Changing clinical characteristics of pediatric inpatients with pneumonia during COVID-19 pandamic: a retrospective study

Pneumonia is the leading infectious cause of death amongst children worldwide. It accounts for more than 138 million new cases and almost one million deaths annually, mostly amongst children under 5 years old [1, 2]. Numerous pathogens, both viral and bacterial, are involved in pediatric pneumonia. Research showed a concomitant decrease in all-cause pneumonia during the COVID‐19 pandemic in China [3]. These changes might have come from the competition of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with other respiratory viruses, but they were more likely to have come from improvements in population hygiene practices to prevent SARS-CoV-2 transmission, such as wearing facemasks, paying attention to hand hygiene [4].

SARS-CoV-2 is the third zoonotic and highly pathogenic coronavirus to emerge in the twenty-first century [5]. And the virus has underwent frequent mutations and recombinations, yielding new variants that can cross the species barrier [6]. The World Health Organization (WHO) has identified five variants of concern as Alpha, Beta, Gamma, Delta, and the latest one named Omicron [7]. COVID-19 caused by SARS-CoV-2 emerged in December 2019 in Wuhan, Hubei Province, China [5]. On 11 March 2020, the WHO declared the COVID-19 pandemic. Since then, the number of globally confirmed COVID-19 cases has been increasing exponentially, which has engendered substantial health and economic burdens worldwide [8]. Governmental agencies of different countries worldwide have been widely promoting several measures to prevent the COVID-19 outbreak. Before the vaccination programme at the end of 2020, the fight against the COVID-19 epidemic mainly relied on preventive measures, including encouraging individual-level hygiene (wearing a mask outside, keeping social distance, disinfecting with alcohol and washing hands frequently) and community-level prevention measures (promotion of remote work and study, suspension of mass gathering) [9‐12]. These non-pharmaceutical interventions (NPIs) not only decrease the spreading of the SARS-CoV-2, but also have impact on the prevalence of other pathogens [13‐15]. Moreover, public health measures during COVID-19 have led to an unprecedented change in social lifestyle which might have effect on the allergen sensitization and micronutrient levels in population [16, 17].

In this context, our study aimed to compare the pathogen, allergen and micronutrient characteristics of pediatric inpatients with pneumonia prior to and during the COVID-19 pandemic in a large tertiary hospital in Shanghai, China.

We found that between March-August 2020, the number of children hospitalized with pneumonia at Xinhua Hospital was decreased by 74% compared with the same period of 2019. Recent studies have witnessed a significant reduction in the numbers of pediatric admissions in 2020 in many other countries, including France, the United States and Morocco [20, 21]. This was due to the recommendations imposed at the beginning of the pandemic to avoid access to hospital, except in cases of real need, and also to the public fear of SARS-CoV‐2 infection in the hospital [22]. Additionly, the change in lifestyle during the COVID-19 pandemic might also have reduced the onset of respiratory viral diseases by preventing much person-to-person disease transmission [23, 24]. In other words, this reduction could be considered as an unexpected positive consequence of the NPIs taken during the COVID-19 pandemic, which may have led to a decrease in morbidity and healthcare costs of the infectious diseases [25].

For pathogens, our results showed that viral, Mp and mixed infection rate was reduced respectively in 2020 in children with pneumonia, which was similar to Pengcheng Liu et al’s, Ying Zhang et al’s and Huang QS et al’s reports, possibly because of the use of stringent NPIs such as lockdown and border closures in 2020 [25‐27]. However, in our study, the detection of coxsackie virus increased compared with 2019. The result is in line with the study of Andrew Po-Liang Chen et al’s in Taiwan [28]. Since coxsackie virus is a non-enveloped virus, it might be inherently less susceptible to inactivation by ethanol-containing disinfectant [29]. This viral property might hamper the preventive effectiveness using routine hand disinfectants. Furthermore, Leung et al’s randomized control trial suggests that face mask is more effective in filtering out enveloped viruses than non-enveloped viruses [30]. Consequently, chloride- and hydrogen peroxide-based products should be added for comprehensive infection control. In addition, it is important that coxsackie virus should continue to be monitored diligently in children during the COVID-19 pandemic. And the diseases caused by coxsackie virus should be taken seriously such as hand-foot-mouth disease (HFMD) or herpangina.

