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\begin{document}

\title{ASTHMA MIGHT PROTECT AGAINST MORTALITY IN CHILDREN HOSPITALIZED WITH
COVID-19}



\author[1]{Braian Sousa}%
\author[1]{Paulo Mai}%
\author[1]{Sandra Vieira}%
\author[1]{Antonio Pastorino}%
\author[2]{Alexandre Ferraro}%
\affil[1]{Universidade de Sao Paulo Faculdade de Medicina}%
\affil[2]{Universidade de Sao Paulo}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\textbf{ASTHMA MIGHT PROTECT AGAINST MORTALITY IN CHILDREN HOSPITALIZED
WITH COVID-19}

Braian Lucas Aguiar Sousa, MD

University of S\selectlanguage{ngerman}ão Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

Paulo Victor Ferreira Mai, MD

University of São Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

Sandra Elisabete Vieira, MD, PhD

University of São Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

Antonio Carlos Pastorino, MD, PhD

University of São Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

Alexandre Archanjo Ferraro, MD, PhD

University of São Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

\textbf{Running title:} Asthma might protect against COVID-19 mortality.

\textbf{Corresponding Author:}

Braian Lucas Aguiar Sousa, MD

Av Dr Eneas Carvalho de Aguiar, 647. São Paulo -- Brazil

Braian.sousa@usp.br/braianlucas@gmail.com

\textbf{Word count:} 1196

\textbf{Number of tables:} 2

\textbf{Number of figures:} 0

\textbf{ASTHMA MIGHT PROTECT AGAINST MORTALITY IN CHILDREN HOSPITALIZED
WITH COVID-19}

To the Editor,

The COVID-19 pandemic has been the greatest health challenge of the
century, claiming the lives of over five million people so far.
Fortunately, children and adolescents have been relatively spared, with
most of the deaths being among the eldest and those with preexisting
medical conditions. However, pediatric COVID-19 morbidity and mortality
are possible, especially among clinically and/or socioeconomically
vulnerable patients. Multiple studies have reported the risk associated
with specific previous comorbidities that might increase the odds of
adverse outcomes.\textsuperscript{1} Asthma is one of the most common
chronic diseases of childhood. The role played by the condition on the
outcomes of pediatric COVID-19 patients is still up for discussion. To
add to the debate, we have performed a large retrospective analysis of
pediatric COVID-19 patients hospitalized in Brazil, up to September
2021.

We have extracted data from the SIVEP-Gripe database, a national
surveillance databank that records data from all hospitalized patients
with severe acute respiratory infections, including COVID-19. The
notification is mandatory, and each observation contains over 160 fields
with information including demographic characteristics (like age, sex,
self or parent-reported race, municipality of residence), clinical
presentation, self or parent-reported comorbidities, etiological
investigation, and outcomes. We have included all patients with ages
ranging from 5 to 20 years, hospitalized, with COVID-19 infection
confirmed either by a positive PCR, positive antigen test, or positive
IgM test. Patients without a defined final outcome (discharge or death)
by September 6\textsuperscript{th}, 2021 were excluded. After describing
the sociodemographic characteristics and clinical outcomes of asthmatic
and non-asthmatic patients, we studied the association of asthma with
three possible outcomes: pediatric intensive care unit (PICU) admission,
use of invasive ventilatory support (IVS), and in-hospital mortality. We
used multilevel mixed-effects generalized linear models (GLM) to
calculate de odds ratio (OR) between exposure and outcomes, assuming
municipality and health unit of hospitalization as random effects.

The analysis included 9,807 patients, 858 (8.7\%) of whom had a self or
parent-reported diagnosis of asthma. Table 1 compares the
sociodemographic characteristics and outcomes of asthmatic and
non-asthmatic patients. When compared to asthmatic patients, a higher
proportion of non-asthmatic children lived in the northern half of the
country and were female. They also had more comorbidities and were
older. As for the outcomes, there was no difference among the groups in
PICU admission and IVS. Ten percent of non-asthmatic children died,
while for asthmatics this number was only 6.4\% (p=0.001).

Table 2 shows the risk of adverse outcomes for asthmatic patients taking
non-asthmatic children as reference, and stratifying for age. For
children from 5 to 10 years, asthma lowers the risk of death by 56\%
(95\%CI 0.20-0.97) on the adjusted model. For all other outcomes and age
groups, the condition does not significantly affect the outcomes,
although there is a tendency to offer a higher risk of PICU admission
among adolescents on the adjusted model (OR 1.28 95\%CI 0.98-1.67).

This analysis is one of the largest performed in Brazil to study the
role of asthma in COVID-19 pediatric patients. We have found that for
children aged 5 to 10 years, a previous diagnosis of asthma might be a
protective factor for mortality, reducing the odds of death by 60\%. For
adolescents, and for other outcomes like PICU admission and use of IVS,
there seems to be no association between exposure and outcome.

