This molecular-based regional surveillance for viral ARIs was designed to address several limitations of the current surveillance, NESID. First, the spectrum of pathogens (only SARS-CoV-2/Flu/RSV) in the NESID is limited. Second, sampling and reporting biases are present. The participating sites are concentrated in pediatric clinics. In particular, RSV cases have been limited to children. Cases are determined at the clinician’s discretion without defined criteria, and microbiological diagnosis is mostly dependent on rapid antigen tests. Third, only the mean number of cases per site without age information was reported, without denominators. In contrast, our surveillance targets a broader spectrum of pathogens from all age groups and can generate age-stratified positive sample counts and rates. Our laboratory-based surveillance performed centralized molecular testing, which can provide highly accurate detection of pathogens compared with rapid antigen tests at each site. The collected clinical samples can also be used for further testing (e.g., genomic analysis and viral culture) and research.
According to our surveillance program, we estimated the prevalence of viral ARIs for each age group. The detection rates of respiratory viruses, except for that of metapneumovirus, significantly varied according to age group (Fig. 2). These results are concordant with those of previous studies that reported different prevalences of pathogens according to age, period, and region14,15,16. The discrepancies in the monthly trends and the number of cases or positive samples between the NESID and our data (Fig. 3) can be largely explained by the sampling bias of NESID toward children, although differences in the sampling sites might also have affected the data. These observations confirmed the importance of age-stratified local surveillance.
The viruses detected in this study are all considered causes of hospital admission17 and pneumonia18,19. Among these, SARS-CoV-2/Flu/RSV are especially important because of their prevalence and the availability of vaccines and therapeutics. Following recent approval of vaccines for elderly individuals and maternal immunization20, our surveillance provides valuable data regarding adult RSV infections. Data for viruses other than SARS-CoV-2/Flu/RSV are of public health importance because these viruses can cause endemics14,15,16,17 and outbreaks within facilities21,22. Previous reports indicate that the detection of viruses other than SARS-CoV-2/Flu/RSV has led to the identification of causative organisms in ARI outbreaks due to unknown etiology, the initiation and cessation of isolation and transmission-based precautions in outbreak settings or routine screening activities for symptomatic and asymptomatic admissions, and the avoidance of mixing patients with different organisms11,21,22,23,24,25. In a clinical setting, the detection of these viruses may facilitate subsequent modifications of empiric broad-spectrum antimicrobials, even in the absence of specific interventions.
There are no surveillance systems that target a broad range of respiratory viruses in Japan. Only several retrospective studies from a single institution using FilmArray tests have been reported. One study conducted in Yamanashi that compared the COVID-19 pandemic and post-COVID-19 (May–September 2023) periods revealed an increase in overall pathogen detection rates (specifically, metapneumovirus, rhinovirus/enterovirus, and RSV) in all age groups15. In children ≤ 10 years old, the positivity rates of adenovirus, Bordetella pertussis, and parainfluenza viruses 2 and 4 also increased, whereas the positivity rates of SARS-CoV-2, seasonal coronaviruses HKU1 and OC43, and parainfluenza virus 1 decreased. During the COVID-19 pandemic (2022–2022), a study in Nara detected a higher positivity rate for rhinovirus/enterovirus than SARS-CoV-2 throughout most of the study period and peaks of RSV and parainfluenza virus 3 detection in the summer of 202116. A large-scale study that examined > 50,000 samples obtained from inpatients or children for whom admission was planned in the USA reported the resurgence of viruses other than SARS-CoV-2 during 202217. Among pediatric patients aged < 18 years, rhinovirus/enterovirus had the highest incidence in almost all months, with distinct seasonal increases in the incidence of different viruses in the following order: seasonal coronavirus, influenza virus, metapneumovirus, parainfluenza virus, and RSV. Our results indicate that viruses other than SARS-CoV-2/Flu/RSV cause ARIs more frequently. Rhinovirus/enterovirus was the most prevalently detected in the < 6 year age group; seasonal coronavirus and rhinovirus/enterovirus were more prevalent than SARS-CoV-2 and influenza virus were in the 6–17 year age group; and seasonal coronavirus was more prevalent than influenza virus was in the ≥ 18 year age group. These epidemiological data highlight the importance of a real-time local surveillance program with molecular diagnostics that cover a broad range of viruses.
Multiplexed pathogen detection assays can detect viral coinfections14,26. A recent study in the USA revealed that viral coinfection occurred more frequently in children (21% vs. 4% in those < 18 and ≥ 18 years, respectively), and coinfection rates were much lower than expected on the basis of the incidence of each virus, suggesting the presence of viral exclusionary effects17. Our data also revealed a relatively high rate of multiple viruses in children, which was in line with these observations.
This study has several limitations. We probably underestimated the detection rates of viruses other than SARS-CoV-2/Flu/RSV because of the presence of coinfections in SARS-CoV-2/Flu/RSV-positive samples. This bias may not have a large impact because SARS-CoV-2, influenza virus, and RSV are associated with the lowest probability of coinfection17. Sampling bias could be present due to the relatively low numbers of participating facilities and samples from children and the use of a random sampling strategy for FilmArray testing. Notably, this surveillance is based on the test positivity of symptomatic patients and may include recovered patients with prolonged viral shedding from prior infection episodes.
We demonstrated the differences in the detection rates and trends of respiratory viruses among age groups using the developed local molecular surveillance program. This surveillance is unique in terms of age stratification, the molecular detection basis for SARS-CoV-2/Flu/RSV, and the inclusion of a broad range of viruses. Our data will help accurately elucidate the epidemiology of viral ARIs at different ages and may help clinicians and public health professionals plan infection control and prevention strategies. Further detailed analysis, including viral genomics, will enhance our knowledge of the spread of respiratory viruses.
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