\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{The role of red blood cells exchange in Sickle cell disease in a patient
with COVID-19 infection and pulmonary infiltrates. (Case report and
mini-review)}



\author[1,1]{Lina Okar}%
\author[1]{Maya aldeeb}%
\author[1]{Mohamed yassin}%
\affil[1]{Hamad Medical Corporation}%


\vspace{-1em}



  
  \date{June 12, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
COVID-19 related pneumonia overlaps with ACS, one of the most common
acute presentations in SCD patients.We present a case of 22-year-old SCD
patient presented to the emergency department with mild respiratory
symptoms turned out to be COVID-19 positive and received red blood cell
exchange to avoid the possibility of deterioration.%
\end{abstract}%



\sloppy


\textbf{Introduction:}

COVID-19 also known as severe acute respiratory syndrome coronavirus 2
(SARS-COV2) is the novel virus that caused the latest pandemic in the
world. The most serious presentation of this virus was acute respiratory
distress syndrome (ARDS) which has high mortality rate. Elderly patient
and those with multiple co-morbidities have been categorized as
high-risk group for developing serious complication from COVID-19
infection{[}1{]}.

SCD is one of the most common hemoglobinopathies worldwide, it affects
the shape of Red Blood Cells (RBCs) which leads to several clinical
manifestations. Complications might be acute or chronic, the most
important and common acute complications are Vaso-occlusive crisis (VOC)
and Acute Chest Syndrome (ACS){[}2{]}. Respiratory infections are
considered an important trigger for ACS{[}3{]}. The impact of COVID-19
infection in SCD patients is still not clear and data is conflicting.
However, some experiences suggested low mortality and morbidity rate in
SCD patients with COVID-19 infection{[}4{]}. previously published
researches mentioned the overlap between COVID-19 pneumonia and
ACS{[}1{]} which we believed rises a challenge for physician, thus we
recommend that those patients should monitored closely as deterioration
in their clinical status was prescribed in multiple case reports{[}5{]}.
The definitive management plan in this situation is not defined clearly
till now. Whether applying early red blood cells exchange can prevent
further deterioration is still a question that need to be answered.

\textbf{Case presentation:}

A 22-year-old male presented to the hospital with history of fever, sore
throat, mild nonproductive cough, generalized body ache, chest pain,
fatigue, and decreased appetite for three days. Positive sick contact
history with an a positive COVID-19 case, no recent travel. His past
medical history was remarkable for non-transfusion dependent Sickle cell
disease taking Hydroxyurea 500 mg daily, no previous surgeries, previous
recurrent painful crisis most of them did not require hospital admission
and presented as generalized pain, pain in the right arm and left hip
which appeared to be avascular necrosis, last painful crisis was 7
months before as lower limb pain relieved with tramadol . Primary
investigations including Laboratory tests, Nasopharyngeal swab for
COVID-19 PCR, chest Xray were performed and the result were as
following: Table.1

To this point the patient differential diagnosis was: Acute chest
syndrome triggered with COVDI-19 infection or viral pneumonitis. He
admitted to the intensive care unit (ICU) after considering him as high
risk for COVID-19 complication. The decision was made to do red blood
cells exchange early in the course of the infection to avoid possible
deterioration in his case and the need of intubation. Upon admission to
the ICU his vital were as following: Temperature 36.4, Heart rate
69/min, Respiratory rate 20/ min, Blood pressure 117/59 mmHg, maintain
oxygen saturation of 96\% on room air, he didn't require any oxygen
supplementation in ICU. He was on the following medications: Lopinavir/
Ritonavir (Kaletra) 200/50 mg for two days then stopped and cefuroxime
1.5 g daily for 7 days, Hydroxyurea 500 mg daily, enoxaparin 40 mg SC as
thrombosis prophylaxis though he had Thrombocytopenia which is relative
contraindication as well he is high risk of thromboembolic in SCD.
Plasma exchange with 6 units PRBCs was done on the second day of
hospital admission without any complications. He stayed in the ICU for 4
days for observation then transferred to the ward, during ICU admission
no deterioration was happened, in the ward repeated Chest X-ray was
normal. After 6 days in the ward without any deterioration in his
clinical course with resolving of respiratory symptoms the patient was
discharged to a quarantine facility.

