key: cord-0695102-eghrwdao
authors: Hsu, Hao-Ting; Huang, Fang-Liang; Ting, Pei-Ju; Chang, Chun-Chih; Chen, Po-Yen
title: The Epidemiological Features of Pediatric Viral Respiratory Infection During the COVID-19 Pandemic in Taiwan
date: 2021-10-09
journal: J Microbiol Immunol Infect
DOI: 10.1016/j.jmii.2021.09.017
sha: a2063c99f82870c82332d7a882b1e48c65f1a1ba
doc_id: 695102
cord_uid: eghrwdao

Background Enhanced nonpharmaceutical interventions (NPIs) to prevent the Coronavirus Disease 2019 (COVID-19) have shown various levels of impact on common respiratory pathogens. We aimed to analyze the epidemiological changes seen in certain common respiratory viruses found in Taiwanese children (e.g., influenza virus, enterovirus, parainfluenza virus, adenovirus and respiratory syncytial virus (RSV)) after the implementation of public health measures, as well as interpret the possible meaning of these changes. Methods This retrospective observational study examined the viral isolation from children younger than 18 years at a medical center in central Taiwan during the period January 2015 – December 2020, a time frame of six years. Viral isolations prior to the COVID-19 pandemic (January 2015 – December 2019), along with those during the post-COVID-19 period (January – December 2020) were analyzed and compared. Results A total of 6,899 throat swab samples were collected during the pre-pandemic period of 2015 to 2019, with 2,681 of them having a positive result (38.86%). There were a total of 713 samples collected in 2020, with 142 of them showing positive results (19.92%). The overall positive rate of viral isolates significantly decreased in 2020 (p < 0.001). Declines in the isolation of the influenza virus, parainfluenza virus, adenovirus and enterovirus were observed. The RSV surprisingly became the leading isolate, with up to 47 (6.59%) instances in 2020, and showing an unusual peak in the winter of 2020. The rise began in September of 2020 and reached its plateau in November of that year. Conclusions Most respiratory viruses decreased under NPIs regarding SARS-CoV-2. However, the RSV outbreak in the winter of 2020 had shown the limitation of current NPIs. Possible explanations have been discussed in details and public preventive measures should be reinforced for RSV, particularly amongst people having young children both at home and in care centers.

The Coronavirus Disease 2019 (COVID- 19) pandemic has changed the way of life in almost 2 every country on the planet. Prior to vaccines and effective antivirals becoming available, 3 nonpharmaceutical interventions (NPIs) had been the most effective available form of control both 4 locally and globally, as well as for the mitigation of COVID-19 (1). These NPIs, including social 5 distancing policies, the wearing of face masks, hand sanitation, lockdowns of certain scales in 6 administrative districts, and travel restrictions, all provided a temporary containment of 7 COVID-19 in several countries. There were many NPIs implemented in Taiwan in the year 2020. 8

Individuals had to wear face masks in indoor public spaces, on public transportation and in 9 healthcare facilities. Social distancing was also strictly required in populated public spaces. 10

International border control was carried out through the requirement that all arriving passengers 11 undergo a 14-day quarantine period, with active surveillance on body temperature and respiratory 12 symptoms also being implemented . 13 Surveillance studies had previously demonstrated the potential benefits of NPIs on preventing 14 the transmission of several common pathogens via the respiratory route (2). Surveillance data 15 taken in 2020 from Korea and Japan showed a decrease in influenza activity as compared with 16 previous seasons (3, 4). Studies from France, Finland, and rural Alaska had also shown decreases 17 in most acute respiratory infections in children (5-7). A significant reduction in hospital admissions 18 for both non-influenza respiratory viruses and influenza was reported in Singapore (8). Systematic 19 reviews have also considered the reduction of transmission associated with mask wearing for 20 respiratory viruses (9, 10). A Taiwan study in 2020 using figures taken from the National Health 21

Insurance Research Database (NHIRD) showed significantly lower rates of common infections after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) preventive measures 23 were announced (11). A recent study in northern Taiwan using multiplex RT-PCR tests also 24 showed a reduced average positivity rate of 11.2% in respiratory viruses after nationwide public health interventions were established (12). 1 Despite many studies having had already revealed similar findings, the methods of population 2 selection varied from study to study. The various study samples may have come from a database 3 bank using codes of diagnosis, multiplex RT-PCR tests, viral cultures, serum tests and also various 4 kinds of rapid antigen tests. Diagnoses may have been made clinically without microbiological 5 evidence. Serum tests and rapid antigen tests cannot completely reflect true infections in time, 6 while multiplex PCR is a relatively novel technique with limited universality. Amongst these 7 methods, it is viral cultures which may provide consistent data homogeneity for longer periods of 8

