Disruption of Epidemic Patterns in Community-Acquired Respiratory Infections Post-Covid-19 in France: A 5-Year Analysis Using the French Pediatric and Ambulatory Research of Infectious Diseases Network

Abstract

After the lifting of the nonpharmaceutical interventions introduced during the COVID-19 pandemic. Enterovirus reappeared 16 months after COVID-19 onset; bronchiolitis, 33 months; group A Streptococcus infections, 36 months; pneumonia, 45 months and pertussis, 51 months. These differences across pathogens shed light on differences in herd immunity durability and pathogen-specific vulnerability.

The implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic profoundly altered the epidemiology of numerous infectious diseases.¹ The first indication of such disruption emerged from the Southern Hemisphere.¹ Just a few months into the pandemic, with widespread application of NPIs, an atypical respiratory syncytial virus (RSV) epidemic pattern was documented.¹ Early projections by Baker et al² had warned of possible resurgences of RSV and influenza as NPIs were eased. This gave rise to the concept of “immune debt”—a hypothesis suggesting that prolonged reduced exposure to common pathogens weakens population-level immune stimulation, resulting in increased susceptibility and diminished herd immunity.³ Notably, the decline in pathogen circulation, including asymptomatic infections, may have undermined specific immunity without indicating any inherent immune deficiency, but rather a lack of antigenic challenge. According to this immune debt concept, because the duration of immune protection is known to vary by pathogen, the timing of the resurgence of pediatric respiratory infections could vary by pathogen.

To test this hypothesis, we took advantage of the Pediatric and Ambulatory Research of Infectious Diseases (PARI) study, which has systematically monitored pediatric infectious disease epidemiology in ambulatory care since 2018. We now have valuable longitudinal data encompassing both pre- and post-COVID periods.^4,5 This current study evaluated the resurgence delays of several pediatric respiratory infections in the post-COVID-19 context.

METHODS

Since January 2018, 160 ambulatory pediatricians trained in infectious diseases and using standardized software (AxiSanté 5 Infansoft, CompuGroup Medical, France) have participated in a nationwide prospective surveillance program (PARI). Viral pathogens (SARS-CoV-2, RSV and influenza A/B) were identified via rapid antigen testing, distributed at no cost to both pediatricians and patients. For hand, foot and mouth disease or herpangina cases, buccal/throat swabs were submitted to the national reference center for enterovirus testing using a pan-enterovirus assay (Enterovirus R-GENE, bioMérieux, France).⁶ Group A Streptococcus (GAS) was identified by rapid antigen tests for pharyngitis, tonsillopharyngitis and scarlet fever.^5,7 For pneumonia, CRP was performed according to the clinical status of the patient. All these infectious disease diagnoses were automatically extracted from electronic medical records,^4,5 so we included all children who were visiting one of the participating ambulatory pediatricians and had one of the above-listed diagnoses.

To analyze the delay between the start of the COVID-19 pandemic and the resurgence of infection with each pathogen, we first computed the weekly number of each pathogen over the whole study period. Then, we considered March 2020 as the start of the national lockdown for COVID-19, and the peak number of diagnoses of infection with each pathogen as being the outbreak peak.³ Finally, we compared this delay across all pathogens.

Data were analyzed by using STATA 19 (StataCorp 2019, College Station, TX). Informed consent was waived as per protocol unless parents objected. Ethical approval was granted by the French National Commission on Informatics and Liberty (no. 1921226), CHI Créteil Hospital ethics committee, and ClinicalTrials.gov (NCT04471493).