Asthma is one of the most important risk factors for morbidity in
respiratory infectious diseases.\textsuperscript{2} Therefore, it is odd
to find the condition not associated with poor outcomes in COVID-19
patients. However, these results are not unique in the literature. In a
metanalysis by Sunjaya et al., including more than 965,000 COVID-19
patients of all ages, asthma was not a risk factor for ICU admission,
ventilator use, and mortality.\textsuperscript{3} Harwood et al.
included 21,412 children in a metanalysis that found asthma to reduce
the odds of admission to critical care and
mortality.\textsuperscript{4}The study is published as a preprint,
pending peer-review. Putting our results together with previous
findings, it is coming clear that indeed asthma is not a risk factor for
poor outcomes in COVID-19 children and adolescents, and might protect
against some of them.

The main paths by which asthma and other allergic diseases might confer
protection against COVID-19 morbidity and mortality are still up for
discussion, but the role of the type of asthma phenotype is among the
main hypotheses. Current knowledge classifies the pathogenesis of asthma
into type 2 (T2) high and T2-low, with a predominance of eosinophilic
inflammation in the former, and a predominance of neutrophils in the
latter.\textsuperscript{5} The predominance of T2-high allergic asthma
among children is well known, reaching up to 80\% of the cases and being
more responsive to corticosteroids, while in adults with obesity and
without allergic sensitization, T2-low asthma predominates with little
action of corticosteroids.\textsuperscript{6} Recently the cytokines
IL-4 and IL-13, more expressed in T2-high phenotype, were demonstrated
to reduce the expression of the angiotensin 2 receptor (ACE2) in the
airway epithelial cells, the gateway for the SARS-COV-2 virus. On the
other hand, the cytokines IL-12, IL-17, and TNF can increase the
expression of ACE2 in T2-low asthmatics and in chronic obstructive
pulmonary disease patients.\textsuperscript{7,8}

Another finding that has intrigued researchers is the role of
eosinophils in COVID-19 patients with an allergic T2-high profile.
Previously recognized only in responses to helminths and allergic
diseases, eosinophils are currently known to have effector functions,
especially in the digestive tract and airways, releasing cytokines and
mediators that promote immunoregulation and antiviral
activity.\textsuperscript{9} Furthermore, many reports have shown the
potential effects of eosinophils during the COVID-19 pandemic: absence
of eosinophils on the first day of hospitalization in non-asthmatic
patients is associated with worse prognosis\textsuperscript{10},
patients with a low number of eosinophils require longer
hospitalizations and an increase in eosinophils is associated with
COVID-19 improvement and hospital discharge.\textsuperscript{11}

The main limitations of this study are related to its reliance on
secondary data. Case ascertainment bias is a possibility, as is
underreporting. There is also a considerable rate of missingness for
some characteristics, especially ethnicity. Notably, the asthma
diagnosis is self or parent-reported, without objective parameters like
spirometry or an in-depth clinical evaluation. This leads to a
considerable degree of subjectivity, as a previous history of recurrent
wheezing might be reported as asthma, for instance. This also justified
the age group chosen for analysis, since before 5 years of age, wheezing
episodes could be more related to viral conditions. On the other hand, a
fair amount of underdiagnosis is expected, especially in regions with a
higher socioeconomic vulnerability and lower health care access. It is
also important to note that among all the comorbidities reported in the
database, asthma is the only one that confers protection against
mortality, with all of the others tending to confer risk, as previously
showed by our group.

In conclusion, we have described the role of asthma on the outcomes of
hospitalized children and adolescents with COVID-19 in Brazil. In this
population, the disease is not a risk factor for PICU admission and use
of IVS, and protects against mortality among children. Considering that
asthma is one of the most common chronic diseases of childhood, these
findings are important for public health measures concerning school
reopening and vaccination.

Braian Lucas Aguiar Sousa, MD

University of São Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

Paulo Victor Ferreira Mai, MD

University of São Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

Sandra Elisabete Vieira, MD, PhD

University of São Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

Antonio Carlos Pastorino, MD, PhD

University of São Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

Alexandre Archanjo Ferraro, MD, PhD

University of São Paulo School of Medicine -- Department of Pediatrics.
Sao Paulo, Brazil.

\textbf{REFERENCES:}

1-Sousa BLA, Brentani A, Costa Ribeiro CC, et al. Non-communicable
diseases, sociodemographic vulnerability and the risk of mortality in
hospitalised children and adolescents with COVID-19 in Brazil: a
cross-sectional observational study. BMJ Open. 2021;11(9):e050724.

2- Juhn YJ. Risks for infection in patients with asthma (or other atopic
conditions): is asthma more than a chronic airway disease?. J Allergy
Clin Immunol. 2014;134(2):247-259.

