Impact of COVID‐19 pandemic on influenza virus prevalence in children in Sichuan, China

Abstract

We performed a retrospective analysis of influenza A and B virus antigen detection data in children in Sichuan Province from January 2019 to December 2021, with the goal of studying the impact of the COVID‐19 pandemic on influenza circulation in children in Sichuan, China. During the pandemic, both the number of specimens and the positive rates of the influenza virus fell dramatically. The positivity for influenza A virus decreased from 22.5% in 2019 to 9.9% in 2020 to 0.2% in 2021 (p < 0.001). The lowest and highest positive rates for the influenza B virus occurred in 2020 and 2021, respectively, with a statistically significant 3‐year comparison (p < 0.001). During the pandemic, the annual positivity remained higher in school‐age than in preschoolers, while there was no difference in the annual positivity between the two gender groups, both consistent with the prepandemic results. During the pandemic, the seasonality of influenza A and B was different from that before the pandemic. In 2019, the epidemic season for influenza A was autumn and winter, while the epidemic season for influenza B was winter and spring. Seasonal changes in influenza A were insignificant after the pandemic, and influenza B became predominant in 2021, with a high prevalence in the autumn. Although influenza activity decreased during the COVID‐19 pandemic, one should be on the lookout for a possible rebound in influenza circulation in the future.

1. INTRODUCTION

From 2020 to the present, the 2019 coronavirus disease (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has ravaged the world and has had a major impact on the behavioral habits of the population. Public health interventions such as wearing personal protective equipment like masks, increasing social distance, reducing indoor gatherings, and improving hygiene can reduce not only the spread of COVID‐19 but also the incidence of airborne or fecal‐oral transmitted diseases such as the common cold, seasonal influenza, bronchitis, gastroenteritis, and so forth. ¹

Influenza is an acute respiratory infection caused by influenza viruses (IVs) that poses a constant threat to global public health security through recurring seasonal epidemics and irregularly occurring pandemics. IVs are rapidly evolving viruses of four types, namely influenza A virus (IAV), influenza B virus (IBV), influenza C virus (ICV), and influenza D virus (IDV). Of these four types of IVs, IAV and IBV are the main pathogens causing respiratory disease in humans. Influenza epidemics can lead to not only an increase in outpatient visits and hospital admissions but also a high number of serious illnesses and deaths, resulting in a severe disease load and socioeconomic burden. ² , ³ An estimated global average of 389 000 (uncertainty range 294 000–518 000) respiratory deaths per year are associated with influenza, equivalent to ~2% of all annual respiratory deaths. ⁴

The IV can infect people of all ages. Children are especially vulnerable because their immune systems differ from those of adults. ⁵ Studies show that children <5 years of age are more likely to develop severe, even fatal cases of IV infection. ⁶ It is estimated that at least 28 000–111 500 deaths in children <5 years of age worldwide each year are associated with IV infection. ⁷ Given the susceptibility and severity of IV infection in children, surveillance of influenza infection in children is critical. Continuous surveillance of IVs not only provides insight into their epidemiological characteristics, variability, and the influenza vaccine component and timing but also predicts epidemic trends and provides a scientific basis for the formulation of influenza prevention and control strategies. However, it is unclear how influenza viral and clinical epidemiological characteristics of children presenting with influenza‐like illness (ILI) during the COVID‐19 pandemic in China have changed.

We conducted a retrospective study of IV detection results in children in Sichuan, China, to better understand the influence of the COVID‐19 pandemic on influenza circulation. Sichuan province is located in southwest China and has a total area of 486 000 km² and a resident population of 83.67 million, ranking fifth in China in terms of population, with 13.47 million people aged 0–14 years accounting for 16.1% of the total population. The analysis of IV prevalence in the past 3 years (2019–2021), thus determining the changes in IV positivity, population age, virus type, and the epidemic season before and after the COVID‐19 outbreak, can provide a reference for the prevention and control of influenza in local children and the development of influenza vaccination programs.

2. METHODS

2.1. Study design

The data for this study were obtained from the Sichuan Provincial Maternal and Child Health Care Hospital. It is a tertiary‐level maternal and child healthcare institution that integrates medical, health care, public health, teaching, research, and training functions, and is one of the largest children's specialty hospitals in Sichuan Province in southwest China. The hospital is in Chengdu, the capital of Sichuan province and an important central city in western China, with a population of 21.19 million, accounting for one‐quarter of Sichuan province's population. The children involved in the study were from all 21 prefectures in Sichuan Province and lived locally for more than 6 months, of which 51.5% lived in Chengdu for a long time.

