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.