gao-et-al-2023-epidemiological-characteristics-of-respiratory-viruses-in-children-during-the-covid-19-epidemic-in
gao-et-al-2023-epidemiological-characteristics-of-respiratory-viruses-in-children-during-the-covid-19-epidemic-in
gao-et-al-2023-epidemiological-characteristics-of-respiratory-viruses-in-children-during-the-covid-19-epidemic-in
ABSTRACT The purpose of this retrospective study was to analyze the prevalence
of respiratory viruses among children with acute respiratory tract infections (ARTIs)
during the coronavirus disease 2019 epidemic (1 March 2020–28 February 2022). This
study investigated respiratory viral specimens from children with ARTIs. A total of 7,092
children (<14 years) with ARTIs were included in this study, with a boy-to-girl ratio of
1.43. The median age was 1 year and 5 months. The average age of the patients was 2.7
± 3.1 years. Patients < 3 years of age were the main population with ARTIs (67%). The
predominant viruses were respiratory syncytial virus (RSV) (10.1%) and influenza virus
(A and B 9.7%) during the 2 years of the pandemic (1 March 2020–28 February 2022).
The proportion of positive viral test results among patients with ARTIs < 6 years of age
was higher than that among patients with ARTIs aged 6–14 years (17.3% vs. 5.7%, P <
IMPORTANCE During the coronavirus disease 2019 epidemic, the Chinese govern
ment launched and used a series of nonpharmaceutical interventions (NPIs), includ
ing banning social gatherings, wearing face masks, home isolation, and maintaining
hand hygiene, to control the disease spread. Whether and how NPIs influence other
respiratory viruses in children remain unclear. In this article, we analyzed relative data
and found that the number of samples and positive proportion of respiratory viruses
decreased significantly compared with that before the epidemic. Clinicians and public
health policymakers should pay attention to changes in the epidemic trends and types Editor Tulip A. Jhaveri, University of Mississippi
of respiratory viruses and maintain monitoring of respiratory-related viruses to avoid Medical Center, Jackson, Mississippi, USA
possible abnormal rebounds and epidemic outbreaks of these viruses. Ad Hoc Peer Reviewer Nazly Shafagati, Quest
Diagnostics, Chantilly, Virginia, USA
KEYWORDS epidemiology, COVID-19, respiratory infection, virus Address correspondence to Lei-Wen Peng,
[email protected].
A cute respiratory tract infections (ARTIs) are the most common disease in children
and adults (1, 2). ARTIs can occur regardless of age, sex, season, and region and
are the main cause of infectious disease morbidity and mortality in China and world
The authors declare no conflict of interest.
wide (1, 2). Pathogens, including bacteria, mycoplasma, chlamydia, fungi and parasites, Received 22 June 2023
and viruses (such as influenza viruses, respiratory viruses, and rhinoviruses), have been Accepted 31 October 2023
Published 5 December 2023
identified as major causes of ARTIs in children (3–5). Studies have shown that acute
viral respiratory tract infection is the leading cause of hospitalization among infants and Copyright © 2023 Gao et al. This is an open-access
article distributed under the terms of the Creative
children in developed countries (6) and is the leading cause of death in developing
Commons Attribution 4.0 International license.
countries (7, 8). At present, respiratory tract viruses, including human parainfluenza virus,
respiratory syncytial virus (RSV), rhinovirus, coronavirus, adenovirus (ADV), and influenza
virus, are the most common pathogens associated with ARTIs in children (9). Relevant
studies have shown that controlling the spread of respiratory viruses is conducive to
the growth and development of children. Since the immune and respiratory systems of
infants and preschool children are not yet mature, early viral respiratory tract infections
may have an adverse effect on lung development and increase the risk of incident
asthma (10). ARTIs caused by viruses are the major cause of death and illness among
children under 5 years of age (11). Therefore, the prevalence of respiratory viruses that
cause ARTIs in children deserves our attention and continuous monitoring.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2). Since December 2019, COVID-19 has spread rapidly and
subsequently become a pandemic. The World Health Organization declared COVID-19
a public health emergency of international concern on 30 January 2020. To control the
spread of SARS-CoV-2, a series of nonpharmaceutical interventions (NPIs) were rapidly
launched and used to control the spread of the disease worldwide. The categories
of NPIs included banning social gatherings, wearing face masks, home isolation, and
maintaining hand hygiene, which played an important role in controlling the spread of
SARS-CoV-2 (12). By the end of March 2020, China had successfully controlled the first
wave of the COVID-19 epidemic peak (13). In addition, studies have shown that NPIs
affect the epidemic trends and transmission patterns of infectious diseases transmitted
by air or feces, such as the common cold, gastroenteritis, bronchiolitis, and acute otitis
media (14).