The data collected in this study was from January 2019 to December 2021. The criteria for data inclusion were (1) children, <18 years of age; (2) patients with ILI symptoms, such as fever axillary temperature (>37.5°C), runny nose, nasal congestion, cough, sore throat, headache, myalgia, fatigue, and so forth; and (3) antigen detection data for IAV and IBV were available for each specimen.

Data grouping: (1) grouped by year; (2) grouped by gender; (3) grouped by age, that is, preschool‐age group (≤5 years) and school‐age group (>5 to <18 years).

The study was approved by the ethics committee of Sichuan Provincial Maternal and Child Health Care Hospital. This retrospective study did not involve any personal, private information about the patient and only a statistical analysis of available test data was performed. The committee waived the need for individual informed consent.

2.2. Rapid IVs antigen test

Nasopharyngeal samples were collected from patients. The Clearview Exact Influenza A&B kit (Hangzhou Abon Biomedical Co.) was used for rapid antigen detection (a colloidal gold‐based immunochromatographic assay) according to the manufacturer's instructions. The presence of the control band, along with a test band corresponding to A or B antigen, was considered a positive result. The minimum sensitivity of the kit is 1.25 × 10³ CEID₅₀ (50% Chicken Embryo Infection Dose) per test for IAV and 0.5 × 10³ CEID₅₀ per test for IBV. The reagents are not cross‐reactive to other respiratory pathogens. The test results showed a positive compliance rate of 71% and a negative compliance rate of 99.33% with the test results of the IAV isolated culture method, and a positive compliance rate of 90% and a negative compliance rate of 100% with the test results of the IBV isolated culture method. The results of the kit showed good agreement with those of the reference method.

The number of specimens collected in 2019, 2020, and 2021 was 11 721, 3406, and 3882, respectively, of which the number of positive specimens was 4125, 556, and 1169, respectively.

2.3. Statistical analysis

The statistical analyses were performed using IBM SPSS Statistics for Windows (version 19.0.; IBM Corp.). Comparisons between the groups for the categorical variables were made using Pearson's χ ² or Fisher's exact tests, as appropriate. Group comparisons were also made in pairs with χ ² or Fisher's exact tests according to Bonferroni corrections. All of the tests were two‐tailed, and a value of p < 0.05 represented statistical significance.

3. RESULTS

3.1. Overview of ILI surveillance

The number of visits to children with ILI from 2019 to 2021 was 50 013, 15 103, and 16 988, respectively. The annual ILI% was 13.2%, 6.4%, and 8.7%, respectively, with statistically significant differences (χ ² = 7952.707, p < 0.001) (Table 1). After the COVID‐19 pandemic, the number of ILI and ILI% decreased significantly.

Table 1.

Influenza test rate, ILI%, and influenza positivity in Sichuan Provincial Maternity and Child Health Care Hospital, China, from 2019 to 2021

Year	Total number of visitsa	Total ILI cases (%)b	Total of influenza tests (%)c	Influenza positive (%)d
2019	378 669	50 013 (13.2)	11 721 (23.4)	4125 (35.2)
2020	234 654	15 035 (6.4)	3406 (22.7)	556 (16.3)
2021	195 613	16 988 (8.7)	3882 (22.9)	1169 (30.1)
2019–2021	808 936	82 036 (10.1)	19 009 (23.2)	5850 (30.8)

Abbreviation: ILI, influenza‐like illness.

^a The total number of outpatient and emergency visits.

^b The number of ILI cases and the percentage of total visits.

^c The number of ILI cases tested for influenza virus antigens and their percentage of them.

^d The number of positive flu antigen test specimens and their percentage of the total of tested specimens.

3.2. Clinical characteristics of influenza detection cases

A total of 19 009 nasopharyngeal samples from ILI cases were collected for influenza antigen test over 3 years, and the influenza test rates were 23.4%, 22.7%, and 22.9%, respectively, with no statistically significant differences (χ ² = 5.205, p = 0.074). Of these ILI cases, more than 90% of the children came from cities and towns, and more than 85% were normally in good or very good health. Influenza‐like symptoms mainly include fever (temperature ≥ 38°C) (98.2%), cough (72.0%), rhinorrhea (56.8%), and sore throat (54.3%). 1.3%, 1.5%, and 2.3% were treated with hospitalization in 2019, 2020, and 2021, respectively, with no statistically significant difference in the 3‐year hospitalization rates (χ ² = 5.243, p = 0.073). It was found that 53.4% of children with ILI had close contact with primary cases history of fever or acute respiratory infection. A clear history of exposure was found in 57.9%, 45.0%, and 47.3% of cases in 2019, 2020, and 2021, respectively (χ ² = 250.65, p < 0.001). The primary contacts of these cases were family members, accounting for 49.3%–68.3.0%, with the highest rate in 2020. See data in Supporting Information: Table S1 for more details.