RESULTS

Between January 2018 and June 2025, the PARI outpatient network recorded 26,286 cases of bronchiolitis, 20,898 of enterovirus infections, 35,693 of influenza, 16,177 of GAS+ pharyngitis/scarlet fever, 3402 of pneumonia and 552 of pertussis. Figure 1 shows the heightened postpandemic resurgence intensity and delayed reemergence of many diseases. The timing of the highest peak across all monitored diseases varied depending on the pathogen: after COVID-19 onset, enterovirus, 16 months; bronchiolitis, 33 months; GAS+ pharyngitis/scarlet fever, 36 months; pneumonia, 45 months and pertussis, the longest delay, 51 months. Across all these diseases, frequency returned to baseline during the year following the highest peak. Influenza returned more rapidly, although its postpandemic dynamics varied across seasons: 2021/22 (influenza A, 99%), 2022/23 (influenza A, 58%; influenza B, 42%), 2023/24 (influenza A, 93%) and 2024/25 (influenza A, 61%; influenza B, 39%) (see Figure, Supplemental Digital Content 1, https://links.lww.com/INF/G417). For pneumonia, Figure, Supplemental Digital Content 2, https://links.lww.com/INF/G417, presents the distribution of cases according to the study years and the levels of CRP. The pneumonia peak observed in 2024 may have been attributable to Mycoplasma pneumoniae for 3 reasons: CRP levels below 80 mg/dL, the epidemic intensity, approximately 3-fold higher than in previous years, and its concomitance in hospitalized patients, both adults and children.⁸

FIGURE 1.

Resurgence intensity and delayed reemergence of pathogen-caused infections: enterovirus infection, bronchiolitis, group A Streptococcus pharyngitis/scarlet fever, pneumonia, and pertussis.

DISCUSSION

In many settings, the lifting of NPIs led to atypical resurgences of infection with several pathogens—RSV, GAS, influenza, Mycoplasma pneumoniae, Bordetella pertussis and meningococcus—highlighting the pandemic’s long-lasting epidemiologic effects. The PARI outpatient network, operating uniformly across France since 2018, allowed for unbiased tracking of these delayed and intensified disease rebounds. Despite identical NPIs, health systems and pediatric care structures nationwide, pathogen-specific resurgence timelines varied markedly. Therefore, the observed differences between diseases may not be attributable solely to the duration of immunity but also to other factors (strains’ characteristics, co-infections, weather, seasonality, transmission dynamics, …). Nevertheless, irrespective of the pathogen, the occurrence of an epidemic with substantial pathogen circulation consistently indicates a decline in herd immunity. Our results primarily focused on the timing of the highest peak for each pathogen. However, for bronchiolitis and pneumonia, an earlier but smaller peak was observed, which may be explained by the gradual relaxation of NPIs. Epidemic cycles are well recognized for many infectious diseases, particularly those transmitted via the respiratory route. For example, epidemics of RSV, influenza, human metapneumovirus and enterovirus occur annually. For other pathogens—sometimes despite mature vaccination programs and high routine vaccination coverage—the intervals between epidemic peaks are longer: approximately 5 years for pertussis and 3–7 years for Mycoplasma.^1,9,10 Pertussis resurgence—despite high vaccine coverage maintained in France during COVID-19 periods—supports the acellular vaccine’s limited durability and negligible effect on carriage or transmission.¹⁰ NPIs likely suppressed B. pertussis circulation for extended periods, impeding natural immunity reinforcement and fostering a susceptible population. This study highlights that NPIs, by limiting the transmission of respiratory pathogens and reducing specific immunity, contributed to altered epidemic dynamics. In some cases, the timing of outbreaks shifted; more strikingly, epidemic intensity reached unprecedented levels. These findings strongly support a major role of population-level immunity in determining epidemic magnitude.

Serologic studies support this immune debt. In New Zealand, antibody titers against RSV and Streptococcus pyogenes decreased significantly in adults from 2020 to 2023.¹¹ Furthermore, 1 pediatric study reported a significant decrease in global IgG level after NPI application and an increase after relaxation of these measures.¹² These findings call for long-term surveillance not only of disease incidence but also of population-level immunity renewal through infection or vaccination.

We may now be entering a “re-equilibration phase,” during which co-infections—particularly those involving RSV and Streptococcus pneumoniae—may amplify disease burden.

