Conclusions
PHSMs to mitigate the COVID-19 pandemic have greatly impacted the epidemiology and evolution of respiratory viruses worldwide. This study aimed to investigate the impact of PHSMs on the genetic diversity of respiratory viruses detected in paediatric surveillance in Hong Kong from August 2020 to October 2021. The majority of HRV infections were type A, followed by C. HRV type B was rare, and the detection of other respiratory viruses was sporadic (Figure 1a ). Despite reduced circulation under strict PHSMs, the overall diversity of respiratory viruses increased, possibly due to changes in healthcare-seeking behaviour or heightened vigilance. As control measures were relaxed, HRV infections surged, similar to trends reported for RSV and influenza in other regions (27, 42).
Between the third and fourth waves of COVID-19 in Hong Kong, from September to November 2020, PHSMs were relaxed. During this time, Hong Kong saw a resurgence of HRV A cases predominated by A47 and A101 genotypes (41). These two genotypes were also reportedly predominant in Shanghai in 2020 (43). Strict containment measures applied during wave four caused a genetic bottleneck that eliminated three circulating lineages of A47 and A101. Though A47 and A101 were not subsequently detected in our study, a resurgence of genotype A49 occurred after face-to-face teaching resumed in March 2021 (Figure 1,3 ). During the summer of 2021, HRV cases again increased following the relaxation of PHSMs. Phylogenetic analysis indicates that the few A49 genotype viruses detected in September 2020 persisted between epidemic waves despite strict PHSMs to cause the March–July 2021 outbreak, which peaked in May.
In Hong Kong, the rise and fall of paediatric HRV cases were mainly associated with the suspension and resumption of face-to-face teaching (Figure 1 ). However, it is important to note that despite schools reopening, other PHSMs remained in place including mandatory face masks, reduced school hours, and socially-distanced seating (44). HRV cases rebounded as classes resumed despite social distancing precautions, whereas other respiratory viruses did not immediately return. Notably, it has previously been reported that face masks are not as effective in deflecting HRV in exhaled breath (45), and HRV has been found to remain stable on surfaces and exhibit resistance to ethanol and non-ionic detergents (46, 47). Taken together with the relatively less-conscientious hand hygiene of children, HRV may be less sensitive to COVID-19-related PMSHs.
Since the onset of the COVID-19 pandemic, HRV has been the second most widely reported respiratory virus, second only to SARS-CoV-2. Recent studies in the USA have shown that HRV continued to circulate throughout the COVID-19 pandemic (2), and despite enhanced hospital control and public health measures, cases continued to be identified at a higher than historical rate (48). Another study reported widespread and diverse HRV infections in homeless shelters, though no single genotype persisted for more than a few months (49). The cocirculation and alternate dominance of HRV A and C is consistent with studies in Hong Kong and around the world (4, 10, 43, 50, 51, 52, 53), and notably, a number of respiratory virus lineages, mostly HRV C, were detected through the end of our study.
While Hong Kong sequences within the same genotypes grouped together phylogenetically, some genotypes formed one or more clusters of their own within the group, which reveals the possibility of multiple transmission lineages and multiple introductions of the same genotype during the study period. Moreover, as COVID-19 drastically reduced international travel to and from Hong Kong during this study period, endemic circulation of these genotypes could not be ruled out. Other HRV genotypes sequenced in this study were genetically distinct from the limited number of available HRV sequences available in GenBank (Supplementary Tables 1-6). Analysis of these sequences was limited as some genotypes had less than 10 whole genomes available for comparison, and most sequences originated from USA.
HRV A49 and A47 were most frequently associated with URTI in this study, with 96% of A49 and 81% of A47 cases reporting respiratory symptoms and/or fever (Table 2). These genotypes are among those most associated with severe illness and hospitalization (3, 43). Although the small sample size precludes a clear correlation between the genotypes and clinical illness, these genotypes demonstrate epidemic potential and warrant further surveillance. While gastrointestinal symptoms were commonly observed among patients with HRV infections (Table 1), it should be noted that these samples were only screened for respiratory viruses, thus gastrointestinal symptoms could be attributable to coinfection with non-respiratory viruses or bacteria.
This study provides insights into the genetic diversity of HRV detected in paediatric cases hospitalized in Hong Kong during the COVID-19 pandemic. Despite reduced respiratory virus circulation, HRV remained prevalent, particularly HRV A and C. The implementation of PHSMs significantly affected the genetic diversity of HRV, as evidenced by the surge of A47 and A101 in November and A49 in May 2021 during relaxation of control measures. It is not clear if immunity towards HRV waned during this period, and although no correlation was found between HRV genotype and patient age, most symptomatic infections were caused by HRV A. These findings emphasize the importance of continued respiratory virus surveillance and HRV sequencing to improve our understanding of HRV transmission and inform effective public health measures.