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\begin{document}

\title{ARDS in an ex-premature infant with bronchopulmonary dysplasia and
COVID-19}



\author[1]{Meena Kalyanaraman}%
\author[1]{Derrick McQueen}%
\author[1]{Kavita Morparia}%
\author[1]{Maria Bergel}%
\affil[1]{Newark Beth Israel Medical Center}%


\vspace{-1em}



  
  \date{May 04, 2024}


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\selectlanguage{english}
\begin{abstract}
SARS-CoV-2 infection has caused a pandemic which has resulted in more
severe disease in adults than children. We report an ex-premature infant
with bronchopulmonary dysplasia who developed COVID-19 associated severe
acute respiratory distress syndrome causing bradycardic cardiac arrest
and seizures.%
\end{abstract}%



\sloppy


\textbf{Title:} \textbf{ARDS in an ex-premature infant with
bronchopulmonary dysplasia and COVID-19}

\textbf{Author information:}

Meena Kalyanaraman, MD\textsuperscript{1}; Derrick McQueen
MD\textsuperscript{1}; Kavita Morparia MD\textsuperscript{1}; Maria
Bergel MD\textsuperscript{1}

\textbf{Author affiliation:}

1: Pediatric Critical Care Medicine

Children's Hospital of New Jersey at Newark Beth Israel Medical Center

\textbf{Corresponding author:}

Meena Kalyanaraman, MD

Associate Director, Pediatric Critical Care Medicine

Children's Hospital of New Jersey at Newark Beth Israel Medical Center

C-5, 201 Lyons Ave

Newark NJ 07112

Phone: 862-763-1742

Email: mkalyanaraman68@gmail.com; Meena.Kalyanaraman@rwjbh.org

Fax: 973-926-6452

\textbf{Financial assistance} : None \textbf{Conflicts of interest} :
None

\textbf{Key words not in title} : hypoxemia, cardiac arrest, seizures,
ventilation, prone

\textbf{ARDS in an ex-premature infant with bronchopulmonary dysplasia
and COVID-19}

\textbf{Abstract} : SARS-CoV-2 infection has caused a pandemic which has
resulted in more severe disease in adults than children. We report an
ex-premature infant with bronchopulmonary dysplasia who developed
COVID-19 associated severe acute respiratory distress syndrome causing
bradycardic cardiac arrest and seizures.

\textbf{Case report} :

Our institutional review board waived informed consent for publication
of this case. A four month old male infant with bronchopulmonary
dysplasia (BPD) born premature at 28 weeks gestation with very low birth
weight of 1.315kg, whose corrected age is 1 month, presented with severe
respiratory distress and seizures. He was on non-invasive positive
pressure ventilation for 90 days for respiratory distress syndrome at
birth complicated by human metapneumovirus pneumonia and apnea. Patient
had been sick for 5 days prior to admission with cough, nasal congestion
and increased work of breathing. He was cared for by his parents who
were sick with coronavirus disease (COVID-19) symptoms.

Patient presented to the emergency department of a referral hospital
lethargic, seizing and hypoxemic with saturation by pulse oximetry of
77\%. There was no history of fever, vomiting, diarrhea, rash or
decrease in oral intake. He deteriorated and had a bradycardic cardiac
arrest and was resuscitated. Initial arterial blood gas analysis was pH
7.20/pCO2 81 mm Hg/pO2 39 mm Hg/bicarbonate 25 mEq/L/base excess -6 on
1.0 fraction of inspired oxygen (FiO2) with PaO2/FiO2 ratio of 39 and
oxygenation index of 41 . Blood and urine cultures were obtained, broad
spectrum antibiotics and levetiracetam were started, fluid boluses were
given and chest radiograph (CXR) revealed bilateral opacities with
central predominance.

Upon arrival in our pediatric intensive care unit (PICU) he was placed
on the ventilator using synchronized intermittent mandatory
ventilation/pressure regulated volume control mode with FiO2 1.0,
positive end expiratory pressure 10cm water, tidal volume 55, Rate
40/minute, inspiratory time 0.7sec to maintain saturations greater than
90\%. Patient was sedated and placed on neuromuscular blockade. CXR
showed significant worsening of bilateral infiltrates. (Figure) Within
24 hours of hospitalization patient became more hypoxemic, inhaled
nitric oxide was started and within 36 hours patient's oxygen saturation
decreased to the 70s and patient was proned. Saturations improved and
FiO2 was weaned to 0.40 within 8 hours of proning. He was proned for
12-14 hours each day for 4 days.

