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\begin{document}

\title{The effect of the COVID-19 lockdown on children with asthma-related
symptoms: A tertiary care center experience}



\author[1]{Inbal Golan-Tripto}%
\author[2]{Noga* Arwas}%
\author[2]{Michal  Maimon}%
\author[2]{Romi Bari}%
\author[2]{Micha Aviram}%
\author[2]{Dvir Gatt}%
\author[2]{Aviv Goldbart}%
\affil[1]{Soroka University Medical Center}%
\affil[2]{Soroka Medical Center}%


\vspace{-1em}



  
  \date{June 14, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: Acute asthma exacerbations are a common cause for emergency
department (ED) visits and hospitalizations in children. Since the
outbreak of COVID-19 and the education system closure/ total lockdown in
Israel on March 2020, we have noticed a decrease in pediatric ED visits
and an increase in hospitalizations of asthma exacerbations. Objective:
to examine the patterns of ED visits for asthma exacerbations during
COVID-19 outbreak, in comparison to the previous year. Methods: a
retrospective study comparing asthma related ED visits and
hospitalizations among children aged 2-18 years at a tertiary center in
southern Israel. Three time periods were selected: 2020A (pre- lockdown,
1/2/20-14/3/20), 2020B (lockdown, 15/3/20-15/5/20) and 2020 C (post-
lockdown, 16/5/20-30/6/20) and compared to the three parallel time
periods in 2019. Data regarding demographics, number of ED visits and
clinical severity parameters were collected and analyzed. Results: 512
children visited the ED for asthma exacerbation: 273 children during
2019 and 239 children during 2020, with significantly fewer ED visits
per day during the lockdown period (1.8 vs 1.43, p\textless{}0.001),
compared to the parallel period in 2019. Significantly higher
hospitalization rate (47.1\% vs 33.7\%, p=0.05) and longer length of
stay (LOS) (3.15 vs 1.9 days, p= 0.03) were observed during the
lockdown. Conclusion: lockdown is associated with fewer ED visits for
asthma exacerbation, probably due to; reduced exposure to viral
infections and environmental allergens, decreased availability of
primary physicians and families' reluctance to arrive to the ED. ED
visits during lockdown were characterized by higher hospitalization rate
and longer LOS.%
\end{abstract}%



\sloppy


\textbf{The effect of the COVID-19 lockdown on children with}

\textbf{asthma-related symptoms: A tertiary care center experience}

Golan-Tripto Inbal*, MD
\textsuperscript{1,2,5}\emph{inbalgt@clalit.org.il}

Arwas Noga*, MD \textsuperscript{1,5}, noga.arwas@gmail.com

Maimon Michal S, MD\textsuperscript{3,5}, MichalMaimon@clalit.org.il

Aviram Micha, MD\textsuperscript{2,5}, aviram.micha@gmail.com

Gatt Dvir, MD\textsuperscript{1,2,5}, dvirgatt@gmail.com

Bari Romi \textsuperscript{4} BSc, romiba6@gmail.com

Goldbart Aviv, MD \textsuperscript{1,2,5},\emph{avivgold@bgu.ac.il}

*equally contributed

\textsuperscript{1}Department of Pediatrics, Soroka University Medical
Center, Beer-Sheva, Israel

\textsuperscript{2}Pediatric Pulmonary Unit, Soroka University Medical
Center, Beer-Sheva, Israel

\textsuperscript{3}Department of Pediatric Emergency Medicine,
Beer-Sheva, Israel

\textsuperscript{4}Clinical Research Center, Soroka University Medical
Center, Beer-Sheva, Israel

\textsuperscript{5}Faculty of Health Sciences, Ben-Gurion University of
the Negev, Beer-Sheva, Israel

\textbf{Corresponding author:} Dr. Inbal Golan Tripto, Pediatric
Pulmonary Unit\textbf{,} Soroka University Medical
Center\textbf{,}Faculty of Health Sciences, Ben Gurion
University\textbf{,} PO box 151, Beer Sheva, Israel. Tel: +972 8
6403064; Fax: +972 8 6287163. E-mail: Inbalgt@Clalit.org.il

\textbf{Key words:} COVID-19, lockdown, asthma, children, emergency
department

The authors declare that they have no financial competing interests.

