Natural immunity and protection against variants in South African children through five COVID-19 waves: A prospective study

• Published in: International journal of infectious diseases 2025-01, Vol.150, p.107300, Article 107300
• Main Authors: Zar, Heather J., Workman, Lesley, MacGinty, Rae, Botha, Maresa, Johnson, Marina, Hunt, Adam, Burd, Tiffany, Nicol, Mark P., Flasche, Stefan, Quilty, Billy J., Goldblatt, David
• Format: Article
• Language: English
• Subjects: African; Antibodies; Antibodies, Viral - blood; Child; Child, Preschool; COVID-19; COVID-19 - epidemiology; COVID-19 - immunology; COVID-19 - prevention & control; Female; Humans; Immunity; Immunoglobulin G - blood; Male; Mother; Prospective Studies; Protective threshold; SARS-CoV-2; SARS-CoV-2 - immunology; South Africa - epidemiology; Spike Glycoprotein, Coronavirus - immunology; Vaccination; Variant
• ISSN: 1201-9712; 1878-3511; 1878-3511
• DOI: 10.1016/j.ijid.2024.107300

•Almost all children were seropositive by the end of wave V but with minimal disease.•Antibodies induced by natural exposure protected against subsequent infection.•Greatest protection for Beta and least for Omicron variants.•More immunoglobulin G are needed to protect children against Beta and Delta than mothers.•Maternal infection is the strongest factor associated with child seropositivity. Children have been largely spared from serious disease through the COVID-19 pandemic despite a high exposure to SARS-CoV-2. Antibody responses to exposure and their role in protecting children from subsequent variant infection remain poorly understood. This is a prospective cohort study of children in a South African community through ancestral/Beta/Delta/Omicron BA.1/BA.2 and BA.4/BA.5 SARS-CoV-2 waves (March 2020-October 2022). Health seeking behavior/illness was recorded and postwave serum samples measured for immunoglobulin (Ig) G to spike (S) (CoV2-S-IgG) by electrochemiluminescent immunosorbent assay. To estimate the 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. Despite little disease, 125 per 366 (34.2%) children (median age 6.7 years [interquartile range 5.99-7.4 years]) were seropositive after wave I, rising to 53.6%, 76.0%, and 96.2% and 99.2% after waves II (Beta), III (Delta), and IV and V (Omicron variants), 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. The levels of IgG specific for ancestral S antigen that provided a 50% protective threshold for the subsequent wave were lowest for the Beta and highest for the Omicron BA.1/BA.2 wave. In the multivariate analysis, maternal seropositivity (adjusted odds ratio = 2.57 [95% confidence interval: 1.72-3.82]) was strongly associated with child seropositivity. Children responded robustly to successive waves of SARS-CoV-2, mounting IgG responses to S antigen that were protective against subsequent waves. In the absence of vaccination, almost all children were seropositive after wave V but none were hospitalized, suggesting that natural immunity alone may be sufficient to protect children in a pandemic setting.