Impact of COVID‐19 on Mucosal Immunity and Antibody Responses in COVID Vaccinees

Background & Objectives: SARS-CoV2 infection initiates at mucosal surfaces and mucosal immunity may influence the nature and severity of infection. Little is known about their induction by vaccination in COVID-19 convalescents. Methods: Sera from 205 healthcare workers was collected one-month after first Covishield vaccination and 1/3/6-months after second vaccination, while paired sera and stimulated whole mouth fluid (SWMF) was collected 1/3/6-months after third vaccination (N=10) and at 0/30/90-days after a COVID-19 episode (N=8). All were tested for anti-SARS-CoV2 spike antibodies by ECLIA/ELISA and cytokines by ELISA/CBA. Results: One-month post-second-vaccination, serum antibodies had increased significantly (6-fold) in the COVID-19-naïve group (CNG), but declined (1.5-fold) in the previously COVID-19-exposed group (CEG), who already had high antibody titres. The serum regulatory cytokine IL-10 levels were higher after three antigen exposures (p=0.0002). New infections or reinfections occurred in 44% of CNG and 27% of CEG (p< 0.01). The mucosal cytokine IL-17 levels were significantly higher in the CEG. Salivary IgG/IgA and secretory IgA antibodies were detectable both after vaccination and COVID-19. Adaptive immunity cytokines after three vaccinations were barely detectable. Innate cytokines (MIG, MCP-1, IL-8, IL-1β) were higher and sustained in SWMF in contrast to serum. Conclusions: Two vaccinations in CNG resulted in an expected antibody boost, but that a second vaccination in CEG induced antibody anergy. Rapidly declining serum antibodies and minimal T cell cytokines raise concerns over their durability in subsequent virus exposures. Sustained innate cytokines and IgA antibodies emanating from the oral mucosa may result in early virus clearance and impact morbidity.