Coronavirus Pandemic COVID-19 public health measures reduce the incidence of respiratory infectious diseases

Background: Children and the elderly are two special subpopulations for coronavirus disease 2019 (COVID-19) and respiratory tract infections (RTIs). The study aimed to evaluate the effect of COVID-19 public health measures on the burden of RTIs in China by performing a two-center investigation. Methods: The electronic medical records of all inpatients in departments of pediatrics and respiratory medicine of Taizhou Fourth People’s Hospital (Taizhou, China) and Shaanxi Provincial People’s Hospital (Xi’an, China) during January 1, 2019 to June 30, 2021 were analyzed. A total of 18,084 child inpatients and 14,802 adult inpatients were included. Results: The vast majority (88.3%-90.6%) of the adult inpatients were the elderly, aged over 50 years. The numbers of child and adult (elderly) inpatients, and the proportions of RTI-associated diseases substantially decreased during COVID-19 pandemic (2020-2021) compared to that before the pandemic (2019) in Taizhou and Xi’an. A significantly higher proportion of LRTI-associated diseases was observed in elderly female inpatients (53.4-55.6%) than elderly male inpatients (34.3-41.5%) ( p < 0.001) in spite of more male inpatients than female inpatients (1.94-1.95:1). Conclusions: COVID-19-related interventions provide an additional beneficial effect on reduction of RTI-associated diseases in both children and the elderly. COVID-19; respiratory tract infections (RTIs); children; the elderly; intervention measures; gender.


Introduction
Since late 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 267.3 million infections and 5.28 million deaths globally. The emergency use of several COVID-19 vaccines did not completely stop the transmission of newly generated SARS-CoV-2 variants that have caused several waves of COVID-19 in different countries. Currently, the "Omicron Variant" that can cause vaccinebreakthrough infections has rapidly spread across the world and triggered a new wave of the pandemic [1,2].
Respiratory tract infections (RTIs) are a leading cause of morbidity and mortality globally [3][4][5]. Children and the elderly are two special subpopulations for COVID- 19 and RTIs [4][5][6][7]. Children are less susceptible to COVID-19 with the lowest morbidity and mortality [6], but are highly vulnerable to RTIs (e.g. respiratory syncytial virus (RSV) and rhinovirus infections) [8]. Whereas, the elderly are not only a major high-risk group for COVID-19 with the highest mortality, but also vulnerable to RTIs.
Public health measures, including wearing facemask, social distancing, and quarantine, are effective strategies to stop the spread of SARS-CoV-2, and play a vital role in the control of the pandemic [9][10][11]. Aggressive public health measures were implemented nationwide in China since late January 2020 and showed good results in the prevention and control of the COVID-19 pandemic. Public health measures were previously reported to reduce the incidence of respiratory viral infection in Australia, Brazil, France, Finland, Israel, Japan, Korea, USA, and Singapore [12][13][14][15][16][17][18][19][20][21], suggesting that COVID-19 public health measures have a beneficial role in the containment of non-SARS-CoV-2 respiratory pathogens. Here, we aimed to evaluate the effect of COVID-19 public health measures on frequency and burden of RTI-associated illnesses in children and adults in Taizhou and Xi'an cities of China.