This study was not supported by funding sources.

No reprints request.

\textbf{Abstract}

\emph{Background:} Acute asthma exacerbations are a common cause for
emergency department (ED) visits and hospitalizations in children. Since
the outbreak of COVID-19 and the education system closure/ total
lockdown in Israel on March 2020, we have noticed a decrease in
pediatric ED visits and an increase in hospitalizations of asthma
exacerbations.

\emph{Objective:} to examine the patterns of ED visits for asthma
exacerbations during COVID-19 outbreak, in comparison to the previous
year.

\emph{Methods:} a retrospective study comparing asthma related ED visits
and hospitalizations among children aged 2-18 years at a tertiary center
in southern Israel. Three time periods were selected: 2020A (pre-
lockdown, 2/1/20-3/14//20), 2020B (lockdown, 3/15/20-5/15/20) and 2020 C
(post- lockdown, 5/16/20-6/30/20) and compared to the three parallel
time periods in 2019. Data regarding demographics, number of ED visits
and clinical severity parameters were collected and analyzed.

\emph{Results:} 512 children visited the ED for asthma exacerbation: 273
children during 2019 and 239 children during 2020, with significantly
fewer ED visits per day during the lockdown period (1.8 vs 1.43,
p\textless{}0.001), compared to the parallel period in 2019.
Significantly higher hospitalization rate (47.1\% vs 33.7\%, p=0.05) and
longer length of stay (LOS) (3.15 vs 1.9 days, p= 0.03) were observed
during the lockdown.

\emph{Conclusion:} lockdown is associated with fewer ED visits for
asthma exacerbation, probably due to; reduced exposure to viral
infections and environmental allergens, decreased availability of
primary physicians and families' reluctance to arrive to the ED. ED
visits during lockdown were characterized by higher hospitalization rate
and longer LOS.

\textbf{List of Abbreviations:}

COVID-19 corona virus disease 2019

ED Emergency department

LOS Length of stay

PICU Pediatric intensive care unit

\textbf{Introduction}

The coronavirus disease 2019 (COVID-19) outbreak has led, since the
beginning of 2020, to the implementation of ``social distancing''
practices including school closures in many countries, in order to
reduce the transmission of the disease\textsuperscript{1}. When we
analyze the ''lockdown approach'' during influenza pandemic, a mean
reduction of 29.6\% in the peak of the epidemic after school closure was
reported by a systematic review of 31 studies\textsuperscript{2}.
Another review presented a substantial reduction of up to 50\% in the
transmission of disease among children after school closure during
influenza outbreak\textsuperscript{3,4}.

To date, children appear to represent a low proportion out of total
confirmed COVID-19 cases and are usually asymptomatic or present with
mild symptoms\textsuperscript{5}.

Asthma is the most common pediatric chronic respiratory disease. Acute
exacerbations continue to be a major health concern among children
worldwide and a common reason for emergency department (ED) visits and
hospitalizations in the pediatric age. In a study examining
asthma-related ED visits and hospital admissions in the United State
between 2010 and 2015, acute asthma exacerbations accounted for 3\% of
ED visits and 6\% of hospital admissions among children aged 5-17
years\textsuperscript{6}. Respiratory tract infections and allergen
exposure have been recognized as the most common triggers for asthma
exacerbations in children, with suggested synergistic interactions
between these factors\textsuperscript{7}. The seasonal pattern of asthma
exacerbations is well established\textsuperscript{8}. A typical peak is
in September, when children return to school after the summer break. In
school-aged children, another peak has been viewed during the spring
months, that can be attributed to the spread of pollen allergens, also
known as a trigger for asthma exacerbation in this age
group\textsuperscript{9}. There is scarcely any data on whether
childhood asthma constitutes a risk factor for COVID-19
severity.\textsuperscript{10}

Since the introduction of the COVID-19 outbreak and education system
closure in Israel on March 15, 2020, we have noticed a decrease in
pediatric ED visits, specifically for asthma related visits, comparing
to previous years. Similar observations were recently reported with a
decline of 76\% in the asthma related ED visits, and a lower
hospitalization rate, during COVID-19 lockdown.\textsuperscript{11}

Therefore, we aim to examine the patterns of pediatric ED visits for
asthma exacerbations during the COVID-19 outbreak, pre- lockdown, during
lockdown and post lockdown, in comparison to the previous year.