Rapid real-time reverse transcription polymerase chain reaction test was
positive for COVID-19 on nasopharyngeal swab specimen and respiratory
viral pathogen panel did not reveal any other viral co-infections.
Initial white cell count was 19.6 x 10\textsuperscript{3}/mcL with 44\%
segmented neutrophils, 1\% bands, 48\% lymphocytes, and 6\% monocytes.
Hemoglobin was 10.5 g/dL and platelet count was 401 x
10\textsuperscript{3} /mcL which decreased in a few hours to 115 x
10\textsuperscript{3}/mcL. Prothrombin time (PT), partial thromboplastin
time (PTT) and international normalized ratio (INR) were slightly
increased at 13.9 seconds, 1.41 and 26.8 seconds respectively. Patient
received packed red blood cell transfusion, fresh frozen plasma and
vitamin K. C-reactive protein was elevated at 3.68mg/dL and
procalcitonin was high at 0.88 ng/ml. Blood urea nitrogen was 25mg/dL,
serum creatinine was 0.35mg/dL and serum sodium was 126 mmol/L and they
improved with volume resuscitation. Alanine transaminase (ALT) and
aspartate transaminase (AST) increased significantly from \textless{}120
unit/L (U/L) and \textless{}60 U/L to peak of 1505 U/L and 2297 U/L
respectively within 12 hours of hospitalization . These enzymes slowly
decreased over a period of 3 weeks to near normal values. Albumin
decreased from 3.8g/dL on admission to 2.1 g/dL in 24 hours . Video
electroencephalogram did not show seizures, head ultrasound revealed
normal study. Echocardiogram showed normal biventricular systolic
function. Patient received methylprednisolone and hydroxychloroquine.
Remdesivir was not approved by the manufacturer secondary to severe
transaminitis. Patient was extubated on hospital day (HD) 8. Patient
remained on non -- invasive positive pressure ventilation until HD 22 .
He was on supplemental oxygen via nasal cannula for another five days
and discharged to home on albuterol and budesonide nebulizers,
chlorothiazide, spironolactone, and levetiracetam. Patient was playful
and interactive at the time of discharge from our hospital.

\textbf{Discussion}

We report for the first time to our knowledge a case of COVID-19 acute
respiratory distress syndrome (ARDS) causing severe hypoxemia leading to
bradycardic cardiac arrest and seizures in an ex-premature infant with
comorbidity of bronchopulmonary dysplasia.

After the first detection of novel coronavirus 2019 (SARS-CoV-2) in
China in early December 2019 initial studies showed most children were
asymptomatic or had mild and moderate symptoms. (1) The percentage of
severe and critical cases in the pediatric patients with COVID-19 was
5.9\% compared to 18.5\% in adult patients. Admission rates to PICU
range from 9.7\% among infected children to 20\% of the hospitalized
patients. (2,3) ARDS has been reported in 3-5.8\% of all COVID19
patients and in about 60\% of patients requiring ICU care in adults and
children. Our patient met the Berlin criteria for severe ARDS with
PaO2/FiO2 ratio \textless{} 100. Our patient had worsening hypoxemia and
increased inflammatory markers of CRP and procalcitonin, low platelets
and initial acute kidney injury similar to that seen by Chao and
colleagues. (4) The severe transaminitis noted in our patient has not
been reported in the pediatric studies published thus far. Our patient
had several risk factors for impaired alveolarization and normal lung
growth after birth secondary to the prolonged need for oxygen,
non-invasive positive pressure ventilation and post-natal infection with
human metapneumovirus. (5) The abnormal lung development in our patient
put him at high risk for ARDS from COVID-19 that led to hypoxemic acute
respiratory failure, bradycardic cardiac arrest and seizures. In
conclusion, the various manifestations of COVID-19 in children are still
not entirely known. Pediatricians and pediatric critical care physicians
should be cognizant of the development of ARDS from SARS-CoV-2
infections in patients with comorbidity of prematurity and associated
chronic lung disease as the various factors that interfere with their
post natal lung development continue to be studied.

\textbf{References:}

1. Dong Y, Mo X., Hu Y et al. Epidemiological characteristics of 2143
pediatric patients with 2019 coronavirus disease in China.
Pediatrics\emph{.} 2020; https://doi.org/10.1542/peds.2020-0702

2. Tagarro A, Epalza C, Santos M, et al. Screening and Severity of
Coronavirus Disease 2019 (COVID-19) in Children in Madrid, Spain
{[}published online ahead of print, 2020 Apr 8{]}. JAMA Pediatr.
2020;10.1001/jamapediatrics.2020.1346.
doi:10.1001/jamapediatrics.2020.1346

3. DeBiasi RL, Song X, Delaney M et al. Severe COVID-19 in Children and
Young Adults in the Washington, DC Metropolitan Region. J Peds. May
2020. DOI: \url{https://doi.org/10.1016/j.jpeds.2020.05.007}

{\label{debiasi-rl-song-x-delaney-m-et-al.-severe-covid-19-in-children-and-young-adults-in-the-washington-dc-metropolitan-region.-j-peds.-may-2020.}}

4. Chao JY, Derespina KR, Herold BC et al. Clinical Characteristics and
Outcomes of Hospitalized and Critically Ill Children and Adolescents
with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical
Center in New York City. J Peds May 2020. DOI:
https://doi.org/10.1016/j.jpeds.2020.05.006

5.~O'Reilly M, Sozo F, Harding R. Impact of preterm birth and
bronchopulmonary dysplasia on the developing lung: long-term
consequences for respiratory health.~Clin Exp Pharmacol Physiol.~2013;
40: 765--773.

\textbf{Figure legend}

Figure: Multifocal bilateral lung infiltrates\selectlanguage{english}
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