We thank dr. Lear, dr. Sriskandan and dr. Parks for their thoughtful comments1 on our study and for highlighting several important considerations when interpreting ecological analyses of viral activity and invasive Streptococcus pyogenes (iGAS) incidence and welcome the opportunity to clarify several methodological points.
First, differences in surveillance systems and diagnostic practices across countries are an acknowledged limitation. However, only a very small number of sites and samples used molecular or antigen-based methods; culture-based confirmation was overwhelmingly predominant. Importantly, the case definition—GAS isolated from a sterile site—was consistent across all countries, allowing meaningful comparison of trends.2 While increased PCR use may have influenced detection slightly, it is unlikely to explain the magnitude or timing of the observed variations.
Regarding the use of Google Trends data, we acknowledge that this approach is less traditional in infectious disease epidemiology, but it is supported by several published analyses using Google Trends topics as proxies for RSV, influenza, and varicella-zoster virus.3, 4, 5
Moreover, the PopHive platform developed by the Yale School of Public Health demonstrates its application in real-time RSV monitoring.
Bronchiolitis indeed predominantly occurs in infants and young children and the majority of cases are caused by RSV; the clinical relevance of this condition is therefore greatest in this population.4,6,7 However, RSV's seasonal peak, mirrors respiratory infections across all paediatric age groups.6 Furthermore, Crowson et al. included older children in their Google Trends study, supporting its applicability beyond infancy.4 Additionally, bronchiolitis is a well-established proxy for RSV in ICD-10–based studies.7
Importantly, we found strong correlations between Google Trends and national viral surveillance data, supporting the validity of this approach.2 While digital search data cannot replace laboratory systems, it can serve as a valuable complementary tool where traditional surveillance is limited.
Second, we agree that population-level shifts in immunity after the COVID-19 pandemic represent a relevant confounder. The important recent work by Dokal et al. highlights that reduced viral and bacterial exposure during non-pharmaceutical interventions has led to reduced immunity to both RSV and S. pyogenes. While our approach could not adjust for individual-level immunity, these findings are consistent with our observations and demonstrate that epidemiological analyses and immunological evaluations provide complementary perspectives on the same phenomenon.
Naturally, we agree that correlation alone does not establish causation. Our findings do support the interpretation that both varicella and respiratory viruses helped shape disease patterns, as the unprecedented scale of the 2022–2023 winter peak closely coincided with viral circulation. It is very likely that this phenomenon is multifactorial, with multiple drivers contributing to the observed patterns.
To determine this more conclusively and disentangle the contribution of each driver, individual-level data with laboratory-confirmed pathogens are essential. Surveillance systems should therefore aim to integrate pathogen-specific data with detailed clinical phenotyping.
In summary, our analysis highlights temporal associations between viral activity and iGAS incidence during a major post-pandemic transition, while fully acknowledging the need for more granular data to explore causation. We welcome continued international collaboration to enhance surveillance and integrate clinical, microbiological, and population-level data to understand the drivers of the recent resurgence.
Contributors
All authors contributed substantially to the preparation of this response. DB drafted the initial version and all authors critically reviewed and refined the response letter. All authors reviewed the final version, approved its submission, and take full responsibility for the content of the reply.
Declaration of interests
NO declares receiving travel grants from Pfizer, Sanofi and MSD.
The authors declare no competing interests.
References
- 1.Lear R., Sriskandan S., Parks T. Viral infections and invasive group A streptococcal disease incidence during 2022-2023. Lancet Reg Health Eur. 2025 doi: 10.1016/j.lanepe.2025.101581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Lenglart L., Özmen I., Aguilera-Alonso D., Blazquez-Gamero D., Boeddha N.P., et al. Paediatric invasive group A streptococcal infections and associations with viral infections in 15 European countries after lifting non-pharmaceutical interventions against SARS-CoV-2: an interrupted time-series analysis. Lancet Reg Health Eur. 2025;59 doi: 10.1016/j.lanepe.2025.101497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Bakker K.M., Martinez-Bakker M.E., Helm B., Stevenson T.J. Digital epidemiology reveals global childhood disease seasonality and the effects of immunization. Proc Natl Acad Sci U S A. 2016;113:6689–6694. doi: 10.1073/pnas.1523941113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Crowson M.G., Witsell D., Eskander A. Using google trends to predict pediatric respiratory syncytial virus encounters at a major health care system. J Med Syst. 2020;44:57. doi: 10.1007/s10916-020-1526-8. [DOI] [PubMed] [Google Scholar]
- 5.Schneider P.P., van Gool C.J., Spreeuwenberg P., Hooiveld M., Donker G.A., et al. Using web search queries to monitor influenza-like illness: an exploratory retrospective analysis, Netherlands, 2017/18 influenza season. Euro Surveill. 2020;25 doi: 10.2807/1560-7917.ES.2020.25.21.1900221. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Guarnieri V., Macucci C., Mollo A., Trapani S., Moriondo M., et al. Impact of respiratory syncytial virus on older children: exploring the potential for preventive strategies beyond the age of 2 years. Vaccine. 2024;42 doi: 10.1016/j.vaccine.2024.126170. [DOI] [PubMed] [Google Scholar]
- 7.Johannesen C.K., van Wijhe M., Tong S., et al. Age-specific estimates of respiratory syncytial virus-associated hospitalizations in 6 European countries: a time series analysis. J Infect Dis. 2022;226:S29–S37. doi: 10.1093/infdis/jiac150. [DOI] [PubMed] [Google Scholar]