\textbf{Methods}

This is a descriptive, cross-sectional study, comparing the asthma
related ED visits and hospital admissions in Soroka University Medical
Center, a single tertiary center in southern Israel, among children aged
2-18 years. Three time periods were selected: 2020A (pre- lockdown,
2/1/20-3/14/20), 2020B (lockdown, 3/15/20-5/15/20) and 2020 C (post-
lockdown, 5/16/20-6/30/20) and were compared to three parallel time
periods in 2019.

\emph{Patients}

Pediatric patients aged 2-18 years that presented to the ED during one
of the selected time periods for asthma related symptoms (e.g. shortness
of breath, wheezing, tachypnea), and were treated during the visit with
anti-asthmatic medications, were included in the study. Using electronic
health record data, we collected the parameters for each patient,
including relevant medical history and medications. Data collected
included: demographic data, chronic diagnoses, medications prescribed,
vital signs on admission, radiological findings, treatment at the ED,
triage acuity during presentation according to Canadian Triage
Assessment Score\textsuperscript{12}, pediatric ward or pediatric
intensive care unit (PICU) admissions and length of hospitalization stay
(LOS). The study received the approval of the institutional ethics
committee (No. 184-20).

Our primary outcome was number of visits to the ED for asthma related
symptoms during 2020A, 2020B and 2020C, in comparison to 2019A, 2019B
and 2019C. Our secondary outcomes were clinical severity parameters
during the visits, indicating by vital signs, radiology findings, rate
of hospitalizations, rate of hospitalizations in PICU, LOS and LOS in
the PICU. We hypothesized significantly fewer visits during lockdown,
with higher severity parameters. We expected increase in ED visits after
the lockdown, similar to the ''September pandemic'', after summer
vacation\textsuperscript{8}.

\emph{Statistical analysis}

Comparisons of demographic, clinical and chest X-ray imaging as well as
outcomes of admissions were performed with appropriate univariate
analyses. Specifically, nominal variables were compared using Pearson's
chi-square test, continuous variables that matched parametric criteria
were compared by using Student's t-test or One-Way ANOVA (analysis of
variance), and ordinal variables and continuous variables that did not
match parametric criteria were compared by using Wilcoxon or
Mann-Whitney U tests. Continuous variables are presented as mean \selectlanguage{ngerman}±
standard deviation (SD). Categorical data are expressed as percentages.
Statistical significance was defined as p-value \selectlanguage{english}[?] 0.05. Analyses were
performed via IBM SPSS software version 22.

\textbf{Results}

A total of 512 children presented to the ED for asthma related symptoms
during the study periods: 273 children during 2019 (124 in 2019A, 89 in
2019B and 60 in 2019C) and 239 children during 2020 (125 in 2020A, 51 in
2020B and 63 in 2020C). Demographic data were similar except for their
age, which was younger during 2019; median age of 5.2, 5.3 and 4.7 years
during 2019A, 2019B and 2019C compared with 6.7, 6.7 and 6.6 years
during 2020A, 2020B and 2020C, respectively (p=0.06). Male and Bedouin
Arab descent were the majority of the study population in all periods.
There were more visits among Bedouin patients during lockdown, compared
with the parallel period in 2019 (60.7 \% in 2019B vs 78.4 in 2020B,
p=0.002). Similar number of patients with chronic non-respiratory
diseases (e.g. epilepsy, Down syndrome) and chronic respiratory diseases
(bronchopulmonary dysplasia, pulmonary hypertension and obstructive
sleep apnea) or atopy was observed during 6 time periods. Data regarding
the use of chronic respiratory medications; inhaled corticosteroids
(ICS), long acting beta agonist (LABA), short acting beta agonists
(SABA) and leukotriene receptor antagonist (LTRA) is presented
in\textbf{table 1} .

