Development of hybrid immunity during a period of high incidence of infections with Omicron subvariants: A prospective population based multi-region cohort study

Abstract

Background Seroprevalence and the proportion of people with neutralizing activity against SARS-CoV-2 variants was high in early 2022. Since it is unclear how immunity in the general population evolves, the aim of this study was to assess the development of functional and hybrid immunity in the general population during a period of high incidence of infections with Omicron variants. Methods This prospective population based multi-region cohort study is part of the Corona Immunitas research programme in Switzerland. In March 2022, we randomly selected individuals from the general population in southern (canton of Ticino) and north-eastern (canton of Zurich) Switzerland, who were assessed again in June/July 2022. We supplemented the June/July 2022 sample with a random sample from western Switzerland (canton of Vaud). We assessed SARS-CoV-2 specific IgG antibodies against spike and nucleocapsid proteins and the presence of SARS-CoV-2 neutralising antibodies against three variants (wildtype, Delta, Omicron). Findings In June/July 2022, seroprevalence was >98% in 2553 individuals from the general Swiss population. The proportion of individuals with neutralising antibodies against wildtype, Delta, and Omicron was 94.2%, 90.8%, and 84.9%, and at least 51% of the participants developed hybrid immunity. Individuals with hybrid immunity had, compared to those with only vaccine- or infection-induced immunity, highest levels of both, anti-spike IgG antibodies titres (4518 vs. 4304 vs. 269 WHO U/ml) and neutralisation capacity against wildtype (99.8% vs. 98% vs. 47.5%), Delta (99% vs. 92.2% vs. 38.7%), and Omicron (96.4% vs. 79.5% vs. 47.5%). Interpretation This first study on functional and hybrid immunity in the general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization in the general populations support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less strongly recommended for individuals in the general population.

Serial cross-sectional estimation of vaccine-and infection-induced SARS-CoV-2 seroprevalence in British Columbia, Canada

“…Multiple immunological, epidemiological and modelling studies suggest that having had both vaccination and infection exposures contributes to stronger, broader and more durable hybrid immunity than with either exposure alone, especially against severe outcomes. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] The extent to which such exposure history should guide recommendations regarding booster doses depends on several factors, recognizing that a large proportion may not even be aware of their previous infection status. 48 Moreover, the antigenic relatedness and immunological interactions between previously infecting viruses, the original monovalent vaccines, more recently updated bivalent vaccine strains, and currently circulating or emerging variants are complex and dynamic.…”

Longitudinal Humoral and Cell-Mediated Immune Responses in a Population-Based Cohort in Zurich, Switzerland between March and June 2022 - Evidence for Protection against Omicron SARS-CoV-2 Infection by Neutralizing Antibodies and Spike-specific T cell responses

“…98.4% of participants were S-IgG seropositive and 23.2% were N-IgG seropositive (Fig.1A) 21,22 . 96.8%, 93.7% and 89.5% of participants had detectable neutralization IC50 values to WT, delta and omicron viral variants, respectively.…”

“…73.7% were aged 16-64 and 26.3% were 65+. 93.5% reported previous SARS-CoV-2 vaccination; 90.8% were fully vaccinated (2+ vaccine doses) and 72.1% had received at least one booster (3+ vaccine doses) 21,22 . 32.6% of participants reported a previous SARS-CoV-2 infection (defined as having received a positive PCR or antigen test result) at some point from the pandemic start up to the study visit.…”

“…While antibody responses among individuals in the Zurich area, and throughout Switzerland have been well-described [21][22][23][24] , much less is known regarding population-level T cell responsiveness to SARS-CoV-2. Here, we utilized an interferon (IFN)-gamma release assay (IGRA) based on short-term culture of whole blood with SARS-CoV-2-specific peptides to assess T cell responses, which demonstrated good concordance with an ELISpot assay which we used previously 14 .…”

Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses

“…As a result, a large number of individuals in highly vaccinated populations now have so-called hybrid immunity, generated through a combination of vaccination and infection. A multi-region cohort study in Switzerland estimated that at least 51% of the population had hybrid immunity by July 2022, with 85% having some degree of omicron-specific antibody immunity (7).…”