3- Sunjaya AP, Allida SM, Di Tanna GL, Jenkins CR. Asthma and
Coronavirus Disease 2019 Risk: a systematic review and meta-analysis
{[}published online ahead of print, 2021 Aug 24{]}. Eur Respir J.
2021;2101209.

4- Harwood R, Yan H, Talawila Da Camara N, et al. Which children and
young people are at higher risk of severe disease and death after
SARS-CoV-2 infection: a systematic review and individual patient
meta-analysis. MedRxiv 2021.06.30.21259763.

5- Coverstone AM, Seibold MA, Peters MC. Diagnosis and Management of
T2-High Asthma. J Allergy Clin Immunol Pract. 2020;8(2):442-450.

6- Fitzpatrick AM, Chipps BE, Holguin F, Woodruff PG. T2-''Low'' Asthma:
Overview and Management Strategies. J Allergy Clin Immunol Pract.
2020;8(2):452-463.

7- Kimura H, Francisco D, Conway M, et al. Type 2 inflammation modulates
ACE2 and TMPRSS2 in airway epithelial cells. J Allergy Clin Immunol.
2020;146(1):80-88.e8.

8- Song J, Zeng M, Wang H, et al. Distinct effects of asthma and COPD
comorbidity on disease expression and outcome in patients with COVID-19.
Allergy. 2021;76(2):483-496.

9- Lindsley AW, Schwartz JT, Rothenberg ME. Eosinophil responses during
COVID-19 infections and coronavirus vaccination. J Allergy Clin Immunol.
2020;146(1):1-7.

10- Tanni F, Akker E, Zaman MM, Figueroa N, Tharian B, Hupart KH.
Eosinopenia and COVID-19 {[}published online ahead of print, 2020 Jul
16{]}. J Am Osteopath Assoc. 2020;10.7556/jaoa.2020.091.

11- Xie G, Ding F, Han L, Yin D, Lu H, Zhang M. The role of peripheral
blood eosinophil counts in COVID-19 patients. Allergy.
2021;76(2):471-482.

\textbf{Keywords:} COVID-19, asthma, pediatrics, children, SARS-CoV-2,
epidemiology.\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Asthmatic} \textbf{(N=858)}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Asthmatic} \textbf{(N=858)}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Non-Asthmatic (N=8,949)}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Non-Asthmatic (N=8,949)}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{Characteristic}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{Categories}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{N}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{\%}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{N}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{\%}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{p-value}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Region\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
North\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
247\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
28.8\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
3,008\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
33.6\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.004\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Age\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
5-10yrs\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
386\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
45\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2,117\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
23.7\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
10-15yrs\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
213\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
24.8\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2,071\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
23.1\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
15-20yrs\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
259\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
30.2\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4,761\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
53.2\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Sex\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
445\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
51.9\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4,275\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
47.8\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.022\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Ethnicity\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Non-White\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
388\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
54.6\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4,202\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
57.2\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.195\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
NCDs\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
With other NCDs\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
260\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
30.3\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
3,284\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
36.7\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
PICU Admission\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
246\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
30.6\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2,352\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
28.9\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.311\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
IVS\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
99\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
12.6\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
990\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
12.7\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.904\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Death\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
55\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
6.4\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
898\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
10\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Table 1: \textbf{Sociodemographic characteristics and clinical outcomes
of asthmatic and non-asthmatic patients.} Frequencies are number (N) and
percentages (\%). NCDs: noncommunicable diseases; PICU: pediatric
intensive care unit; IVS: invasive ventilatory support. p: chi-square
test.\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Crude model}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Crude model}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Crude model}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Adjusted model}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Adjusted model}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Adjusted model}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Outcomes}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Category}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{OR}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{95\%CI}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{p}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{OR}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{95\%CI}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{p}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
PICU 5-10yo\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Non-Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.96\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.72-1.29\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.81\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.09\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.79-1.51\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.58\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
PICU 10-20yo\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Non-Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.09\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.85-1.39\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.49\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.28\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.98-1.67\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.07\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
IVS 5-10yo\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Non-Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.75\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.50-1.12\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.17\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.88\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.56-1.39\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.59\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
IVS 10-20yo\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Non-Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.22\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.90-1.64\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.20\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.31\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.95-1.81\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.10\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Death 5-10yo\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Non-Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.43\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.21-0.88\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.02\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.44\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.20-0.97\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.04\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Death 10-20yo\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Non-Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Asthmatic\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.80\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.56-1.14\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.22\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.89\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.60-1.32\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.56\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Table 2: \textbf{Comparison of risk for severe outcomes in asthmatic and
non-asthmatic patients.} Results of multilevel mixed-effects generalized
linear models, with municipality and hospital as random effects Models
adjusted for sex, age group, region, ethnicity and presence of other
comorbidities. YO: years old. PICU: pediatric intensive care unit; IVS:
invasive ventilatory support; OR: odds ratio; 95\%CI: 95\% confidence
interval.

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