The impact of non-pharmaceutical interventions on community non-SARS-CoV-2 respiratory infections in preschool children

Our results show that the COVID-19 pandemic-related NPI strongly reduced the number of self-reported ARI in healthy 3- and 4-year-old infants in Germany. NPI suppressed the spread of most seasonal viruses except HRV.

The observed reduction of ARI incidence during the NPI is in line with other studies focusing on the paediatric population in hospitals or using register data [8, 21, 22]. The reduction is likely to be caused by various NPI, although the impact of individual components is unclear. Respiratory infections, especially in early childhood, are very common and cause not just high socioeconomic burdens [23] but are also associated with the development of chronic diseases later in life [24]. However, fewer infections during NPI likely mean a reduced immunity afterwards. In some parts of the world, a strong atypical resurgence of respiratory infections, like RSV, was observed during summer months for children after easing NPI [25‐27]. The high proportion of susceptible individuals and the lack of exposure to certain viruses and bacteria could affect timing and severity of future ARI seasons [28].

We found that the prevalence of viral strains changed before and during NPI with suppression of severe viruses such as FluA + B, PIV1-4, RSV and MPV. The natural season period of some viruses was interrupted through the NPI. For example MPV, which is normally detected in late winter and spring [29], was no longer detectable during the pandemic period [30, 31]. However, some studies reported an off-season outbreak of MPV from May to July 2021 [32, 33]. Similarly, RSV, which mostly occurs between December to March each year [29], could rarely be found during the pandemic period [30, 34‐36]. Many hospitals, however, registered a massive off-season outbreak during summer months [27, 30, 34]. Interestingly, influenza virus infection incidence remained low during summer months [37, 38], this could indicate that climatic conditions and seasonality differentially affects the various viruses. In contrast, HRV was less affected by the NPI. HRV infections are highly common in children [39] and can cause light symptoms, which are usually associated with a common cold [40]. However, HRV can also cause severe symptoms leading to lower respiratory tract infections such as bronchitis [41]. In our study, HRV infections usually showed only mild symptoms.

Our findings from a population-based setting are in line with recent reports of registers or hospital data published in various countries which all describe that HRV circulation was unchanged during NPI to control the spread of SARS-CoV-2 [9, 13, 42, 43], but we also detected similar levels of AdV before and during the pandemic. This suggests that non-enveloped viruses were less affected by NPI. A major reason could be the stability of non-enveloped viruses, (e.g., HRV has been proven to be more resistant to detergents for hand washing [44] or disinfectants [45]). HRV and AdV are more effective than other airborne viruses at using the indirect transmission pathway (e.g. hand-to-hand contact followed by self-inoculation) [46‐48]. This might explain the high prevalence of HRV in children, as the hygiene behaviour is not yet well established [49]. However, we detected a strong decline in HEV, which also belongs to the non-enveloped viruses. Thus, a comprehensive explanation of our findings is still lacking, and further research is needed to better understand the circulation of enveloped and non-enveloped viruses during NPI. It has been also proposed that surgical masks might not prevent the transmission of HRV [50]. On the other hand, it was discussed that HRV might display some form of colonization and thus be present independently of infection symptoms [51, 52]. If HRV were part of the microbiome, then the fraction of symptomatic swabs without a responsible virus would substantially increase, particularly during the pandemic period when fewer co-detections were present. However, we detected HRV without co-detections in the symptomatic nasal swabs especially during the pandemic period, which points towards HRV being the causative virus in our samples. There is also the possibility that we detected different HRV species. There is evidence that HRV-A and HRV-C are frequently associated with more severe infections, while HRV-B is often associated with asymptomatic infections [53, 54]. However, we did not analyse the species.

The proportion of viral co-detections before the pandemic was surprisingly high compared to most previous studies where co-detection rates up to 40% [55, 56] were reported. However, most of those studies were conducted in hospital settings with severely infected children so that virus patterns might be altered compared to the LoewenKIDS’ community setting. In healthy children, higher co-detections may be normal; however, literature about co-detection in community settings is very limited. An explanation for co-detection could be that some viral shedding is prolonged although the infection already passed. It was also shown that some viruses (e.g., HRV) are able to colonise the nasal microbiome and are therefore non-pathogenic [51, 52]. During the pandemic period, viral co-detection was markedly reduced, which reflects the decline of most viruses.

A recent systematic review and meta-analysis showed that viral co-detections in children do not have an impact on the severity of the disease, where mostly hospital-based studies with clinical outcomes were included [57]. In our analysis, we also did not observe any change in severity of symptoms.

The bacterial presence was not affected by NPI, which is supported by findings for pneumococcal carriage [58, 59]. Detection of viral and bacterial strains in the same sample was rather common, and among them, almost all samples yielded bacterial co-detections with SP and HI. Asymptomatic nasopharyngeal carriage in healthy preschool children has been documented, 64% for HI [60] and at least 50% for SP [61], meaning that children are mostly colonised with those acting commensals after entering daycare [62]. Most of the children in our cohort entered day care in the second year of life [19] potentially explaining the high prevalence of HI and SP in our samples.