key: cord-0950588-9jg9kr7f authors: Ye, Qing; Wang, Dongjie title: Epidemiological changes of common respiratory viruses in children during the COVID‐19 pandemic date: 2022-01-11 journal: J Med Virol DOI: 10.1002/jmv.27570 sha: 74e0569fdb4f653595f070a3d39a776e99cf14b0 doc_id: 950588 cord_uid: 9jg9kr7f A variety of non‐pharmaceutical interventions (NPIs) have been implemented to control the transmission of COVID‐19 in China. The effect of NPIs on other common respiratory viruses in children of different age groups has not been examined thus far. Respiratory specimens of children were collected to detect common childhood respiratory viruses, including influenza A (FluA), influenza B (FluB), adenovirus, and respiratory syncytial virus (RSV), at the Children's Hospital of Zhejiang University School of Medicine from January 1, 2019 to December 31, 2020. The epidemiological characteristics of the respiratory viruses in 2020 were compared with those in 2019. From January 2019 to December 2020, 165 622 specimens were collected. The proportion of infants aged 0−28 days (683, 2.24% vs. 1295, 0.96%, p = 0.000) and 1−12 months (8560, 28.12% vs. 20 875, 15.43%, p = 0.000) in 2020 increased significantly compared with that in 2019. There were two obvious increases in April and September in the number of specimens in children aged 4−6 years and >7 years. FluA, FluB, and RSV's age distribution patterns were surprisingly consistent with each other in 2020, and the positive rates of children aged 1−12 months were the highest in all age groups (FluA: 4.45%, FluB: 3.30%, RSV: 7.35%). Our study further confirms that the NPIs significantly decreased the transmission of common childhood respiratory viruses. The change in circulation characteristics of common respiratory viruses of children in different age groups varied. Therefore, we recommend that different protection strategies should be introduced for children of different age groups. Data from several studies suggest that the NPIs result in an overall decrease in the transmission of respiratory viruses. [10] [11] [12] [13] [14] In some periods after the epidemic, compared to previous years, the Global Influenza Surveillance, and Response System even reported a 99% reduction in the number of influenza-positive cases. 15 However, recent evidence suggests that some other respiratory viruses showed a propensity to reemerge. 16 Although some studies have reported the impact of the pandemic on the prevalence of respiratory viruses in children, [17] [18] [19] [20] few studies have focused on the influence of the NPIs on the circulation of common respiratory viruses in children of different age groups. Therefore, our study was conducted to report, and discuss the change in the epidemiological characteristics of common respiratory viruses in children of different ages under the COVID-19 pandemic and provide support for finding better protection strategies. All patients who met the criteria were continuously recruited at the Children's Hospital of Zhejiang University School of Medicine from January 1, 2019 to December 31, 2020 to evaluate the impact of the pandemic on the prevalence of common respiratory viruses in children. The inclusion criteria were (1) patients under 18 years old; (2) diagnosed with an acute respiratory infection (presenting with one or more of the following symptoms: fever, cough, earache, nasal congestion, rhinorrhea, sore throat, vomiting after coughing, wheezing, and labored, rapid, or shallow breathing). 21 Children infected with COVID-19 were excluded from the study. For each patient, during one course of illness, only the results of the first specimen were collected and analyzed. Respiratory specimens (nasopharyngeal aspirates/bronchoalveolar lavage fluid) were collected and handled by trained staff. The Respiratory Virus Antigen Detection Kit (Genesis) was used to detect respiratory viruses, including ADV, FluA, FluB, and RSV. After the specimens were delivered to the laboratory, they were handled according to a standard procedure. The specimens were first added to the sample extraction solution in the sampling tube and stirred. One hundred microliters of liquid in the tube were dropped onto the detection plate. After 15 min, the results could be observed according to the bands shown on the detection plate. The ages of the patients were expressed as medians and interquartile ranges, as they were not normally distributed. When comparing the distribution of respiratory viruses in different age groups in 2019 and 2020, the patients were divided into five age groups, including 0−28 days, 1−12 months, 1−3 years, 4−6 years, and older than 7 years. χ 2 tests and rank-sum tests were used when making comparisons between respective groups. A p value below 0.05 was considered to indicate a statistically significant difference. We performed statistical analysis with SPSS version 24.0. (Table 1) . For mixed viral infection, we found that most types