Methods
Public health measures have less effect on hospital admission. To investigate the effect of public health measures on RTIs in children and adults, we analyzed the electronic medical records of all inpatients in departments of pediatrics and respiratory medicine of Taizhou Fourth People's Hospital (Taizhou) and Shaanxi Provincial People's Hospital (Xi'an) between January 1, 2019 and June 30, 2021. The study was approved by Nantong Third Hospital Ethics Committee (E2020003). Overall, data for 3,220 child inpatients and 4,235 adult inpatients in Taizhou, and 14,864 child inpatients and 10,567 adult inpatients in Xi'an was included in the study. The ratios of boys to girls were 1.31:1 and 1.23:1, and the ratios of male to female adult inpatients were 1.94:1 and 1.95:1 in Taizhou and Xi'an, respectively. The age of children and adult inpatients ranged from two months to 16 years old (median 5) and 15 to 99 years (median 73), respectively, in Taizhou city. Meanwhile the age of children and adult inpatients in Xi'an ranged from one month to 16 years old (median 3) and 13 to 100 years old (median 68), respectively. About 66.4% and 80.7% of child inpatients were younger than 6 years old in Taizhou and Xi'an, respectively (Supplementary Figure 1). The vast majority of the adult inpatients were elderly, aged over 50 years, in both cities (90.6% in Taizhou and 88.3% in Xi'an) (Supplementary Figure 1). No significant difference was observed in the age distribution of child and adult inpatients between Taizhou and Xi'an. Comparison of percentages was performed using chisquare test with a p value of 0.05.
To evaluate the effect of COVID-19 public health measures on the burden of RTIs in the two cities, we analyzed RTI-associated diseases. The percentage of RTI-associated diseases significantly decreased in 2020 and 2021 (during COVID-19 pandemic) compared to that in 2019 (before COVID-19 pandemic) in child inpatients in both cities (77.0% and 70.2% vs. 82.8% in Taizhou, 70.0% and 65.5% vs. 83.6% in Xi'an, respectively; p < 0.001 for all) ( Figure 1C). This decrease was mainly contributed by the significant decrease in the incidence of lower RTI (LRTI)associated diseases (p < 0.01 or 0.001), but not by upper RTI (URTI)-associated diseases ( Figure 1C). Similar  Table 1. Statistical analysis was performed by chi-square test. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ns, not significant. decrease in percentage of LRTI-associated diseases during COVID-19 pandemic was also observed in adult inpatients, and this decrease was statistically significant in Xi'an (p < 0.001), but not significant in Taizhou ( Figure 1D). Decreased numbers of child inpatients in pediatrics department and adult inpatients in department of respiratory medicine, as well as significantly decreased percentages of RTI-associated diseases clearly indicate that COVID-19-related intervention measures substantially reduced the incidence of respiratory infectious diseases.
In addition, higher proportion of RTI-associated diseases was observed in boy inpatients (80.0% and 80.2%) as compared to girl inpatients (77.2% and 76.3%) in Taizhou (p = 0.057) and Xi'an (p < 0.001), respectively ( Figure 2). However, significantly higher proportion of LRTI-associated diseases was observed in female adult inpatients (53.4-55.6%) than male adult inpatients (34.3-41.5%) in both cities (p < 0.001). The reason for the gender difference in proportion of RTIassociated diseases between children and old adults is unclear.

Discussion
The elderly and children are vulnerable groups for RTIs, which are the major threat to their health and the foremost cause of deaths [3,5]. The elderly who have accumulated more RTIs and had longer-term exposure to polluted air and/or smoking, often had one or more comorbidities, which result in the worst COVID-19 clinical outcomes [6,7]. Like children, the elderly also have relatively weak immune system, and are vulnerable to RTIs [22]. Community/home transmissions might be the major route for RTIs among the elderly and children due to their relatively less outdoor activities. Simple public health measures such as facemask wearing are predicted to be effective in reducing community/home transmissions of RTIs among high-risk groups. Widespread implementation of public health measures during the COVID-19 pandemic provided an opportunity to see the potential effect of these measures on the incidence of RTIs among vulnerable groups.
Since late January 2020, wearing facemask and other interventions were practiced widely in almost all cities of China and showed excellent effect on the containment of COVID-19 [10,11]. Significant declines in the numbers of child inpatients in department of pediatrics and elderly inpatients in department of respiratory medicine, as well as the percentages of RTIassociated diseases were observed for at least one and a half years in two different cities of China, suggesting that the implementation of these measures also significantly reduced the burden of RTI-associated illnesses, even though the restrictions were somewhat relaxed in 2021. The beneficial impacts of COVID-19 public health interventions were also observed in some other countries, regardless of urban or rural location [12][13][14][15][16][17][18][19][20][21]. This implies that even though these measures are no longer required for containing COVID-19, they can be practiced to some extent to reduce the burden of other respiratory infections.
Gender-specific difference in the incidence rate of RTIs was previously reported in both children and the elderly, and boys/males appeared to have higher RTIs incidence rate than girls/females [5]. Consistently, we observed about twice as many male as female elderly inpatients in both cities, substantially higher than overall men-to-women ratio of 1.00-1.04:1 (National census of China 2021). However, significantly higher percentages of LRTI-associated diseases were observed in elderly women than elderly men regardless of before and during the pandemics. This phenomenon could not to be explained by the differences in the risk of community exposure to RTIs between elderly women and men, but might be involved in the physiological and immunological differences.
In summary, despite some inconvenience and discomfort, COVID-19-related interventions provide an additional benefit of reducing RTI-associated diseases in both the elderly and children.

Acknowledgements
This work was supported by the grant from the Health Commission of Jiangsu Province, China (Z2019038) to ZW. Ratios of boys to girls was 1.31:1 and 1.23:1 in Taizhou and Xi'an, respectively. The ratio of male to female adult inpatients were 1.94:1 and 1.95:1, respectively. The data used in figure 2 is shown in Supplementary Table 2. Statistical analysis was performed by chi-square test. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ns, not significant. M, male; F: female.