3.3. Comparison of the number of specimens

The number of specimens collected for IV antigen testing in 2019, 2020, and 2021 was 11 721, 3406, and 3882, representing 61.7%, 17.9%, and 20.4% of the total, respectively. Compared to 2019, the number of specimens in 2020 and 2021 decreased by 71% and 66.9% year‐on‐year. It is worth noting that the number of specimens in January 2020 accounts for 61.1% of the total number of specimens in that year, which is higher than the number of specimens in the same month in 2019 (The number of specimens per month is shown in Supporting Information: Figure S1).

The ratio of males to females for each year from 2019 to 2021 was 1:0.9, 1:0.9, and 1:0.8, respectively, with no significant change in the ratio of males to females. 11 845 (62.3%) of the 19 009 specimens were from preschool‐age children, while 7164 (37.7%) were from school‐age children. Over the 3 years, the ratio of specimens from the two age groups was 1:0.6, 1:0.3, and 1:1, respectively. The number of specimens from the two age groups varied significantly over the 3 years, most notably in 2020, when the number of specimens from school‐age children was only 30% of that of preschool‐age children. (See data in Supporting Information: Table S1 for more details.)

3.4. Comparison of IVs positive rates by year

In 2019, 2020, and 2021, the number of positive specimens for influenza antigen testing was 4125, 556, and 1169, respectively, with positive rates of 35.2%, 16.3%, and 30.1%, respectively, with statistically significant differences (χ ² = 442.064, p < 0.001). The positive rate for influenza in 2019 was higher than those in the following 2 years. As shown in Figure 1, in both 2019 and 2020, the positive rate of IAV was higher than that of IBV and co‐infections (2019: χ ² = 2840.745, p < 0.001; 2020: χ ² = 328.771, p < 0.001). And in 2021, the positive rate of IBV was significantly higher than that of IAV and co‐infections (χ ² = 2539.203, p < 0.001). A 3‐year comparison of positive rates for influenza A infection found that the positive rate of IAV was significantly higher in 2019 than in 2020 and 2021 (χ ² = 1204.166, p < 0.001). A comparison of positive rates of IBV over the 3 years revealed that the highest positive rate was found in 2021, followed by 2019, and the lowest in 2020, with a statistically significant difference (χ ² = 925.365, p < 0.001). The 3‐year difference in IAV and IBV co‐infection positive rates was not statistically significant (χ ² = 1.226, p = 0.542). (See data in Supporting Information: Table S1 for more details.)

Figure 1.

Comparison of positive rates for influenza viruses from 2019 to 2021. (A) Trends in influenza virus positivity from 2019 to 2021; (B) Comparison of positive rates for IAV, IBV, and co‐infection. ***The P‐value is less than 0.001. IAV, influenza A virus; IBV, influenza B virus.

3.5. Comparison of IVs positive rates in children of different age groups

We compared the positive rates of the IV between the two age groups and discovered that the school‐age group had higher positive rates than the preschool‐age group each year from 2019 to 2021 (2019: χ ² = 429.725, p < 0.001; 2020: χ ² = 44.181, p < 0.001; 2021: χ ² = 347.232, p < 0.001). The positive rates were similar for both virus types, that is, annual positive rates for either IAV or IBV were higher in the school‐age group than in the preschool‐age group (except for the IAV positive rate in 2021). In addition, we analyzed the annual positive rates of both IV types in different age groups. As shown in Figure 2, in the preschool‐age group, the IAV positive rates were 20.8%, 9.3%, and 0.2% in 2019, 2020, and 2021, respectively, with statistically significant variations (χ ² = 598.792, p < 0.001). For 3 years in a row, the IBV positive rates were 7.1%, 4.7%, and 16.1%, respectively, and the differences were statistically significant (χ ² = 220.986, p < 0.001). The same pattern was observed in the school‐age group for all 3 years. (See data in Supporting Information: Table S2 for more details.)

Figure 2.

Three‐year comparison of IAV and IBV positivity rates in preschool and school‐age children. ***The P‐value is less than 0.001. IAV, influenza A virus; IBV, influenza B virus.

