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

Kitt Dokal; Samuel Channon-Wells; Catherine Davis; Diego Estrada-Rivadeneyra; Kristin K. Huse; Amelia Lias; Shea Hamilton; Rebecca L. Guy; Theresa Lamagni; Sam Nichols; Andrew Taylor; Philipp K.A. 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 Martinon-Torres; Henriette Moll; Marine Mommert-Tripon; Samira Neshat; Maggie Nyirenda-Nyang'wa; Sean O'Riordan; Daniel R. Owens; Nazima Pathan; Stephane Paulus; Mark J. 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; Maria Tsolia; Effua Usuf; Michiel van der Flier; Clementien Vermont; Ulrich von Both; Paul Wellman; Victoria J. Wright

doi:10.1001/jamanetworkopen.2025.37808

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

Kitt Dokal, Samuel Channon-Wells, Catherine Davis, Diego Estrada-Rivadeneyra, Kristin K. Huse, Amelia Lias, Shea Hamilton, Rebecca L. Guy, Theresa Lamagni, Sam Nichols, Andrew Taylor, Philipp K.A. Agyeman, Amutha Anpananthar, Romain Basmaci, Enitan D. Carrol, Michael J. Carter, Tisham De, Marien I. de Jonge, Marieke Emonts, Leire Estramiana ElorrietaKaty Fidler, Mojca Kolnik, Taco W. Kuijpers, Federico Martinon-Torres, Henriette Moll, Marine Mommert-Tripon, Samira Neshat, Maggie Nyirenda-Nyang'wa, Sean O'Riordan, Daniel R. Owens, Nazima Pathan, Stephane Paulus, Mark J. 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, Maria Tsolia, Effua Usuf, Michiel van der Flier, Clementien Vermont, Ulrich von Both, Paul Wellman, Victoria J. Wright,

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	e2537808
Pages (from-to)	1-16
Number of pages	16
Journal	JAMA network open
Volume	8
Issue number	10
DOIs	https://doi.org/10.1001/jamanetworkopen.2025.37808
Publication status	Published - 15 Oct 2025

Keywords

Humans
Streptococcus pyogenes/immunology
COVID-19/prevention & control
Infant
Male
Female
Child, Preschool
Cross-Sectional Studies
Streptococcal Infections/immunology
SARS-CoV-2/immunology
Europe/epidemiology
Infant, Newborn
Immunoglobulin G/blood
Antibodies, Viral/blood

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Dokal, K., Channon-Wells, S., Davis, C., Estrada-Rivadeneyra, D., Huse, K. K., Lias, A., Hamilton, S., Guy, R. L., Lamagni, T., Nichols, S., Taylor, A., Agyeman, P. K. A., Anpananthar, A., Basmaci, R., Carrol, E. D., Carter, M. J., De, T., de Jonge, M. I., Emonts, M. (2025). Immunity to Streptococcus pyogenes and Common Respiratory Viruses at Age 0 to 4 Years After COVID-19 Restrictions. JAMA network open, 8(10), 1-16. Article e2537808. https://doi.org/10.1001/jamanetworkopen.2025.37808

@article{9a3220129e734755a19af78ceda26cf2,

title = "Immunity to Streptococcus pyogenes and Common Respiratory Viruses at Age 0 to 4 Years After COVID-19 Restrictions",

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.",

keywords = "Humans, Streptococcus pyogenes/immunology, COVID-19/prevention \& control, Infant, Male, Female, Child, Preschool, Cross-Sectional Studies, Streptococcal Infections/immunology, SARS-CoV-2/immunology, Europe/epidemiology, Infant, Newborn, Immunoglobulin G/blood, Antibodies, Viral/blood",

author = "Kitt Dokal and Samuel Channon-Wells and Catherine Davis and Diego Estrada-Rivadeneyra and Huse, \{Kristin K.\} and Amelia Lias and Shea Hamilton and Guy, \{Rebecca L.\} and Theresa Lamagni and Sam Nichols and Andrew Taylor and Agyeman, \{Philipp K.A.\} and Amutha Anpananthar and Romain Basmaci and Carrol, \{Enitan D.\} and Carter, \{Michael J.\} and Tisham De and \{de Jonge\}, \{Marien I.\} and Marieke Emonts and Elorrieta, \{Leire Estramiana\} and Katy Fidler and Mojca Kolnik and Kuijpers, \{Taco W.\} and Federico Martinon-Torres and Henriette Moll and Marine Mommert-Tripon and Samira Neshat and Maggie Nyirenda-Nyang'wa and Sean O'Riordan and Owens, \{Daniel R.\} and Nazima Pathan and Stephane Paulus and Peters, \{Mark J.\} and Marko Pokorn and Pollard, \{Andrew J.\} and Irene Rivero-Calle and Pablo Rojo and Lorenza Romani and Prita Rughani and Schlapbach, \{Luregn J.\} and Schweintzger, \{Nina A.\} and Shen, \{Ching Fen\} and Artur Sulik and Maria Tsolia and Effua Usuf and \{van der Flier\}, Michiel and Clementien Vermont and \{von Both\}, Ulrich and Paul Wellman and Wright, \{Victoria J.\}",

note = "Publisher Copyright: {\textcopyright} 2025 Dokal K et al.",

year = "2025",

month = oct,

day = "15",

doi = "10.1001/jamanetworkopen.2025.37808",

language = "English",

volume = "8",

pages = "1--16",

journal = "JAMA network open",

issn = "2574-3805",

publisher = "American Medical Association",

number = "10",

}

Dokal, K, Channon-Wells, S, Davis, C, Estrada-Rivadeneyra, D, Huse, KK, Lias, A, Hamilton, S, Guy, RL, Lamagni, T, Nichols, S, Taylor, A, Agyeman, PKA, Anpananthar, A, Basmaci, R, Carrol, ED, Carter, MJ, De, T, de Jonge, MI, Emonts, M, Elorrieta, LE, Fidler, K, Kolnik, M, Kuijpers, TW, Martinon-Torres, F, Moll, H, Mommert-Tripon, M, Neshat, S, Nyirenda-Nyang'wa, M, O'Riordan, S, Owens, DR, Pathan, N, Paulus, S, Peters, MJ, Pokorn, M, Pollard, AJ, Rivero-Calle, I, Rojo, P, Romani, L, Rughani, P, Schlapbach, LJ, Schweintzger, NA, Shen, CF, Sulik, A, Tsolia, M, Usuf, E, van der Flier, M, Vermont, C, von Both, U, Wellman, P, Wright, VJ 2025, 'Immunity to Streptococcus pyogenes and Common Respiratory Viruses at Age 0 to 4 Years After COVID-19 Restrictions', JAMA network open, vol. 8, no. 10, e2537808, pp. 1-16. https://doi.org/10.1001/jamanetworkopen.2025.37808

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.

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

AN - SCOPUS:105018647084

SN - 2574-3805

VL - 8

SP - 1

EP - 16

JO - JAMA network open

JF - JAMA network open

IS - 10

M1 - e2537808

ER -

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

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