Immunity to Streptococcus pyogenes and Common Respiratory Viruses at Age 0 to 4 Years After COVID-19 Restrictions.

Importance The upsurge in invasive disease caused by Streptococcus pyogenes among children reported in several European countries during 2022 to 2023 has not been fully explained. Objective To evaluate whether changes in the circulation of common respiratory pathogens associated with the introduction of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic were associated with acquisition of immunity to S pyogenes and common respiratory viruses. Design, Setting, And Participants This cross-sectional study recruited children with suspected infection and afebrile control participants at hospitals in 10 European countries. Data were collected before (September 2016 to March 2020) and after (April 2020 to July 2023) the introduction of NPIs. Main Outcomes And Measures Molecular detection of bacterial and viral pathogens on throat swabs and age-stratified total serum immunoglobin G (IgG) reactivity to S pyogenes cell wall extract from 2 strains, respiratory syncytial virus (RSV), 5 influenza viruses, 4 common cold coronaviruses, and SARS-CoV-2, measured by immunoassay. Results Throat swabs from 1942 children aged 0 to 4 years were tested for respiratory pathogens (1449 recruited before introduction of NPIs [median (IQR) age, 19.7 (8.2-38.1) months; 798 (55.1%) male]; 493 recruited after [median (IQR) age, 20.7 (9.7-38.1) months; 269 (54.7%) male]). A decrease in detection of S pyogenes, RSV, common cold coronaviruses, and influenza viruses was observed between March 2020 to July 2021, corresponding to the maximal period of NPIs. Antibodies to S pyogenes were measured in 252 children recruited before NPIs and 200 thereafter. Antibodies to viral antigens were measured in 230 children before NPIs and 92 thereafter. Total IgG to S pyogenes and RSV was significantly lower in children aged 3 to 4 years recruited after NPI introduction compared with those recruited before (S pyogenes emm1 strain: after, 67 participants; median [IQR] 0.13 [0.44-0.44] relative units [RU]; before, 87 participants; median [IQR] 0.35 [0.10-0.65] RU; P = .007. RSV: after, 30 participants; median [IQR] 49.6 [31.1-120.7] mesoscale units [MU]/1000; before, 76 participants; median [IQR] 141.8 [78.1-423.1] MU/1000; P < .001). No such differences were observed for children aged 0 to 2 years or for individual influenza viruses or SARS-CoV-2. Conclusions And Relevance In this cross-sectional study, there was a significant reduction in serum antibodies to S pyogenes and RSV in children aged 3 to 4 years after introduction of NPIs. Equivalent to approximately a 1-year delay in acquisition of immunity, these data suggest a putative biological basis for the 2022 to 2023 upsurge in severe S pyogenes infections in this age group.