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.