Discussion
During the COVID-19 pandemic, the NPI have profoundly impacted allergen sensitization. This study reached the following conclusions by analyzing the results of inhaled allergen sIgE testing in 29,926 cases before and during the COVID-19 pandemic: (1) During the pandemic, the positive rate of indoor and outdoor allergens increased significantly, and the outcome remained the same after adjusting potential influencing factors such as gender, season, and age. (2) Dust mite allergen sIgE grade and multiple sensitization rate have increased during the COVID-19 pandemic. (3) The allergens sensitization differed by gender, age, and season.
The risk of indoor allergen sensitization during the COVID-19 is 1.2 to 4 times higher than that before the COVID-19 (OR range:1.194~4.014, P<0.05) . Li Y[8] discovered that the positive rate of indoor allergens in South China increased dramatically during COVID-19 pandemic. The study of Qing Ye[9] also observed that the positive rate of allergens during COVID-19 was 51.50%, higher than 42.23% before COVID-19. Additionally, another study of Qing Ye[10] discovered that the positive rate of indoor allergens increased during COVID-19, while the number of positive allergens decreased. But in our study, the number of allergens also increased remarkably during COVID-19. The following factors may be studied to determine the reason for increased positive rate of indoor allergens: (1) NPI during the COVID-19 pandemic increased population density, indoor temperature and humidity[11], as well as the time that pets spent indoors[12], causing the growth of indoor allergen concentrations[9]. Wahn[13]found a dose-response relationship between inhaled allergen exposure and allergen sensitization. Another study[14]indicated that 2ug/g of dust mites in the air was a risk factor for sensitization, whereas 10ug/g was a risk factor for asthma among dust mite-sensitized persons. (2) The increasing concentration of other allergens in the air, such as mold and animal fur, will also increase the risk of dust mite allergens sensitization, because of the cross-reaction[15]. (3) During the COVID-19 pandemic, children spend more time indoors, which increases their chances of being exposed to indoor allergens[16]. Repeated exposure is easy to cause allergens sensitization. It is recommended that individuals use dehumidifiers, vacuuming, air purification, acaricides, and open windows frequently for ventilation to reduce indoor temperature and humidity. Additionally, allergen-reducing measures, including removing carpets and fabric curtains, washing and replacing mattresses and pillows, cleaning air conditioner should be adopted to reduce the accumulation of indoor allergens[17].
Though wearing disposable medical masks for a longer period during the pandemic can prevent the inhalation of allergens theoretically, this study revealed that the positive rate of outdoor allergens actually increased during the pandemic (P <0.05). The result contradicts the study of Qing Ye [10]. There are five factors contributing to the increase in outdoor allergen sensitization rate during the pandemic. Firstly, the masks currently used on children are merely scaled-down copies of masks created for adults which have not been specifically tested or approved[18]. A research on FFP masks proved that wearing a mask could not completely prevent allergen inhalation due to facial leakage penetration and increased total inward leakage caused by higher breathing frequencies[19]. Second, several studies have demonstrated that long-term mask use without change increases the chance of severe skin reactions[20], and the impaired skin barrier provides a pathway for allergen sensitization[21].  Moreover, outdoor activity and allergen exposure increased with the gradual resumption of work and school in the second half of 2020, which is proved by a significant rise in the positive rate of w6 from June to September during COVID-19 in this study, Furthermore, as children usually feel hot and have breathing difficulties while wearing masks, some of them may remove the masks during physical activities[22], raising the prevalence of outdoor allergens during the pandemic. To decrease allergen stimulation and allergy symptoms, it is recommended that children reduce outside activities and use adequate masks with timely replacement during the pollen season.
During the COVID-19 pandemic, the proportion of medium and high-level sIgE to dust mite allergens increased, whereas the proportion of middle and high-level sIgE to mold and cockroach allergens dropped (P<0.05). In the same study, Qing Ye[9]discovered that, except for dust mite allergens, the majority of allergen-specific IgE levels were lower than those before the pandemic. This may also contribute to increased exposure to dust mite allergens by longer time indoors during the pandemic[16].
Moreover, the proportion of multiple sensitivities grew greatly during COVID-19 compared to that before the same period (P<0.05) . Studies have pointed out that  dust mite sensitization is often associated with other allergens due to antigen-cross and co-sensitivity across allergens[23]. Therefore, when advising patients to avoid allergens, doctors should not only focusing on the target allergen while ignoring other frequent allergens. Studies have shown that avoiding a single allergen cannot prevent allergy sensitization, whereas reducing the levels of numerous inhaled allergens together can achieve this purpose[24].
There were gender differences in the positive rate of allergens, which has been reported in other pieces of literature[25], yet the reason and mechanism remain unknown. It could be the different living habits between men and women, which may result in varied allergen exposure[25], or the difference in hormone secretion between the two genders[26].
The positive rate of inhaled allergens changes with age. The positive rates of dust mites and cockroaches increased with age, as found in the studies of Ying[25], and D’Souza[27]. The differences in allergen sensitization at different ages, due to the different range of activity at different ages, might result in differences in allergen exposure. Clinicians should give recommendations to patients properly in avoiding allergen sensitization based on the distribution characteristics of allergens in different age groups and the trend of allergen sensitization with age.
This study also discovered that the positive rate of inhaled allergens was higher in summer and autumn than in winter and spring, and similar conclusions were found in an analysis of allergen sensitization in children in Shanghai, China[25]. This is due to seasonal differences in allergen concentrations in the air caused by the characteristics of various allergens. Dust mite reproduction peaked in July and August and began to decline in October[28]. Animal hair sheds primarily in the summer and autumn. Trees bloom in the spring, grasses in the late spring to early summer, and weeds in the autumn [29]. As a result, patients who are sensitive to inhalation allergens should wear masks based on the seasonal distribution characteristics of local allergens to avoid contact with allergens and reduce allergen stimulation and allergic reactions.
There are currently few studies investigating the impact of the COVID-19 pandemic on allergen distributions. This study offers nearly 30,000 test results from large sample size and includes an analysis of indoor and outdoor allergens, which can be used as a reference for the prevention and control of allergens sensitization under normal pandemic conditions. Nevertheless, this study has some limitations. It lacks data on allergy diseases in the study population for the privacy of the study population, making it impossible to assess the association between the COVID-19 pandemic and allergic diseases. Future studies can therefore investigate whether the COVID-19 pandemic influences the prevalence of allergy diseases.