of double infection in 2020 were significantly less frequent than those in 2019. Specifically, the positive rate of "ADV + FluA" dropped from 7.10‰ to 0.49‰ (p = 0.000), "ADV + FluB" from 2.62‰ to 0.26‰ (p = 0.000), "ADV + RSV" from 1.46‰ to 0.49‰ (p = 0.002), "FluA + RSV" from 0.51‰ to 0.09‰ (p = 0.000), and "FluA + FluB" from 0.01‰ to 0.0‰ (p = 0.000). Furthermore, there were no triple or quadruple infections in 2020, yet in 2019, the number of specimens detected was 15 and 3, respectively ( Figure 1 ). We observed that ADV was detected throughout 2019 with a higher prevalence in the first half-year, whereas the phenomenon was not December 2019: 4.81%, Figure 2D ). In 2020, there was a sharp drop in the number of specimens in all age groups after January 2020. Moreover, there were two apparent increases in April and September in the number of specimens of children aged 4−6 years and >7 years ( Figure 3D,E) . For children aged 1−3 years, a noticeable increase in specimen number in April and a slight increase in November can be observed ( Figure 3C ). This trend can also be seen in children aged 1−28 days and 1−12 months, but it was not evident ( Figure 3A,B) . In other words, the typical seasonal distribution pattern in different age groups in 2019 no longer existed in 2020. The practice of postpartum confinement may partially explain why the same thing did not go for infants aged 0−28 days. In China, after a woman gives birth to a baby during the first month, the mother and the baby are supposed to stay at home and avoid contact with other people. Therefore, more attention should be given to children aged 1−12 months in China to prevent infection by respiratory viruses. We observed that RSV became the most common virus in 2020 instead of ADV and FluA in 2019. In addition, the seasonal distribution patterns of FluA and FluB almost disappeared since China initiated the emergency response, while the seasonality of RSV remained as it still peaked in the winter months. However, to the best of our knowledge, the mechanism that accounts for this phenomenon remains unclear. One possible reason is the relationship between RSV and the influenza virus. It has been reported that a localized inflammatory response could be induced after infection with the influenza virus, which can limit the replication and spread of RSV. 23, 24 This interaction was greatly weakened, as the circulation of the influenza virus in 2020 was rarely low, which may partially offset the influence brought by public health measures. This trend of RSV is likely to continue as the reemergence of RSV was also reported in some other areas. [25] [26] [27] Moreover, an outbreak of RSV is predicted by the regression model in Japan after the COVID-19 pandemic. 28 Therefore, we speculate that RSV could be the predominant respiratory virus and should be monitored more diligently in children in the future. We also found that the change in seasonality of respiratory viruses in different age groups varied. For children aged 4−6 years and more than 7 years, in April and September in 2020, an increase in the number of specimens can be observed, which is different from that in 2019. We attribute this change to increasing social contact since the timing is highly consistent with reopening schools and kindergartens. We consider this trend to continue with the relaxation of COVID-19 mitigation measures and the reopening of shops and workplaces. Moreover, according to recent research, more intense epidemics could occur after the low incidence of the influenza virus due to a drop in herd immunity. 29 Hence, children older than 3 years need to enhance public health measures such as social distancing and personal hygiene after the reopening of the school and kindergarten. F I G U R E 3 Number of respiratory virus specimens detected in different age groups according to months in 2020 (red) compared with 2019 (blue). The patients were divided into five age groups, including 0−28 days (A), 1−12 months (B), 1−3 years (C), 4−6 years (D), and older than 7 years (E). The red block represents the period from the level-1 emergency response initiated in January 2020 to the emergency response adjusted to level 3 in April 2020 in Zhejiang, China. The yellow block represents the period from emergency response adjusted to level 3 to school reopening in May 2020 in Zhejiang, China Our research may have some limitations. All the data were obtained from one hospital to introduce selection bias. Data acquired from different places will be more convincing. The other main limitation of the study is that only four types of common respiratory viruses are covered in this study. Limited by the hospital's testing program, other common respiratory viruses, such as rhinovirus and parainfluenza virus, were not covered. 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Vaccines Epidemiological changes of common respiratory viruses in children during the COVID-19 pandemic