We identified a decrease in use of chronic respiratory treatment in 2020
compared with 2019; 17.7\%, 11.2\% and 20\% during 2019 A, 2019B and
2019C in comparison to 11.2\%, 5.9\% and 6.3\% during 2020A, 2020B and
2020C respectively (p= 0.013). Mean vital signs (fever, blood pressure
and oxygen saturation on room air) were similar between time periods,
except for heart rate (124 vs 115 beats per minute, p=0.039) and
respiratory rate (30 vs 25 breaths per minute, p=0.005) that were lower
during 2020, compared with 2019. Similar rate of abnormal radiological
findings included bilateral hyperinflation, lobar infiltrates and
atelectasis was observed (\textbf{Table 2} ). Treatment during ED visit
included oxygen, inhaled beta agonist and anticholinergic agents,
systemic steroids, inhaled steroids, antihistamines and antibiotics
(\textbf{Table 3} ). Treatments were similar between periods except for
sodium chloride 0.9\% for inhalation, which significantly decreased
during 2020 compared with 2019 (19.6\% vs 48.3 \%, p=0.002).

There was no difference in the triage acuity evaluation on admission to
the ED. We report a significantly fewer ED visits during the lockdown
period, comparing to the parallel period in 2019. A clear trend was
demonstrated during 2019 with fewer visits, as time goes by, in the
spring and summer time. On the contrary, during 2020 we demonstrated
similar visits' numbers prior to lockdown (124 vs 125 visits), with
significant decrement during lockdown (89 vs 51 visits) and increment
post lockdown (60 vs 63 visits). When standardized for number of visits
per day, as the duration of each time period was different (A- 6 weeks,
B- 8 weeks and C- 6 weeks), similar results were observed. Number of ED
visits per day was 3.3, 1.8 and 1.7 during 2019A, 2019B and 2019C
respectively, in comparison to 3.1, 1.4 and 2 during 2020A, 2020B and
2020C respectively (p \textless{}0.001), \textbf{Figure 1a} .

The number of visits per day increased significantly in the era after
lockdown when comparing 2020C to 2020B (2 vs. 1.43 visits per day,
p\textless{}0.001) as well as when compared to the same time period in
2019 (2 vs 1.76 visits per day (p\textless{}0.001) (\textbf{Table 3} ).

During lockdown, hospitalization rate was higher (47.1\% vs 33.7\%,
p=0.05) as was length of stay (3.15 vs 1.9 days, p= 0.03), possibly
indicating higher severity (\textbf{Figure 1b} ). Only 6 patients were
admitted or transferred to the PICU during 6 time periods, 4 of them
necessitated high flow nasal cannula ventilation. There was no
difference in PICU admissions rate or LOS in PICU, between time periods.

\textbf{Discussion}

In this descriptive cross- sectional study, including 512 children who
presented to the ED for asthma related symptoms during 3 time periods in
two consecutive years, we demonstrated different patterns in ED visits
and in hospitalizations during pre-lockdown, lockdown and post lockdown
periods, compared with 2019.

There was no difference in the demographic data between the groups
except for trend towards older age during 2020 compared with 2019. Male
predominance, as can be expected among this pre-pubertal age group, was
observed.\textsuperscript{13} The majority of our patients during all
time periods were of Bedouin Arab descent, with a significant increase
in their visits during lockdown. This could be explained by the low
socioeconomic status of the Bedouin population in southern Israel, some
which are living in large families with overcrowding, poor
accommodations/housing conditions, and limited access to health care in
some of the settlements\textsuperscript{14}. In those areas, social
distancing is more difficult to achieve and the exposure to outdoor
allergens was probably not significantly reduced, even during the
lockdown. The mildly lower heart rate and respiratory rate noticed in
2020 is clinically insignificant and could stem from the difference in
patients age between 2019 and 2020, with an average of 1.5 years older
in 2020. Since asthma severity parameters (hospitalization rate and LOS)
were higher during 2020B, we can assume that this change in vital signs
did not reflect milder cases, but probably proportionate to an older
age. Treatment in the ED was similar between all time periods except for
a significant drop in the use of NACL 0.9\% inhalations during 2020B and
2020C. Since the COVID-19 outbreak, in accordance with the Israeli
pediatric pulmonology society guidelines, there has been a shift from
using small-volume nebulizers to metered-dose inhalers (MDIs) with
valved-holding chambers for beta-agonist and anticholinergic inhalations
in order to reduce the viral infection transmission by reducing the
spread of aerosol mass by small-volume
nebulizers.\textsuperscript{15,16}

