgA levels, which were negative or close to the positivity threshold in individuals who experienced a breakthrough infection or reinfection. The extend of circulating IgA contribution to protection against infection is not clear and discrepancies regarding its association with mucosal IgA have been reported [42][43][44][45][46] . Circulating IgA function has been described in relation to induction of proinflammatory cellular functions, such as phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), degranulation, antigen presentation, and release of inflammatory mediators 47,48 .…”

The immunobiology of SARS-CoV-2 infection and vaccine responses: potential influences of cross-reactive memory responses and aging on efficacy and off-target effects

“…Commonly used mRNA vaccines targeting the CoV2 S protein have been shown to be efficacious in K18 mice by generating robust antibody responses ( 56 – 60 ). Similarly, IgM ( 61 – 65 ), IgG ( 26 – 28 , 66 – 69 ), and IgA ( 66 , 70 – 72 ) mouse antibody kinetics mirroring those observed in humans have been demonstrated. While the vast majority of these vaccine studies have centered on antibody responses, T cell responses have also been characterized ( 72 – 74 ).…”

Subclinical SARS-CoV-2 Infections and Endemic Human Coronavirus Immunity Shape SARS-CoV-2 Saliva Antibody Responses

“…These results are consistent with other studies that have identified clear differences in humoral immune responses between vaccine-only groups and hybrid immune groups. 47,56,57 These results suggest that development of anti-SCV2 spike IgA and SIgA in the saliva requires antigen exposure in the NALT to generate a local mucosal immune response through activation of tissue-resident memory B cells.…”