Immunity to <i>Streptococcus pyogenes</i> and Common Respiratory Viruses at Age 0 to 4 Years After COVID-19 Restrictions
Kitt Dokal, Samuel Channon‐Wells, Catherine H. Davis, Diego Estrada‐Rivadeneyra, Kristin K. Huse, Amelia M. Lias, Shea Hamilton, Rebecca Guy, Theresa Lamagni, Samuel J. Nichols, Andrew Taylor, Philipp Agyeman, Amutha Anpananthar, Romain Basmaci, Enitan D. Carrol, Michael J. Carter, Tisham De, Marien I. de Jonge, Marieke Emonts, Leire Estramiana Elorrieta, Katy Fidler, Mojca Kolnik, Taco W. Kuijpers, Federico Martinón‐Torres, Henriëtte A. Moll, Marine Mommert, Samira Neshat, Maggie Nyirenda-Nyang’wa, Séan O’Riordan, DR Owens, Nazima Pathan, Stéphane Paulus, Mark Peters, Marko Pokorn, Andrew J Pollard, Irene Rivero‐Calle, Pablo Rojo, Lorenza Romani, Prita Rughani, Luregn J. Schlapbach, Nina A. Schweintzger, Ching‐Fen Shen, Artur Sulik, Μαρία Τσολιά, Effua Usuf, Michiel van der Flier, Clementien Vermont, Ulrich von Both, Paul Wellman, Victoria Wright, Shunmay Yeung, Dace Zavadska, Aubrey J. Cunnington, Colin G. Fink, Jethro Herberg, Myrsini Kaforou, Shiranee Sriskandan, Michael Levin, Tom Parks, Michael Levin, Aubrey Cunnington, Jethro Herberg, Myrsini Kaforou, Victoria J. Wright, Evangelos Bellos, Claire Broderick, Samuel Channon-Wells, Samantha Cooray, Tisham De, Giselle D'Souza, Amedine Duret, Anikta Duseja, Leire Estamiana Ellorrieta, Diego Estrada-Rivadeneyra, Rachel Gallassini, Dominic Habgood-Coote, Shea Hamilton, Heather Jackson, James Kavanagh, Ilana Keren, Mahdi Moradi Marjeneh, Stephanie Menikou, Samuel Nichols, Ruud Nijman, Harsita Patel, Ivana Pennisi, Oliver Powell, Ruth Reid, Priyen Shah, Ortensia Vito, Elizabeth Whittaker, Clare Wilson, Rebecca Womersley, Amina Abdulla, Sarah Darnell, Sobia Mustafa, Pantelis Georgiou, Jesus Rodriguez-Manzano, Nicolas Moser, Michael Carter
Abstract
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.