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\begin{document}

\title{COVID-19 infection in an infant with cystic fibrosis: a case report and
possible therapeutic effect of hypertonic saline}



\author[1]{Seyed Javad  Seyedi}%
\author[2]{Hossein  Sadeghi}%
\author[1]{Hamid-Reza Kianifar}%
\author[1]{Abdolkarim Hamedi}%
\author[1]{Amin Saeidinia}%
\affil[1]{Mashhad University of Medical Sciences}%
\affil[2]{Columbia University Medical Center}%


\vspace{-1em}



  
  \date{June 11, 2024}


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\selectlanguage{english}
\begin{abstract}
Pulmonary infections represent the major causes of morbidity and
mortality in cystic fibrosis(CF). Here, we report a3-month old infant
with pancreatic insufficient CF was hospitalized with positive
RT-PCRtest for COVID-19. He was treated successfully. Hypertonic saline
can be hypothesized as a treatment regimen against COVID-19 infection
after further investigation%
\end{abstract}%



\sloppy


\textbf{Introduction}

The novel corona virus commonly known as COVID-19 has caused global
pandemic. As of April 9th, more than 1.65 million individuals are
affected with a death rate of 6\% {[}1{]}. However, not many cases of
serious COVID-19 cases have been reported in children. Angiotensin
converting enzyme II (ACE2) is the likely receptor for COVID-19. There
is speculation that children may have decreased binding ability to ACE2
as maturity and function is lower. This may explain the lower severity
in children. CF is an autosomal-recessive genetic disease. There have
not been any case reports of individuals with CF and COVID-19 {[}2{]}.
Here, we present a case of an infant with CF who recovered from COVID-19
infection after treatment with hydroxychloroquine and inhaled hypertonic
saline.

\textbf{Case Presentation}

A 3-month old male, the second child of a family with consanguineous
marriage, with pancreatic insufficient CF who was born at full term
gestation with birth weight of 3.25 kg status post two operations for
intestinal obstruction at 3 and 46 days of life. Sweat test were 98
mmol/L and 90 mmol/L. He was admitted because of fever, tachypnea and
hypoxia, with oxygen saturation of 78\% in room that increased to 97\%
on 4 L/min of oxygen via oxyhood. He weighed 3.5 kg. Lungs were
remarkable for bilateral crackles and presence of bilateral lower limb
edema. On admission, WBC was (16.9 x 109 )/L (21\% neutrophil, 62\%
lymphocyte and 10\% monocyte), Hb 9.4 g/L, platelet of (412 x 109 )/L.
Electrolytes and liver function tests were normal. Chest radiograph and
chest CT (Figure 1) showed patchy infiltrates and increased interstitial
markings bilaterally. EKG was normal with QT interval of 0.37. G6PD
level was normal. He was treated with Meropenem and Vancomycin until the
deep throat culture results showed Klebsiella pneumonia that was
sensitive to Meropenem. Vancomycin was discontinued. Hydroxychloroquine
was started at 3mg/kg/dose, twice a day for 10 days. On the third day of
admission, he was started on aerosolized Salbutemol and hypertonic
saline (5\%) three times a day with improvement in oxygen requirement
and his respiratory symptoms. After five days of inhalation therapy, his
clinical status improved with resolution of respiratory distress and
oxygen requirement. His bilateral lower limb edema was attributed to
hypoalbuminemia and treated with nutritional supplementation and
appropriate pancreatic enzyme dosing.

\textbf{Discussion}

COVID-19 has not significantly affected individuals with CF. Whether
there is one or combination of protective factors in CF such as medical
therapies related to CF, genetic, immunological or mucosal barrier from
thick secretions remains to be identified. Children with CF have
underlying lung disease that is associated with pulmonary exacerbation
by viral infections.

Previous studies have shown that salt can affect viruses. In a study by
Zhang et. al. {[}3{]}, high salt was identified as a crucial regulator
of signaling. In another study by Siber and Podgornik {[}4{]} the
influence of salt was shown on encapsidation of single- stranded viral
RNA molecules. This influence was also shown on double stranded RNA at
250 mM sodium chloride. 5\% hypertonic saline is equivalent to 0.85 mM
NaCl.

In a recent study of COVID-19 patients in China {[}5{]} who received
hydoxychloroquine, an antimalarial agent with anti-inflammatory and
immunomodulatory activities, showed the drug did not clear the patients
of the virus. The overall 28-day conversion rate was not different
between standard of care group and standard of care plus
hydroxychloroquine group.

\textbf{Conclusions}

In this report, we try to hypothesize that hypertonic saline may be
considered as a therapeutic option for COVID-19 after further
investigations and randomized studies.

\textbf{Conflict of interest}

There is no conflict of interest.

We declare that none of the authors listed on the manuscript are
employed by a government agency that has a primary function other than
research and/or education. None of the authors are submitting this
manuscript as an official representative or on behalf of the government.

\textbf{Acknowledgement}

All authors thank from nursing care system of Akbar hospital for
management of patients in COVID-19 cases.

\textbf{Key clinical message}

Children with CF have underlying lung disease that is associated with
pulmonary exacerbation by viral infections. We also proposed that
hypertonic saline might be considered as a therapeutic option for
COVID-19.

\textbf{Author contribution}

Dr. Seyed Javad Seyedi, Dr. Abdolkarim Hamedi, Dr. Amin Saeidinia and
Dr. Hamidreza Kianifar managed patients and written the first draft of
the manuscript. Dr. Amin Saeidinia and Dr. Hossein Sadeghi collected
patient's data and written the final version. All authors read and
approved final version.

\textbf{Data availability statement}

The data that support the findings of this study are available from the
corresponding author upon reasonable request.

\textbf{Patient consent}

The authors have confirmed that patient's consent have been signed and
collected in accordance with the journal's patient consent policy.

\textbf{Acknowledgement}

Apart of this article was published online in previous submission to
another journal which was rejected.

https://www.authorea.com/doi/pdf/10.22541/au.159181168.86705728

\textbf{References}

{[}1{]} Deb S, Majumdar M. A time series method to analyze incidence
pattern and estimate reproduction number of covid-19. 2020.

{[}2{]} Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS.
Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor:
molecular mechanisms and potential therapeutic target. Intensive care
medicine. 2020:1-5.

{[}3{]} Zhang W-C, Du L-J, Zheng X-J, Chen X-Q, Shi C, Chen B-Y, et al.
Elevated sodium chloride drives type I interferon signaling in
macrophages and increases antiviral resistance. Journal of Biological
Chemistry. 2018;293:1030-9.

{[}4{]} Siber A, Podgornik R. Influence of salt and viral protein charge
distribution on encapsidation of single-stranded viral RNA molecules.
2008.

{[}5{]} Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al.
Hydroxychloroquine in patients with COVID-19: an open-label, randomized,
controlled trial. 2020.

Figure legend

Figure1- Lung CT scan demonstrating patchy infiltrates and increased
interstitial markings bilaterally\selectlanguage{english}
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