Development of hybrid immunity during a period of high incidence of Omicron infections
Authors: Frei Anja , Kaufmann Marco , Amati Rebecca , Butty Dettwiler Audrey , von Wyl Viktor , Annoni Anna Maria , Vincentini Julia , Pellaton Céline , Pantaleo Giuseppe , Fehr Jan S , D'Acremont Valérie , Bochud Murielle , Albanese Emiliano , Puhan Milo A ,   Corona Immunitas Research Group, Albanese Emiliano , Amati Rebecca , Amendola Antonio , Anagnostopoulos Alexia , Anker Daniela , Annoni Anna Maria , Aschmann Hélène , Azman Andrew , Bal Antoine , Ballouz Tala , Baysson Hélène , Bezani Kleona , Blattmann Annette , Bleich Patrick , Bochud Murielle , Bodenmann Patrick , Rumley Gaëlle Bryand , Buttaroni Peter , Dettwiler Audrey Butty , Camerini Anne Linda , Chiolero Arnaud , Chocano-Bedoya Patricia Orializ , Collombet Prune , Corna Laurie , Crivelli Luca , Cullati Stéphane , D'Acremont Valérie , Santos Diana Sofia Da Costa , Deschamps Agathe , D’Ippolito Paola , Domenghino Anja , Dubos Richard , Dumont Roxane , Duperrex Olivier , Dupraz Julien , Egger Malik , El-May Emna , El Merjani Nacira , Engler Nathalie , Epure Adina Mihaela , Erksam Lukas , Estoppey Sandrine , Fadda Marta , Faivre Vincent , Fehr Jan , Felappi Andrea , Fiordelli Maddalena , Flahault Antoine , Fornerod Luc , Corti Cristina Fragoso , Francioli Natalie , Frangville Marion , Frank Irène , Franscella Giovanni , Frei Anja , Geigges Marco , Nusslé Semira Gonseth , Graindorge Clément , Guessous Idris , Harju Erika , Harnal Séverine , Imboden Medea , Jendly Emilie , Jeong Ayoung , Kahlert Christian R , Kaiser Laurent , Kaufmann Laurent , Kaufmann Marco , Keidel Dirk , Kessler Simone , Kohler Philipp , Krähenbühl Christine , Kriemler Susi , Lamour Julien , Levati Sara , Lescuyer Pierre , Loizeau Andrea , Lorthe Elsa , Luedi Chantal , Magnin Jean-Luc , Martinez Chantal , Masserey Eric , Menges Dominik , Michel Gisela , Morese Rosalba , Mösli Nicolai , Noël Natacha , Paris Daniel Henry , Pasquier Jérôme , Pennacchio Francesco , Pfister Stefan , Piumatti Giovanni , Poulain Géraldine , Probst-Hensch Nicole , Pugin Caroline , Puhan Milo , Pullen Nick , Radtke Thomas , Rasi Manuela , Richard Aude , Richard Viviane , Robert Claude-François , Rodondi Pierre-Yves , Rodondi Nicolas , Sabatini Serena , Samir Khadija , Zozaya Javier Sanchis , Schlüter Virginie , Schmid Alexia , Schneider Valentine , Schüpbach Maria , Schwab Nathalie , Semaani Claire , Speierer Alexandre , Steiner-Dubuis Amélie , Stringhini Silvia , Tancredi Stefano , Testini Stéphanie , Thabard Julien , Tonolla Mauro , Troillet Nicolas , Ulyte Agne , Vassaux Sophie , Vermes Thomas , Villers Jennifer , von Wyl Viktor , Wagner Cornelia , Wenger Rylana , West Erin , Wisniak Ania , Witzig Melissa , Zaballa María-Eugenia , Zens Kyra , Zuppinger Claire 
Published: July 2023

Abstract

Background
Seroprevalence and the proportion of people with neutralizing activity (functional immunity) against SARS-CoV-2 variants were high in early 2022. In this prospective, population- based, multi-region cohort study, we assessed the development of functional and hybrid immunity (induced by vaccination and infection) in the general population during this period of high incidence of infections with Omicron variants.

Methods
We randomly selected and assessed individuals aged ≥16 years from the general population in southern (n = 739) and north-eastern (n = 964) Switzerland in March 2022. We assessed them again in June/July 2022, supplemented with a random sample from western (n = 850) Switzerland. We measured SARS-CoV-2 specific IgG antibodies and SARS-CoV-2 neutralizing antibodies against three variants (ancestral strain, Delta, Omicron).

Results
Seroprevalence remained stable from March 2022 (97.6%, n = 1894) to June/July 2022 (98.4%, n = 2553). In June/July, the percentage of individuals with neutralizing capacity against ancestral strain was 94.2%, against Delta 90.8% and against Omicron 84.9%, and 50.6% developed hybrid immunity. Individuals with hybrid immunity had highest median levels of anti-spike IgG antibodies titres [4518 World Health Organization units per millilitre (WHO U/mL)] compared with those with only vaccine- (4304 WHO U/mL) or infection- (269 WHO U/mL) induced immunity, and highest neutralization capacity against ancestral strain (hybrid: 99.8%, vaccinated: 98%, infected: 47.5%), Delta (hybrid: 99%, vaccinated: 92.2%, infected: 38.7%) and Omicron (hybrid: 96.4%, vaccinated: 79.5%, infected: 47.5%).

Conclusions
This first study on functional and hybrid immunity in the Swiss general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less so for the general population.