\textbf{Discussion:}

Coronavirus is the novel virus responsible for the latest pandemic that
declared by World Health Organization WHO on March 11,2019. Taking a
good history to define the risk of infection is critical as patient
might be asymptomatic. However, symptomatic patients may present with
fever, dyspnea, fever, fatigue, and generalized muscle ache. Other
non-typical symptoms like gastrointestinal were also reported{[}6{]}.
Severity of the disease differs among affected patients, elderly,
patients with co-morbidities like hypertension, diabetes and
cardiovascular diseases are at more risk for complication and worse
clinical course than normal population{[}7{]}.

Sickle cell disease (SCD) is an inherited hemoglobinopathy with main
characteristic being the presence of Hemoglobin S (HbS). The inheritance
might be in homozygous or heterozygous form with a disease severity that
differs accordingly. This hemoglobin cause deformity in the structure of
Red Blood Cells (RBCs) changing them to sickle-shaped, rigid as well
dysfunctional RBCs. Clinical manifestations are Vaso-occlusive crisis
(VOC), intra- and extra- vascular hemolytic anemia {[}2{]}. Complication
of SCD can be categorized into acute and chronic.

Acute complications include: Acute chest syndrome (ACS), Vaso-occlusive
crisis (VOC), hepatobiliary complications, stroke, splenic
sequestration, priapism, acute anemia, and fever{[}8{]}. Chronic
complications are pulmonary hypertension, hepatic iron overload, kidney
disease, avascular necrosis, retinopathy, and legs ulcer {[}7,9--12{]}.
Among the acute complications, the most common are VOC and ACS. VOC are
episodes of severe pain due to microvascular occlusion with erythrocytes
and leukocytes, thus preventing blood flow and causing organ ischemia.
ACS is common lung insult in SCD patients, known as newly pulmonary
infiltrate due to alveolar consolidation affecting one lung segment at
least, in it is severe form it is similar to the acute respiratory
distress syndrome (ARDS), along with the radiological findings, patients
usually present with fever, chest pain, shortness of breath, cough and
wheezing. Its considered the second most common cause of hospitalization
and the main reason behind intensive care unit admission as well early
death among those patients{[}3{]}. There are three previously mentioned
causes of ACS; first: pulmonary infection, second: bone marrow fat
embolization and thirdly, intra-vascular pulmonary sequestration. Among
those causes, pulmonary infections are the most common one and it is
usually due to community-acquired pathogen that cause over inflammatory
response instead of mild upper respiratory picture{[}3{]}. The National
Acute Chest Syndrome Study published by Vichinsky et al to defined the
causes of ACS, their study showed that infections are the main cause
with atypical bacteria and viruses being the major causes, and despite
the splenic dysfunction in SCD encapsulated bacteria were rarely
isolated{[}13{]}.

Patients with hemoglobinopathies are considered high risk for developing
severe complication from COVID-19 infection as per the Thalassemia
international federation{[}14{]}.However, no strong evidence is
available, and it is not known in COVID-19 infection really increase the
morbidity and mortality in SCD patients or not{[}4{]}. The overlap
between the ACS and COVID-19 pneumonia has been described {[}15{]}.
Thus, taking a final decision in this regard is hard because of the
conflict in literature and variance of COVID-19 clinical course among
SCD population, we summarize all previously published data in Table 2.

As we notice from the table above few published cases described the use
of RBCs exchange to manage ACS in SCD patients. Whenever RBCs exchange
was used it was because the patients deteriorated, interestingly all of
them improved after the exchange that is why we should raise the
following question `` is it necessary to leave this choice as a rescue
option?'' . The most similar published case to our patient was published
by and described the role of early RBCs exchange in preventing further
deterioration in their patient as once oxygen requirement started to
increase RBCs exchange offered rather than simple transfusion or other
medications{[}15{]}. The difference in our case is that we chose to
offer our patient RBCs exchange even when he was stable due to the
overlapping between ACS and COVID-19 pneumonia and by weighing the
benefit and risk we believe that giving him RBCs exchange played an
important role in alleviating the infection course as well the need of
ICU admission and possible intubation.