Our research group collected relevant data and analyzed the epidemiological
characteristics of ARTIs caused by respiratory viruses in children before the outbreak
ARTIs mentioned in the outpatient or discharge diagnosis. The exclusion criterion was
the lack of information on ARTIs in the top three outpatient or discharge diagnoses. All
patients were examined and diagnosed by clinicians.
Sample evaluation
Nasopharyngeal swabs were collected from patients (n = 7092) in the outpatient or
inpatient ward and sent to the hospital laboratory for testing. After receiving the
nasopharyngeal swabs, the laboratory technicians immediately processed and tested
the samples. Seven respiratory viruses, including RSV; influenza A and B; parainfluenza
viruses (PIV) I, II, and III; and ADV, were detected by a direct immunofluorescence assay
(Diagnostic Hybrids Inc., Athens, OH, USA) using nasopharyngeal swabs. The direct
immunofluorescence assay is relatively simple and inexpensive and is widely used in
clinical respiratory virus testing. Quality control will be performed in each test to ensure
that the results are reliable. At the same time, if the sample test results were suspicious,
they needed to be verified by PCR before inclusion in this study. The direct immunofluor
escence assay kit did not contain metapneumovirus; to ensure the consistency of the
results, there was no metapneumovirus testing. The clinician tested for metapneumovi
rus by PCR.
Data collection
The laboratory test results and patient demographic data (name, sex, age, clinical
diagnosis, and sampling time) were extracted from the laboratory information system
(LIS) of West China Second Hospital of Sichuan University. The study protocol was
approved by the Ethics Committee of West China Second University Hospital, Sichuan
University.
RESULTS
From 1 March 2020 to 28 February 2022, 7,092 patients who came to the hospital and
were diagnosed with ARTIs were included in this study. A total of 638 patients were
excluded. The sociodemographic variables associated with all samples are summarized
in Table 1. Regarding the age distribution of patients, patients aged 6 months to 3
years were the main population with ARTIs (35.3%), followed by patients aged 28 days
to 6 months (20.3%). The median age was 1 year and 5 months (range: 0 days to 14
years). The average age of the patients was 2.7 ± 3.1 years. Patients < 3 years of age
were the main population with ARTIs (67%). There were significantly more boys than
girls (58.9% vs. 41.1%, P < 0.01). The number of inpatients was significantly higher than
that of outpatients (61.2% vs. 38.8%, P < 0.01). However, the positive proportion of virus
detection among inpatients was significantly lower than that among outpatients (3.8%
vs. 19.3%, P < 0.01).
Regarding the prevalence of respiratory viruses among children with ARTIs, of the
7,092 patients, 1,635 patients (23.1%) had respiratory viruses. The positive proportions of
influenza A, influenza B, PIV I, PIV II, PIV III, ADV, and RSV were 4.1%, 5.6%, 0.7%, 0.1%,
1.1%, 1.3%, and 10.1%, respectively (Table 1). The predominant viruses were RSV (10.1%,
P < 0.01) and influenza (A and B 9.7%, P < 0.01) during the study period, followed by PIV
(I, II, and III, 1.9%) and ADV (1.3%). Among patients of different ages, the proportion of
positive viral test results among patients < 6 years of age was significantly higher than
that among patients aged 6–14 years (17.3% vs. 5.7%, P < 0.01). RSV infections were
more common among patients < 3 years of age (9.4%, 667/7,092, P < 0.001). The positive
proportion of influenza A among patients aged 3–6 years was significantly higher than
that of other viruses (P < 0.01). Influenza B infections were more common in patients
aged 6–14 years (P < 0.01) (Fig. S1). The positive proportion among boys was higher
than that among girls (14.4% vs. 8.6%, P < 0.01). The seasonal distribution of the sample
positive proportion during the study period is shown in Fig. 1. The positive proportions
of boys, girls, and total in the autumn and winter seasons were significantly higher than
those in the spring and summer seasons during the study period. In the first year, the
positive proportion of boys was highest in January (24.4%) and lowest in July (2.2%) (Fig.
