Discussion
This study demonstrates that the incidence of SAA at the PICU of the Amsterdam UMC was lower in the first year of the COVID-19 pandemic, which may be a result of lockdown measures protecting children from several asthma exacerbation triggers. Additionally, we observed a high-peak incidence in the fall of 2021 after all governmental restrictions had been lifted, which could be due to an increase in infection rate by viruses other than SARS-CoV-2.
A similar study conducted in Italy showed a decrease in incidence of children with asthma exacerbations visiting the ED during the first and second wave of the COVID-19 pandemic in 2020. They found that this was due to the closing of day care and schools, less air pollution because of reduced travel and fear of visiting hospitals during the peak of the pandemic that in turn led to avoidance or delay in seeking medical care. They also attributed this observation to reduced exposure to viruses; however, they did not evaluate viral triggers in their study13. We found that during the peak period in 2021, respiratory viruses were the most frequent trigger for SAA. It is well known that viral respiratory tract infections are a major trigger for SAA, which typically induces a chemokine-mediated neutrophil pattern4. Due to the COVID-19-related restrictions, including increased hygienic measures, wearing face masks and social distancing, the spread of infectious agents was reduced and thereby asthma attacks diminished11,14. We hypothesize that when restrictions were lifted, children were exposed to these viruses again, explaining the high rate in the peak of 2021. Another reason this peak could be attributed to the “Hygiene Theory”, introduced by Strachan in 1989. This theory states that the trend of allergic diseases may be associated with infectious diseases and unhygienic contact in early childhood could prevent allergic disorders23.
Furthermore, increased hygienic measures during the pandemic may have decreased children’s immune training, which made them more susceptible to infection24. Immunity debt implies the lack of protective immunity caused by prolonged low exposure to a specific pathogen. This makes children susceptible to viral disease, which is particularly of concern for viruses whose transient immunity is acquired through virus contact. For example, respiratory syncytial virus (RSV) maternal antibodies diminish soon after birth and without seasonal exposure immunity declines and susceptibility to subsequent (and possibly more severe) infection increases25. There is also evidence that inducting trained immunity leads to enhanced potency of the immune system against viral infection26. Therefore, we hypothesize that staying at home during the lockdown periods of the pandemic may reduce exposure to a wider range of infectious agents, resulting in a more vulnerable immune system against viral infection as well as an increased risk on asthma exacerbations, which may have contributed to the increase in SAA admissions observed in late 2021. However, as this observation is based on a single hospital, an evaluation of the immunological aspect of asthma exacerbations during the COVID pandemic is required.
Additionally, the COVID-19 pandemic also led to an increased rate of viral testing at the PICU, as the updated infection control measures required an active SARS-CoV-2 infection to be confirmed or ruled out by a rapid test before admission. Nevertheless, more extensive viral testing for respiratory viruses was limited because of decreased laboratory capacity during the pandemic. Thus, even though there was an increased frequency of viral tests taken during the pandemic years, it was usually still unknown what viral agent had caused the respiratory symptoms as our cases were not tested for all agents. Among the detected viral agents, Rhinovirus was the most commonly detected which was also observed in a similar study in Hong Kong from 2015 to 202027.
In a study conducted by Ulrich et al. in the U.S.A., a drastic decline in the number of ED visits due to asthma exacerbations was reported in 2020. This decline was proportionately larger than the decrease in the total number of ED visits. The authors attributed better air quality due to reduced travel as the reason for this decrease in asthma exacerbation rate15. In another study by Papadopoulos et al., it was found that the rate of asthma exacerbations in children was decreased during the pandemic in comparison with 2019. They proposed that this might be the effect of decreased exposure to asthma triggers and increased treatment adherence28. Chauhan et al. found a decrease of ambient PM2.5 concentrations of up to 159% in certain areas during lockdowns, depending on factors such as local meteorological conditions and intensity of lockdown rules29. While there is evidence supporting the association between pollen, PM2.5 concentration and asthma exacerbations18,30, in this study no clear association was found. However, as this observation was based on a single monitoring site, a wider sampling would be required before drawing definite conclusions. This discrepancy might be explained by the more prominent role of a viral infection as a trigger for SAA rather than other triggers such as air pollution and pollen.