The accumulating evidence on the impact of COVID-19 pandemic on ED
visits patterns, show a substantial decrease in the volume of patients
presenting to the ED during the pandemic, throughout various disciplines
and countries.\textsuperscript{17} Furthermore, there are increasing
reports on higher hospital admission rates, indicating higher acuity
patients, with increased morbidity and mortality due to delayed medical
care in non-COVID-19 emergency conditions. \textsuperscript{18-20}

In this descriptive cross-sectional study, we compare three parallel
time periods during two consecutive years, and show a significant
decrease in pediatric asthma related ED visits during COVID-19 lockdown.
Similar trends in asthma related ED visits were observed in different
countries, and possible explanations were suggested by the different
authors \textsuperscript{11,21-24}. Since the major triggers for asthma
exacerbation in the pediatric population are viral infections, it was
expected that social distancing measures during lockdown will decrease
viral infections transmission, including Influenza virus, Rhinovirus and
Respiratory syncytial virus (RSV)\textsuperscript{25, 26} . Another
important trigger is outdoor exposure to pollen allergens and air
pollution\textsuperscript{27}, again substantially reduced due to
minimal exposure during lockdown and the reduction of industrial
work\textsuperscript{28}. Reduced physical activity during lockdown was
described in large questionnaires studies, along with an increase in
children's psychological and behavioral symptoms and elevated
screen-time\textsuperscript{29-31}. Socio-affective complications and
insufficient physical activity were underscored as two of the main
concerns, particularly among socio-economic deprived
children\textsuperscript{32}. As a result, a reduction in physical
activities reduces the number of asthma exacerbations related to
exercise induced bronchospasm (EIB) and exercise induced asthma (EIA).
The fewer ED visits during lockdown can also result from better asthma
control while the parents are at home, providing better adherence to
anti asthmatic controllers therapy\textsuperscript{33}. Although, this
issue is most probably of limited effect, since most of the parents that
participated in a telephone visit during lockdown, stated they stopped
the preventive therapy as their child was feeling well. Another issue
that should be discussed is the avoidance of approaching for medical
care during lockdown, due to concerns of parents from increased exposure
and the risk of COVID-19 transmission.

After lockdown, we demonstrated significant rise in number of ED visits,
even in comparison to same time period during the previous year. We
speculate this rise represents the return to routine activity with
everyday exposure to classmates, outdoor pollen exposure, rise in air
pollution and physical activity. This may resemble ''September
pandemic'', when children returning to school after summer vacations
with significant rise in asthma exacerbations\textsuperscript{8}.

Alongside with a significant reduction in ED visits for asthma
exacerbations during lockdown, higher hospitalization rates and longer
LOS were observed, that may indicate more severe exacerbations
predominate this period. This observation could be attributed to delay
in presentation both due to reduced availability of community medical
services during lockdown and transition towards telemedicine-based
practice as well as the hesitation to come to the ED due to the fear to
contract COVID-19. Our data indicated that hospitalization rate was 1.5
times higher during lockdown period compared to the previous year, in
contrary to other publications that reported a reduction in the number
of hospitalizations in the pediatric population during this
period\textsuperscript{23,34}. We believe this fact is related to
different demographics between countries, with majority of Bedouin Arab
population in our region. Another possible explanation for the higher
admission rate and longer LOS seen during lockdown could be a lower
threshold for admission at the ER and higher threshold for discharging
the patient from the wards, in light of the reduced availability of
community health care services and the concern of lack of proper
follow-up in the community.

Our study has a few limitations. This is a single tertiary center
experience, and therefore can be influenced, as mentioned, by the unique
demographics in the region. Another limitation is the retrospective
nature of our study, with all data drawn from electronic files. Some of
the data that was documented in a hard copy, in extremely acute patients
treated in the resuscitation room, may be missing in the electronic
files (e.g. intravenous Magnesium Sulfate).

In conclusion , we report a new pattern of ED visits and hospital stay
of children with asthma related symptoms, associated with the COVID-19
pandemic, that perhaps is not only confined to asthma. Pediatricians
should be aware to this phenomenon at the community and hospital levels.

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