Change in lifestyle could trigger the change of people’s susceptibility to various allergens [16]. Our study showed that the positive rates of allergens, including house-dust mite, shrimp and crab in 2020 were significantly higher than those in 2019 in children with pneumonia. The increasing positive rate of house dust mite during the COVID-19 pandemic might be because people stayed at home for a long time with poor ventilation. Shanghai has a humid subtropical monsoon climate. The lack of ventilation led to long-term high relative humidity and lack of sunshine in the house, which were more conducive to the accumulation and reproduction of dust mites in carpets, pillows, and mattresses [31, 32]. Moreover, house dust mite allergen, Der p1, exerts several key activities on the airway mucosa [33]. Such molecules have been shown to favor oxidative stress of the respiratory mucosa and, thus, to exacerbate inflammatory conditions such as asthma or allergic rhinitis [34]. Regarding shrimp and crab allergens, the reason would be that people’s eating habits had been changed during the pandemic and it also might be related to the co-sensitization with the increasing positive rate of house dust mite [35]. Therefore, during home isolation, our room should be fully ventilated, and the sheets and blankets should be washed frequently.

Our study found that hospitalized patients with pneumonia in children presented the lower levels of vitamin B2, B6, C and 25(OH)D in 2020 than those in 2019. The possible reason would be that the COVID-19 lockdown has affected the dietary habits and nutritional patterns. It has been reported that the dietary patterns of Chinese people during the COVID-19 lockdown changed, showing a decrease in the frequency of intake of fresh vegetables and fruit, rice, poultry, meat, and soybean products [36]. However, certain nutrients such as vitamin A, vitaminB2, vitamin B6, vitamin B12, vitamin D, vitamin C, and the minerals Ca and Zn, are important for proper immune function [37]. Deficiencies and a suboptimal nutritional status of these micronutrients could potentially favor the spread of diseases by reducing resistance to infection and reinfection [17]. For example, the vitamin D receptor is expressed in almost all types of cells of the immune system and the correct immune system function will depend on the correct bioavailability of vitamin D from these cells [38]. For vitamin C, it also has roles in several aspects of immunity, including supporting leucocytes migration to sites of infection, phagocytosis and bacterial killing, natural killer cell activity and antibody production [39]. To date, despite the existence of several vaccines in motion to deal with the SARS-CoV-2, the global population must learn to live for a longer time with the virus among us [17]. Therefore, we should keep a healthy and balanced diet in our daily life to strengthen our natural defense system.

There were some limitations in this retrospective study. First, our report was a single-center study, and we only enrolled pneumonia inpatients in our clinical center between March-August 2020 when all students studied online at home and stringent public health measures were adopted during the COVID-19 pandemic. From September 2020, students went back to school. As the control, pneumonia inpatients in the same period of 2019 were recruited prior to the COVID-19 pandemic. Our results were based on a small number of pneumonia cases, and thus they should be interpreted with caution and confirmed in future studies. Second, the identification of the pathogens responsible for pneumonia remains challenging, particularly when mixed infections occur. A proportion of children in this study had no proven causal pathogen. The low detection rate of bacteria and viruses in our study may be due to the fact that some inpatients received antibiotic therapy in outpatient department. The use of next-generation sequencing for pathogen detection could be a useful additional method. Third, only five main allergens were analyzed in this study. Finally, the effects of micronutrient supplementation was not taken into account due to lack of information in this aspect.

The data in this study suggest that number of children hospitalized with pneumonia and incidence of common pathogen infections were both reduced, and that allergy and micronutrient status in children were also changed after the outbreak of the COVID-19 pandemic and adoption of stringent public health measures.