Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa

Heather J Zar; Rae MacGinty; Lesley Workman; Maresa Botha; Marina Johnson; Adam Hunt; Tiffany Burd; Mark P Nicol; Stefan Flasche; Billy J Quilty; David Goldblatt

doi:10.1016/j.eclinm.2022.101655

Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa

EClinicalMedicine. 2022 Sep 17:53:101655. doi: 10.1016/j.eclinm.2022.101655. eCollection 2022 Nov.

Authors

Affiliations

¹ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and SA-MRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
² Great Ormond Street Institute of Child Health Biomedical Research Centre, University College London & Great Ormond Street Children's Hospital NHS Foundation Trust, London, UK.
³ Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, Australia.
⁴ Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁵ Centre for Mathematical Modelling of Infectious Disease, London School of Hygiene and Tropical Medicine, UK.

Abstract

Background: More than half the global population has been exposed to SARS-CoV-2. Naturally induced immunity influences the outcome of subsequent exposure to variants and vaccine responses. We measured anti-spike IgG responses to explore the basis for this enhanced immunity.

Methods: A prospective cohort study of mothers in a South African community through ancestral/beta/delta/omicron SARS-CoV-2 waves (March 2020-February 2022). Health seeking behaviour/illness were recorded and post-wave serum samples probed for IgG to Spike (CoV2-S-IgG) by ECLISA. To estimate protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter for unvaccinated and vaccinated adults.

Findings: Despite little disease, 176/339 (51·9%) participants were seropositive following wave 1, rising to 74%, 89·8% and 97·3% after waves 2, 3 and 4 respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection with the greatest protection for beta and least for omicron. Vaccination induced higher CoV2-S-IgG in seropositive compared to naïve vaccinees. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% (95% CrI: 62, 72) following 1 vaccine dose, 63% (95% CrI: 63, 75) following 2 doses and only 11% (95% CrI: 7, 14) in unvaccinated during the omicron wave.

Interpretation: Naturally induced CoV2-S-IgG do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior immunity is more immunogenic than 2 doses in a naïve vaccinee and may provide adequate protection.

Funding: UK NIH GECO award (GEC111), Wellcome Trust Centre for Infectious Disease Research in Africa (CIDRI), Bill & Melinda Gates Foundation, USA (OPP1017641, OPP1017579) and NIH H3 Africa (U54HG009824, U01AI110466]. HZ is supported by the SA-MRC. MPN is supported by an Australian National Health and Medical Research Council Investigator Grant (APP1174455). BJQ is supported by a grant from the Bill and Melinda Gates Foundation (OPP1139859). Stefan Flasche is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 208812/Z/17/Z).

Keywords: Antibodies; COVID-19; Hybrid immunity; Protective threshold; SARS-CoV-2; Vaccination; Variant.

Grants and funding

MR/V028782/1/MRC_/Medical Research Council/United Kingdom