TY - JOUR
T1 - Immunity to Streptococcus pyogenes and Common Respiratory Viruses at Age 0 to 4 Years After COVID-19 Restrictions
AU - Dokal, Kitt
AU - Channon-Wells, Samuel
AU - Davis, Catherine
AU - Estrada-Rivadeneyra, Diego
AU - Huse, Kristin K
AU - Lias, Amelia
AU - Hamilton, Shea
AU - Guy, Rebecca L
AU - Lamagni, Theresa
AU - Nichols, Sam
AU - Taylor, Andrew
AU - Agyeman, Philipp K A
AU - Anpananthar, Amutha
AU - Basmaci, Romain
AU - Carrol, Enitan D
AU - Carter, Michael J
AU - De, Tisham
AU - de Jonge, Marien I
AU - Emonts, Marieke
AU - Elorrieta, Leire Estramiana
AU - Fidler, Katy
AU - Kolnik, Mojca
AU - Kuijpers, Taco W
AU - Martinon-Torres, Federico
AU - Moll, Henriette
AU - Mommert-Tripon, Marine
AU - Neshat, Samira
AU - Nyirenda-Nyang'wa, Maggie
AU - O'Riordan, Sean
AU - Owens, Daniel R
AU - Pathan, Nazima
AU - Paulus, Stephane
AU - Peters, Mark J
AU - Pokorn, Marko
AU - Pollard, Andrew J
AU - Rivero-Calle, Irene
AU - Rojo, Pablo
AU - Romani, Lorenza
AU - Rughani, Prita
AU - Schlapbach, Luregn J
AU - Schweintzger, Nina A
AU - Shen, Ching-Fen
AU - Sulik, Artur
AU - Tsolia, Maria
AU - Usuf, Effua
AU - van der Flier, Michiel
AU - Vermont, Clementien
AU - von Both, Ulrich
AU - Wellman, Paul
AU - Wright, Victoria J
AU - Yeung, Shunmay
AU - Zavadska, Dace
AU - Cunnington, Aubrey J
AU - Fink, Colin
AU - Herberg, Jethro
AU - Kaforou, Myrsini
AU - Sriskandan, Shiranee
AU - Levin, Michael
AU - Parks, Tom
AU - PERFORM and DIAMONDS consortiums
A2 - Laivacuma, Sniedze
A2 - Rudzāte, Aleksandra
A2 - Stoldere, Diāna
A2 - Bārzdiņa, Arta
A2 - Barzdina, Elza
A2 - Madelāne, Monta
A2 - Gravele, Dagne
A2 - Svile, Dace
A2 - Balode, Anda
A2 - Gardovska, Dace
A2 - Grope, Ilze
A2 - Meiere, Anija
A2 - Nokalna-Spale, Ieva
A2 - Pavāre, Jana
A2 - Pučuka, Zanda
A2 - Urbāne, Urzula Nora
N1 - Publisher Copyright:
© 2025 Dokal K et al.
PY - 2025/10/15
Y1 - 2025/10/15
N2 - 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.
AB - 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.
KW - Humans
KW - Streptococcus pyogenes/immunology
KW - COVID-19/prevention & control
KW - Infant
KW - Male
KW - Female
KW - Child, Preschool
KW - Cross-Sectional Studies
KW - Streptococcal Infections/immunology
KW - SARS-CoV-2/immunology
KW - Europe/epidemiology
KW - Infant, Newborn
KW - Immunoglobulin G/blood
KW - Antibodies, Viral/blood
UR - https://www.scopus.com/pages/publications/105018647084
U2 - 10.1001/jamanetworkopen.2025.37808
DO - 10.1001/jamanetworkopen.2025.37808
M3 - Article
C2 - 41091464
SN - 2574-3805
VL - 8
JO - JAMA network open
JF - JAMA network open
IS - 10
M1 - e2537808
ER -