3.6. Comparison of IVs positive rates in children of different gender groups

A comparison of IV positive rates for boys and girls from 2019 to 2021 revealed no statistically significant difference in annual positive rates between gender groups for each year. Furthermore, there was no statistically significant difference between the two groups in annual positive rates for IAV and IBV per year. The maximum positive rates for IAV and IBV in both groups appeared in 2019 and 2021, respectively. (See data in Supporting Information: Table S3 for more details.)

3.7. Changes in the epidemic season of IVs

By comparing the positivity of IVs in the same season in different years, we found that the prevalence of influenza changed during the COVID‐19 pandemic. As shown in the yellow histogram in Figure 3, in 2019, the IAV positive rate exceeded 25% throughout the autumn and winter seasons, that is, January to February and September to December. During the COVID‐19 pandemic, IAV positive rates were low (0.0%–4.2%) in all months except January 2020. The seasonality of influenza B was however different from that of influenza A. As shown in the blue histogram in Figure 3, IBV positivity was high in the winter and spring of 2019, that is, January–April, reaching the highest value of the year (39.3%) in March in particular. In 2020, the monthly positive rates were very low (0.0%–2.7%), except for January. The seasonality of influenza B in 2021 was very different from the previous 2 years, with the highest monthly positive rate occurring in the autumn, from September to November, with October having the highest rate of positivity for the year (43.1%).

Figure 3.

The monthly positive rates for influenza viruses from 2019 to 2021. The gray background shows the time period when Sichuan Province implemented strict epidemic prevention at the beginning of the COVID‐19 outbreak, which also is the winter holidays, Chinese New Year, and the closure of local schools; the timeline diagram above shows specifically the different times when restrictions and types were implemented in Sichuan Province.

A review of the interventions for COVID‐19 implemented in Sichuan since the beginning of 2020 and their timeline (Figure 3) reveals that the time period when monthly influenza positivity was significantly different from the traditional epidemic season coincided with the timing of the COVID‐19 epidemic and the activation of the public health emergency response in Sichuan.

4. DISCUSSION

We conducted this retrospective analysis to understand the epidemiological characteristics of local childhood influenza during the COVID‐19 pandemic. Although not all ILI cases were tested for influenza, the 3‐year influenza detection rate was comparable, which makes the findings of this study convincing.

The findings suggested that a series of multifaceted public health interventions during the COVID‐19 pandemic not only reduced the spread of SARS‐CoV‐2 but also had a significant impact on IV circulation. In the first year of the pandemic, the number of influenza specimens dropped sharply after peaking in January, with the most pronounced drop in the number of specimens from school‐age children. After January, both ILI% and IV positive rates declined significantly, with almost no confirmed cases of influenza for 13 consecutive months from March 2020 to March 2021. The timing of the decline in specimen numbers and influenza activity coincided with the onset of the COVID‐19 epidemic and the start of public health interventions. Beginning in late January 2020, mainland China launched the most comprehensive, rigorous, and thorough prevention and control of the outbreak nationwide. On January 24, Sichuan Province activated Level 1 public health emergency response. On January 25, the NHC released six sets of guidelines on disease prevention: for general use, tourism, households, public places, public transport, and home observation to intervene in the spread of respiratory infectious diseases in many ways. The Chinese government extend the Chinese New Year holiday of 2020 and postpone the opening of all schools and kindergartens. The implementation of these interventions, combined with increased public awareness of respiratory disease prevention (e.g., maintaining social distance, washing hands frequently, wearing masks when going out, etc.), has strongly reduced the incidence of respiratory infectious diseases. Data on the exposure history of children with ILI support this. The proportion of children with close contact with primary cases of fever or acute respiratory infection in these 3 years was lowest in 2020, followed by 2021.

After the COVID‐19 pandemic, the type of local IV epidemic changed. In both 2020 and 2019, IAV was the most prevalent type, but its positive rate decreased year by year. In 2021, IBV positivity surpassed that of IAV and even exceeded IBV levels before the pandemic. The analysis results of influenza data from children in two age groups and two gender groups were also completely consistent with the above results. These findings suggest that locally, regardless of the age and gender of the children, the predominant type of IV they contract has shifted from IAV to IBV. From the 2020 to 2021 influenza season, IBV became the dominant type, which was consistent with the overall surveillance results in China. ⁸ We will continue to monitor how the types of IVs will change in the future.