FIG 1 Monthly activity patterns of the positive proportion of respiratory viruses. (A) Monthly activity patterns of the positive proportion of respiratory viruses
proportion of the other four viruses was low (Fig. 3B). Among all positive samples, 61.2%
came from boys and 38.9% came from girls (Fig. 3C). The main positive proportion of
virus detection among boys was RSV and influenza A and B, and the main positive
proportion of virus detection among girls was RSV and influenza A and B (Fig. 3D). A total
of 87.4% were outpatients and 12.6% were inpatients (Fig. 3E). Compared with the
previous year, there was no statistically significant difference in the proportion of boys
and girls or inpatients and outpatients (P > 0.05). The age distribution of positive patients
was as follows: most patients were 6–14 years old (n = 340), followed by 6 months to 3
years old (n = 246) and 28 days to 6 months old (n = 213) (Fig. 3F).
DISCUSSION
ARTIs account for a large proportion of infectious diseases in children, and respiratory
viruses are the most common cause of ARTIs in children and infants (15, 16). Although
the clinical characteristics of children and infants infected with different kinds of
respiratory viruses are different, their transmission routes are nearly the same, mainly
through droplets and aerosols and direct or indirect contact with infected secretions.
This study focused on the prevalence of respiratory virus infections in Southwest China
during the COVID-19 pandemic, aiming to investigate the impact of NPIs on the preva
lence of respiratory viruses among children and infants.
In this study, we first counted the number of children with ARTIs who were tested for
viral antigens during the COVID-19 pandemic. The total number of children tested was
7,092 from March 2020 to March 2022. Compared with the related data published by our
research group from March 2018 to March 2020, the number of patients decreased
substantially (7,092 vs. 11,813), and the positive proportion also decreased to 3/5 of that
before the outbreak of COVID-19 (10). Studies have shown that the number of pediatric
outpatients and inpatients in many countries decreased substantially in 2020, when the
COVID-19 pandemic began (17–19). A study showed that the number of children
FIG 2 The epidemic trend and demographic characteristics of respiratory viruses in the first year. (A) Monthly activity patterns of viruses. (B) The proportions of
hospitalized for infectious diseases decreased by 37%, among whom the number of
children with respiratory infections decreased by 33% (20). Similar reductions were
observed in this study, with decreases of 31% for inpatients. At the same time, the study
found that the relevant reasons may be related to the adoption of serious intervention
measures, i.e., social distancing and especially school closures, leading to a sharp
reduction in contact between children, which may have reduced the risk of ARTI
transmission. On the other hand, parents’ concerns about sick children and their seeking
of timely clinical care may not play an important role (20). Moreover, the Chinese
government implemented similar public preventive measures after the outbreak of
COVID-19. Our results showed that the number and positive proportion of respiratory
viruses among children of all ages decreased significantly. This finding indicates that NPIs
to control SARS-CoV-2 transmission were also effective in reducing the transmission of
respiratory viruses among children during the COVID-19 pandemic.
During the study period, the number of boys infected with ARTIs and the positive
proportion of virus detection were significantly higher than those of girls, which is
consistent with previous studies, and it is reported that boys may be more susceptible to
ARTIs than girls (10, 21). The study revealed that the genetic susceptibility of children to
respiratory diseases is related to the type of virus and specific respiratory diseases of
patients. There are few studies indicating that the genetic susceptibility of children to
respiratory infectious diseases is related to sex (22–24). Meanwhile, in the gender
composition of children in Chengdu, boys accounted for 50.26%, girls accounted for
49.74%, and the proportion of boys and girls was basically the same. Therefore, we did
not normalize the ratio of virally infected boys vs. girls to an uninfected population.
