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\begin{document}

\title{Impact of the COVID-19 Pandemic on Pediatric Cystic Fibrosis Pulmonary
Exacerbations}



\author[1]{Shreya Patel}%
\author[1]{Misty Thompson}%
\author[2]{James Slaven}%
\author[1]{Don Sanders}%
\author[3]{Clement Ren}%
\affil[1]{Indiana University School of Medicine}%
\affil[2]{Indiana University Purdue University at Indianapolis}%
\affil[3]{Indiana University System}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\begin{abstract}
To assess the impact of COVID-19 restrictions on cystic fibrosis (CF)
pulmonary exacerbations (PEx) we performed a retrospective review of PEx
events at our CF Center and compared the rate of PEx in 2019 vs 2020.
Restrictions on social interaction due to the COVID-19 pandemic were
associated with a lower rate of PEx at our pediatric CF Center,
suggesting that these restrictions also reduced exposure to other
respiratory viral infection in children with CF.%
\end{abstract}%



\sloppy


Impact of the COVID-19 Pandemic on Pediatric Cystic Fibrosis Pulmonary
Exacerbations

Shreya Patel BS\textsuperscript{1}, Misty D Thompson
BS\textsuperscript{2,3}, James E. Slaven MS\textsuperscript{4}, Don B.
Sanders MD MS\textsuperscript{2,3}, and Clement L. Ren MD
MBA\textsuperscript{2,3}

\textsuperscript{1} Indiana University School of Medicine, Indianapolis,
IN USA

\textsuperscript{2} Division of Pediatric Pulmonology, Allergy, and
Sleep Medicine, Riley Hospital for Children, Indianapolis, IN USA

\textsuperscript{3} Department of Pediatrics, Indiana University School
of Medicine, Indianapolis, IN USA

\textsuperscript{4} Department of Biostatistics, Indiana
University/Purdue University at Indianapolis, IN USA

Correspondence to:

Clement L. Ren, MD, MBA

Division of Pediatric Pulmonology, Allergy, and Sleep Medicine

Riley Hospital for Children

ROC 4270

705 Riley Hospital Drive

Indianapolis, IN 46202

Phone: 317-948-7180

FAX: 317-944-7247

Email: clren@iu.edu

Keywords: cystic fibrosis, exacerbation, COVID-19, epidemiology

Acknowledgements: S. Patel was supported by NIH T35HL110854.

Abstract:

To assess the impact of COVID-19 restrictions on cystic fibrosis (CF)
pulmonary exacerbations (PEx) we performed a retrospective review of PEx
events at our CF Center and compared the rate of PEx in 2019 vs 2020.
Restrictions on social interaction due to the COVID-19 pandemic were
associated with a lower rate of PEx at our pediatric CF Center,
suggesting that these restrictions also reduced exposure to other
respiratory viral infection in children with CF.

To The Editor:

The COVID-19 pandemic resulted in widespread restrictions on social
interactions and lockdowns in many areas of the world {[}1{]}. The
impact of these measures on cystic fibrosis (CF) pulmonary exacerbations
(PEx) has not been described. Respiratory viral infections are a common
trigger for PEx {[}2, 3{]}, and COVID-19 restrictions might lead to
fewer PEx by reducing exposure to viruses in general, not just
SARS-CoV2. To test the hypothesis that the COVID-19 lockdown would be
associated with a lower PEx incidence we compared PEx data at our CF
Center from the time with the most stringent restrictions in Indiana to
the same time interval in 2019.

We identified PEx events by performing a retrospective chart review of
children with CF followed at the CF Center at Riley Hospital for
Children. We limited the age range to 2-11 years to avoid any potential
confounding by elexacaftor/tezacaftor/ivacaftor therapy {[}4, 5{]}. We
collected data from two time intervals in both 2019 and 2020: January 1
to March 15 (which corresponded to the months prior to the COVID-19
detection in Indiana) and March 16 to May 15 (which corresponded with
the months of peak COVID-19 incidence in 2020). PEx was determined by
the treating clinician based on changes in signs, symptoms, and/or lung
function. Every PEx event was analyzed during these timeframes, and data
collected included demographics, height and weight, lung function,
microbiology, location of encounter, and antibiotic treatment. Data were
analyzed using descriptive statistics and generalized linear models
where data had repeated measures. This project was reviewed and approved
by our local institutional review board prior to data collection.

The number and location of PEx events during the time intervals studies
are shown in the Table. The number of PEx events were significantly
decreased in both time intervals in 2020 compared to 2019, although the
decline was even greater from March 16 to May 15. The location of
patients' PEx events also differed between 2019 and 2020, with a
significantly lower percentage of PEx occurring through in-person clinic
visits and a much larger percentage occurring through phone encounters.
The number of patients (80 in 2019 and 78 in 2020) and their clinical
characteristics, such as sex, genotype, respiratory culture history,
baseline lung function, and nutritional indices were similar for both
years, suggesting that our observations were not due to an overall
improvement in the health of our patients. However, whereas 100\% of
clinic visits in 2019 and from January 1-March 16 2020 were in-person,
only 16\% of visits during the March 16-May 15 2020 time interval were
in-person.

Our analysis shows that COVID-19 restrictions were associated with
decreased PEx events and a shift towards PEx diagnosis through phone
encounters rather than in-person visits. We speculate that this may have
occurred due to reduced exposure to respiratory viral infections in
general. It is also possible that because our patients and their parents
were both at home more, there was improved adherence. We also observed a
reduction in PEx rate prior to March 16, which may reflect the fact that
patients were already engaging in a degree of self-isolation prior to
the statewide lockdown. The decrease in in-person PEx events reflects
the increased use of telehealth at the height of the COVID-19 pandemic
in Indiana. Limitations of our analysis include the retrospective study
design and the fact that we only analyzed data from a single CF Center.

In summary, restrictions on social interaction due to the COVID-19
pandemic were associated with a lower rate of PEx at our pediatric CF
Center. These results are consistent with other studies demonstrating
the importance of respiratory viral infections as a trigger for PEx and
will help CF clinician anticipate the burden of CF lung disease should
severe lockdowns due to COVID-19 occur again in their region.

References:

1. Studdert DM, and Hall MA. Disease Control, Civil Liberties, and Mass
Testing --- Calibrating Restrictions during the Covid-19 Pandemic. New
Engl J Med. 2020;383:102-4.

2. Meyer VMC, Siqueira MM, Costa P, Caetano BC, Oliveira Lopes JC,
Folescu TW, et al. Clinical impact of respiratory virus in pulmonary
exacerbations of children with Cystic Fibrosis. PLoS One.
2020;15:e0240452.

3. Wat D, Gelder C, Hibbitts S, Cafferty F, Bowler I, Pierrepoint M, et
al. The role of respiratory viruses in cystic fibrosis. J Cyst Fibros.
2008;7:320-8.

4. Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis
E, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus
ivacaftor combination regimen in people with cystic fibrosis homozygous
for the F508del mutation: a double-blind, randomised, phase 3 trial.
Lancet. 2019;394:1940-8.

5. Middleton PG, Mall MA, Drevinek P, Lands LC, McKone EF, Polineni D,
et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a
Single Phe508del Allele. N Engl J Med. 2019;381:1809-19.

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