Many previous studies have found that school‐age children have a higher incidence of seasonal and pandemic influenza than preschoolers. ⁹ The results of our study show the same. Furthermore, the COVID‐19 pandemic had no effect on the difference in IV positive rates between the two age groups of children. Before and during the pandemic, influenza positive rates in school‐age children were higher than in preschool‐age children. The reason for this could be that the COVID‐19 pandemic affected all children's social activities, but school‐age children are at higher risk of influenza infection due to their wider range of activities and exposure to a greater number of people than younger children. In addition, school restrictions or closures introduced in response to the COVID‐19 epidemic may also have had an impact on the difference in influenza prevalence between the two age groups. At the beginning of the pandemic, which coincided with the winter and spring holidays, the local government made the decision to postpone the 2020 spring semester on January 27. Face‐to‐face instruction was canceled in all schools and kindergartens from the end of January to March and did not resume until April. The earliest school opening was for secondary schools, followed by elementary school, and kindergartens did not return to normal until after June. Several localized COVID‐19 outbreaks occurred in Sichuan during the subsequent routine prevention and control of the COVID‐19 epidemic, and parents generally chose to keep their younger children out of school for health reasons.

Some studies suggested that the higher activity of boys may lead to a greater chance of influenza infection in boys. ¹⁰ However, this was not found in our observations. There was no difference in influenza positivity between boys and girls in this region before and during the COVID‐19 pandemic.

We examined monthly IV positive rates over 3 years and demonstrated that the seasonality of influenza during the COVID‐19 pandemic was somewhat different from the prepandemic period. Before the pandemic, the flu season was in the winter, which was consistent with that of most northern hemisphere countries. ¹¹ After the WHO declared COVID‐19 as a pandemic, the seasonal variation of influenza started to become less pronounced. During this period, the highest positivity for IAV occurs in June 2021, but this is only equivalent to June 2019. The positive rate for IBV peaks in the autumn of 2021, which is different from the situation before the pandemic. However, it may be too early to draw conclusions about the change in influenza season after the COVID‐19 pandemic. From February 2020 to September 2021, the results may be biased due to the low volume of specimens and generally low influenza positivity rates, so scientific judgments need to be made in conjunction with data from the new influenza season. Aside from the impact of the COVID‐19 pandemic, the causes of seasonal variation in influenza cannot be ruled out as being linked to changes in the local climate. ¹² As a result, more research on the seasonality of influenza in Sichuan is required.

This study may have some limitations. First, the method used in the study detected seven H1N1 subtypes, five H3N2 subtypes, two H5N1 subtypes, one H9N2 subtype, and one H7N3 subtype of IAV, but not all IAV, thus potentially resulting in false‐negative results; Second, the test is slightly less sensitive to certain IAV subtypes (e.g., HongKong/8/68 subtype, Mal/320/54 subtype, etc.), which could lead to biased results if these subtypes were predominant in 2020–2021; Third, due to the small number of specimens tested each month between February 2020 and September 2021, missed diagnoses may occur.

In conclusion, influenza infections in children during the COVID‐19 pandemic are different from those before the COVID‐19 pandemic in Sichuan, China. A strong “intervention” in Sichuan in response to the COVID‐19 pandemic resulted in a decrease in influenza circulation levels in 2020 and 2021. Although long‐term education on novel coronavirus prevention has greatly increased the population's awareness of self‐protection against respiratory virus transmission, the possibility of a rapid rebound of influenza after the “intervention” subsides still needs to be guarded. IVs and COVID‐19 have similar modes of transmission and clinical features, and therefore share a high degree of consistency in terms of susceptible populations and medical resources required. A high rebound of influenza can not only cause significant health losses but also crowd out healthcare resources. Therefore, during the COVID‐19 epidemic, we should also pay high attention to the circulation characteristics of influenza.

AUTHOR CONTRIBUTIONS

Pinjia Wang, Chengbin Xie, Yidan Xu, and Zhe Su designed the study. Chengbin Xie and Zhe Su collected the data. Pinjia Wang, Yidan Xu, and Chengbin Xie performed the data curation, analysis, and visualization. All authors reviewed and edited the manuscript. All authors had full access to all data in the studies and had final responsibility for the decision to submit for publication.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Supporting information

Supplementary information.

Wang P, Xu Y, Su Z, Xie C. Impact of COVID‐19 pandemic on influenza virus prevalence in children in Sichuan, China. J Med Virol. 2022;95:e28204. 10.1002/jmv.28204

DATA AVAILABILITY STATEMENT

The data that supports the findings of this study are available in the supplementary materials of this article.