Children under 3 years of age were the main population with ARTIs (67%). The
possible reason is the waning of maternal antibodies after 6 months and the fact that the
immune system gradually matures after 3 years of age. At this age stage, children lack
FIG 3 The epidemic trend and demographic characteristics of respiratory viruses in the second year. (A) Monthly activity patterns of viruses. (B) The proportions
antibodies against viral infections and are more easily infected by viruses (25). In this
study, the number of inpatients was significantly higher than that of outpatients. The
possible reason is that this testing requires a long time and outpatients hope to obtain
the test results as soon as possible to visit the doctor, resulting in a smaller number of
tests than those for inpatients. At the same time, the main positive proportion of virus
detection among outpatients involved RSV, influenza A and B, and the main positive
proportion of virus detection among inpatients involved RSV, which is consistent with
the relevant research reported (26, 27).
Our previous research revealed that children under 5 years of age were mainly
infected with RSV and influenza A, and children aged 5–10 years were mainly infected
with influenza A (10). During the pandemic, we found that children under 3 years
of age were mainly infected with RSV, children aged 3–6 years were mainly infected
with influenza A, and children aged 6–14 years were mainly infected with influenza
A. Relevant studies have also shown that the population susceptible to RSV is mainly
infants and young children and the detection rate of RSV decreased with age, owing
to the maturation of the immune system (28, 29). According to statistics, RSV causes at
least 3.4 million hospitalizations and between 66,000 and 199,000 deaths among young
children under 5 years of age every year (30). Meanwhile, the influenza virus prevalence
increased with age, which was similar to previous reports (31, 32). Based on the results
of this study, it is possible that there was no significant change in the population
susceptible to viruses after the COVID-19 pandemic. Our previous data showed that
influenza A was the most common virus in this area before the COVID-19 pandemic,
followed by RSV and influenza B (10). In this study, the most common virus detected in
children with ARTIs was RSV, followed by influenza A and B 2 years after the COVID-19
pandemic. This may have been due to NPIs applied during the COVID-19 pandemic,
during which student learning changed from traditional classroom teaching in schools to
online learning at home. School-age children are susceptible to influenza infection, and
decentralized teaching reduces the risk of this infection. Combined with the increased
number of RSV infections, influenza A and B infections may be mainly transmitted
in schools, while RSV may be mainly transmitted within the family or community.
Additionally, influenza virus vaccination may not be a convincing factor. Under the
influence of COVID-19, the willingness to receive influenza vaccines has increased to
avoid double infection with influenza viruses and SARS-CoV-2 (33). Even so, compared
with other countries, China’s influenza vaccination coverage is very low, far from the
herd immunity threshold (34). The vaccination of COVID-19 vaccine in Chinese children
began in October 2021, and the first round of vaccination was completed at the end
of December 2021. We analyzed the rates of positivity for respiratory viruses in January
2022–February 2022. Compared with the positive proportion for respiratory viruses from
January to February 2021, there was no significant change in 2022. The observation time
after the new coronavirus vaccination in children was only 2 months, and a longer time is
needed in future studies.
The positive proportion of viral infections increased significantly between September
2021 and January 2022. Further analysis showed that the positive proportion of influenza
B was significantly higher than that of other viruses, thus increasing the total positive
proportion of the virus. At the same time, the data released by the National Influenza
Center of China showed that the number of cases of influenza B infection increased
substantially during this period (35). Therefore, we speculate that the increased positive
proportion of influenza B may be related to the influenza B epidemic. After excluding
cases of influenza B, the monthly trend of the positive proportion of respiratory virus
detection during the study period was generally consistent. Although the positive
proportions in the autumn and winter seasons were higher than those in the spring
and summer seasons, the degree of change in the positive proportion by seasonality was
ACKNOWLEDGMENTS
This work was supported by the Foundation (No. 21H1219 and No. 22H1407) and the
Science & Technology Department of Sichuan Province (No. 2023YFS0186). The funders
played no role in the study design, data collection and analyses, decision to publish, or
manuscript preparation.
AUTHOR AFFILIATIONS
1
Department of Laboratory Medicine, West China Second University Hospital, Sichuan
University, Chengdu, Sichuan, China
2
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan
University, Ministry of Education, Chengdu, Sichuan, China
FUNDING
DATA AVAILABILITY
The raw data supporting the conclusions of this article will be made available by the
authors, without undue reservation.
ETHICS APPROVAL
The study protocol was approved by the Ethics Committee of West China Second
University Hospital of Sichuan University.
ADDITIONAL FILES
Supplemental Material
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