We aimed to analyze the epidemiological changes in some common respiratory viral 10 pathogens found in Taiwan after the application of public health measures, as well as interpret the 11 possible meaning of these changes. collected. The RSV rapid antigen test using the BinaxNOW RSV card (Abbott Diagnostics 10 Scarborough, Inc., ME, US), with 89% sensitivity and 100% specificity according to the product 11 instructions, was processed at the laboratory of the Children's Medical Center of Taichung 12

Veterans General Hospital. The use of these data involving human subjects was appropriately Hypothesis testing using the Chi-square test was performed to assess differences between the 2 number of detected viruses in the 2 groups (i.e., 2015-2019 and 2020). A p value <0.05 was 3 considered statistically significant. Analysis was performed using IBM SPSS Statistics, Version while the peak positive rate was in July, 2019 (55.56%). In 2020, the most prevalent month was 16

December, while the highest positive rate was in November (44.9%). The six-year trend for these 17 five viruses is shown in Figure 3 . We also collected the RSV isolation numbers from children 18 under six years of age from the Epidemic Intelligence Center for comparison, revealing a sudden 19 rise since the 43th week, which was the fourth week in October of 2020. declined, as we can see from the CDC surveillance system (13) . In our study however, a decline 16

was not observed in all the selected pathogens. 17

In a pediatric population, viral spread by an asymptomatic adult carrier remains an important 18

factor. It had been demonstrated that an asymptomatic individual may shed the influenza virus, 19

although studies have not conclusively determined if such people will effectively transmit 20 influenza (14) . Influenza virus transmission may be reduced through NPIs, particularly by 21 following proper hand hygiene protocol and the wearing of face masks (15, 16). Other viruses e.g., 22

adenovirus, RSV, parainfluenza virus and enterovirus are usually carried by an asymptomatic 23

individual (17) (18) (19) . This phenomenon implies that there are differences in the natural reservoirs of surrounding the public measures e.g., face mask wearing and hand sanitation can be expected, as 3 most people tend to take off their face masks and perform hand hygiene less often at home. This 4 situation is particularly prominent for those people having infants and toddlers. Therefore, due to 5 personal hygiene habits and close physical contact with these young individuals, the spread of 6 these viruses will facilitate. Also, it has been proven that asymptomatic carriers excreting the 7 enterovirus play a crucial role in the spread of hand-foot-mouth disease, with their "silent" 8 presence helping to perpetuate enterovirus circulation in their community (20). The spread of the 9 enterovirus is often seen amongst children having frequent and close contact in schools and child 10 care centers. Social distancing contributes to a decline in its prevalence, as observed in our study. 11

A decrease in visits to hospitals and local clinics also reduces any contact with other infected 12

An unexpected outbreak of bronchiolitis amongst children occurred from September 2020 to 14

December 2020 in our hospital. A similar finding from the contract virological laboratory of 15 Taiwan's CDC has shown a high rate of RSV isolation since September 2020. A study performed 16 in Australia showed a significant reduction in RSV detection and admissions, emergency 17 department visits and intensive care unit admissions due to acute bronchiolitis in New South Wales 18 during the winter of 2020 (21). This was quite a different finding when compared with our study. 19

Also, a study in Singapore also showed an overall decrease in RSV incidence in 2020, as 20 compared with 2019 (22). These differences could be attributed to climate, culture, quarantine 21 methods, personal protective equipment, hygiene and habits. 22

RSV infection is mainly presented as bronchiolitis in children younger than 3 years of age, 23 causing endemics during the fall and winter seasons in temperate countries, as well as during the 24 hot rainy seasons in tropical climates. A biennial pattern with hospitalization peaks in spring and 25 fall due to RSV bronchiolitis in Taiwan had been reported in 2011, even though there is no 1 significant seasonality in southern Taiwan (23). We also found that there was a seasonality of RSV 2 bronchiolitis occurring during the period 2015-2020 (Figure 3) . The peak season for RSV infection 3 is summer, with a usual decline being seen in winter, except in 2020 during the COVID- 19 4 pandemic. Taichung is a city located in central Taiwan with a warm, humid subtropical climate. 5

The rainy season is mostly during May-August, which corresponds to the epidemiological findings 6 seen in tropical areas (24-26). These findings indicate there was a distinct rise in RSV incidence in 7 the winter of 2020, despite the public preventive measures of COVID-19 having been 8 implemented. Other than the asymptomatic carriage reasoning, a possible explanation could be the 9 decreased prevalence of co-infections with other respiratory pathogens. In a Dutch 10 community-based study, viral load was significantly associated with disease severity when RSV 11 was the only pathogen detected, although there was no evident association seen in infants 12 co-infected with RSV and another respiratory virus (27). The decreased incidence of other 13 respiratory viruses may be attributed to an increased incidence of RSV being isolated on its own, 14 which caused more patients to have severe symptoms. This may explain the phenomenon we 15 observed in the winter of 2020. Another possible explanation is age-related. Family exposure 16 usually occurs through an infected school age child, whom the parents believe has only a mild 17 "cold". Subsequently, other young children in the family then become secondarily infected. 

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