In summary, the pandemic revealed how immune dynamics shape infectious disease cycles: the postpandemic rebounds of infections were heterogeneous and abnormally intense, thus underscoring the concept of immune debt.^3,11,12 Moreover, we believe that our study emphasizes that, beyond individual immunity, the duration of herd immunity constitutes the principal determinant of epidemic occurrence. Future public health planning must integrate surveillance (notably ambulatory), vaccination, and adaptive strategies to mitigate consequences after future epidemic risks.

ACKNOWLEDGMENTS

We thank the participants for their participation in this study.

We are grateful to the investigators of the PARI study Network: Drs Achkar M., Akou’Ou M-H., Ambacher Bensoussan C., Andre J-M., Ansoborlo -S., Antoine-Milhomme C., Auvrignon A., Bakhache P., Barrois S., Bastero R., Batard C., Bazouzi S., Beaufils-Philippe F., Beaussac B., Beguin A., Bellemin K., Bellulo S., Benani M., Berquier J., Blanc B., Blanc J-P., Blasquez A., Bled J., Bonniaud-Blot P., Bordes C., Boulanger S., Brancato S., Bresson O., Brigot D., Burtscher A., Cahn-Sellem F., Cambier Nappo E., Chaix J., Chartier Albrech C., Chatue Kamga H., Cheve A., Chollet A-C., Cocatrix F., Cohen R., Condor R., Coudy C., Courtot H., D Acremont G., D’Ovidio N., Dagrenat V., Dauriac A., De Brito B., Deberdt P., Defives i., Degand P., Delavie N., Delaygue C., Delobbe J-F., Delvaux S., Desandes R., Desvignes V., Deville M., Devulder C., Dubreuil B., Duchene S., Duhamel A., Dulorme F., Dumortier B., Durantel B., Elbez A., Fayech C., Frachette C., Galula L., Garraffo A., Gebhard F., Gelbert N., Geneste P., Genix M., Givois A., Goehringer F., Gorde-Grosjean S., Goulamhoussen S., Grue P., Gruniaux Wild É., Guiheneuf C., Hassid F., Hautefeuille C., Hennequin S., Houeto N., Hourlier D., Hubinois S., Issert É., Jayet D., Joseph M-G., Jouck E., Jouty C., Kampf Maupu F., Kerdudo-Veau C., Kherbaoui L., Kochert F., Koskas M., Laborde S., Lambert A-L., Lambert M., Langlais S., Le Gac I., Le Mouel F., Lecaillier F., Lecorche B., Legras C., Lemaitre C., Lemaitre D., Lemarie D., Leyronnas S., Lienhardt J-F., Loe-Loumou C., Louvel M., Lubelski P., Magagi J., Mamoudjy N., Manent Sellier D., Manet A., Marian I., Marret C., Marszal K., Masse M., Masserot C., Mawas c., Mercier A., Mercier A., Mercier-Oger M-O., Michot-Cottias A-S., Milliard D., Mindreau M., Minette D., Moore Wipf S., Nemesin B., Nold B., Nzunga N., Pailhous S., Pallard-Duhaut C., Paratte F., Perier A-C., Petit C., Pflieger H., Picard K., Piegay Broglia I., Pinard O., Pincant B., Plouhinec C., Pressac I., Pruvost Dussart I., Ravilly S., Roques G., Roudil P., Roussel P., Roy E., Salaun J-F., Salinier C., Salomez S., Sangenis M-I., Sarreau C., Sartelet I., Savajols E., Schlemmer C., Sellam A., Seris L., Seror E., Somerville D., Streicher M-P., Thiebault G., Thollot F., Tizi Oualou L., Touet V., Tourneur F., Traimond N., Treppoz S., Truffinet O., Vagnon B., Vasse C., Vaucan Gitto E., Vergnes C., Vernoux S., Vie Le Sage F., Vigreux j-c., Virey B., Werner A., Wollner A., Yako E., Zillmer S., Zouari M., Zrek-Mansour R.We are grateful to the ACTIV team: Ramay I, Servera M, Flores M, Destel I, Prieur A; Chalte J.

We are grateful to the CompuGroup Medical France team.