Increased risk of rhinovirus infection in children during the coronavirus disease‐19 pandemic

Abstract Background Coronavirus disease (COVID‐19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), was first detected in Japan in January 2020 and has spread throughout the country. Previous studies have reported that viral interference among influenza virus, rhinovirus, and other respiratory viruses can affect viral infections at the host and population level. Methods To investigate the impact of COVID‐19 on influenza and other respiratory virus infections, we analyzed clinical specimens collected from 2244 patients in Japan with respiratory diseases between January 2018 and September 2020. Results The frequency of influenza and other respiratory viruses (coxsackievirus A and B; echovirus; enterovirus; human coronavirus 229E, HKU1, NL63, and OC43; human metapneumovirus; human parainfluenza virus 1, 2, 3, and 4; human parechovirus; human respiratory syncytial virus; human adenovirus; human bocavirus; human parvovirus B19; herpes simplex virus type 1; and varicella‐zoster virus) was appreciably reduced among all patients during the COVID‐19 pandemic except for that of rhinovirus in children younger than 10 years, which was appreciably increased. COVID‐19 has not spread among this age group, suggesting an increased risk of rhinovirus infection in children. Conclusions Rhinovirus infections should be continuously monitored to understand their increased risk during the COVID‐19 pandemic and viral interference with SARS‐CoV‐2.


| INTRODUC TI ON
In Japan, coronavirus disease (COVID- 19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in January 2020 and has spread throughout the country.
With the COVID-19 pandemic still ongoing, the annual season of influenza and other respiratory virus epidemics has arrived. Previous studies have reported that viral interference among influenza virus, rhinovirus, and other respiratory viruses can affect viral infections at the host and population level. 1,2 To investigate the effect of COVID-19 on these virus infections, we analyzed clinical specimens collected from patients in Japan with respiratory diseases from January 2018 through September 2020.

| Clinical specimens
Respiratory specimens (nasal swab, throat swab, nasal discharge, saliva, tracheal aspiration fluid, or sputum) were collected from 2244 patients with respiratory diseases in Yokohama, Japan, from January 2018 through September 2020 as part of the National Epidemiological Surveillance of Infectious Diseases and the Active Epidemiological Investigation for COVID-19 in Japan. Of these 2244 patients, 1197 (53.3%) were men, 1044 (46.5%) were women, and 3 (0.1%) provided no sex information; 1119 (49.9%) were younger than 10 years, 1105 (49.2%) were aged 10 years or older, and 20 (0.9%) provided no age information. Specimens were negative for SARS-CoV-2.

| RE SULTS
Of the 2244 specimens, 592 influenza virus, 155 rhinovirus, and 475 other respiratory viruses were detected. Two or three viruses were co-detected in 61 specimens. Virus-specific seasonality was observed for influenza virus, rhinovirus, and other respiratory viruses as previously reported 2 ( Figure 1, Table S1). Influenza virus peaked in winter, whereas rhinovirus and the other respiratory viruses peaked in spring and autumn. After the first case of COVID-19 in Yokohama was detected in February 2020, the frequency of influenza and other respiratory viruses was appreciably reduced. In contrast, the frequency of rhinovirus infection increased appreciably during the COVID-19 pandemic. A study in Australia has also reported a high incidence of rhinovirus infection during the COVID-19 pandemic. 11 Next, we compared the frequency of five representative respiratory viruses by year to examine whether the frequency of these viruses increased during the COVID-19 pandemic (Figure 2). The representative viruses-coxsackievirus A and B; human metapneumovirus; human parainfluenza virus 1, 2, 3, and 4; human respiratory syncytial virus; and human adenovirus-were detected in more than 50 patients during the study period, and their maximum frequency per month was >10%. The frequency of these viruses was appreciably reduced after the COVID-19 pandemic began. These data show that the emergence of SARS-CoV-2 is inversely correlated with the number of patients with other respiratory virus infections.

SARS-CoV-2 infections have been less frequent in children than
in adults worldwide, including Yokohama, since the first case was detected. We compared the frequency of influenza virus and rhinovirus between children <10 years of age and patients aged 10 years or older (Figure 3, Table S1). The frequency of influenza virus was appreciably reduced in both age groups after the COVID-19 pandemic began. However, the frequency of rhinovirus increased appreciably during the COVID-19 pandemic in children <10 years of age but not in patients aged 10 years or older. Although COVID-19 has not spread among children, there is an increased risk of rhinovirus infection in children. Our results suggest an increased risk of rhinovirus infection in children. Rhinovirus causes the common cold but can also cause severe respiratory tract infection, which may be followed by pulmonary and extrapulmonary complications in some patients. 20 Previous studies reported that rhinovirus is more likely to cause severe disease in winter, although peak prevalence occurs in the spring and autumn. 21,22 Consequently, rhinovirus infections should be continuously monitored to understand their increased risk during the COVID-19 pandemic and viral interference with SARS-CoV-2.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that supports the findings of this study are available in the supplementary material of this article.