Both pneumonia and acute chest syndrome are life-threatening condition.
Red blood cell exchange is well known method to treat ACS and there are
published data about using it in case of severe COVID-19 pneumonia,
mostly after deterioration {[}1,5,15{]}. Here, we present the first case
report for SCD patient infected with COVID-19 who received red blood
cells exchange immediately after admission to avoid the deterioration
and need of intubation giving him the benefit of doubt. We think
offering RBCs exchange for patients with SCD and COVID-19 pneumonia upon
diagnosis may have major benefits such as, avoiding ICU admission and
intubation.

\textbf{Conclusion:}

With the latest pandemic due to COVID-19 infection a lot of patients
were vulnerable and at risk of developing severe and fatal
complications. Patients with SCD suffer from multiple acute and chronic
complications. The exact clinical course of COVID-19 infection in those
patients is not yet final and conflicting data are available. However,
delaying appropriate management may carry an increased risk for
intubation and mortality. We recommend that physicians should keep a low
threshold for admitting SCD patients in whom they suspect COVID-19
infection and to monitor them closely as well provide RBCs exchange
initially in the disease course to give them the benefit of doubt. More
research is needed to reach a high evidence regarding the management
plan.

\textbf{Acknowledgment}

We would like to acknowledge the Hematology section/ oncology
department, Intensive care unit as well as Family medicine residency
program at Hamad Medical Corporation for their support.

\textbf{Statement of Ethics}

Consent was obtained from the patients.

Case approved by HMC Medical Research center

\textbf{Declaration of interest}

The authors report no conflicts of interest.

\textbf{Authors contribution:}

All authors contributed equally in writing the manuscript.

\textbf{References:}

{[}1{]} Hussain FA, Njoku FU, Saraf SL, Molokie RE, Gordeuk VR, Han J.
COVID-19 infection in patients with sickle cell disease. Br J Haematol
2020;189:851--2. https://doi.org/10.1111/bjh.16734.

{[}2{]} Pinto VM, Balocco M, Quintino S, Forni GL. Sickle cell disease:
a review for the internist. Intern Emerg Med 2019;14:1051--64.
https://doi.org/10.1007/s11739-019-02160-x.

{[}3{]} Gladwin MT, Vichinsky E. T 2254. Sci York 2009:2254--65.
https://doi.org/10.1164/rccm.201111-2082CI.

{[}4{]} Ramachandran P, Perisetti A, Kathirvelu B, Gajendran M, Ghanta
S, Onukogu I, et al. Low morbidity and mortality with COVID-19 in sickle
cell disease: A single center experience. EJHaem 2020:jha2.87.
https://doi.org/10.1002/jha2.87.

{[}5{]} Beerkens F, John M, Puliafito B, Corbett V, Edwards C, Tremblay
D. COVID-19 pneumonia as a cause of acute chest syndrome in an adult
sickle cell patient. Am J Hematol 2020;95:E154--6.
https://doi.org/10.1002/ajh.25809.

{[}6{]} Down B, Kulkarni S, Khan AHA, Barker B, Tang I. Novel
coronavirus (COVID-19) infection: What a doctor on the frontline needs
to know. Ann Med Surg 2020;55:24--9.
https://doi.org/10.1016/j.amsu.2020.05.014.

{[}7{]} Soliman AT, Prabhakaran Nair A, Al Masalamani MS, De Sanctis V,
Abu Khattab MA, Alsaud AE, et al. Prevalence, clinical manifestations,
and biochemical data of type 2 diabetes mellitus versus nondiabetic
symptomatic patients with COVID-19: A comparative study. Acta Biomed
2020;91:e2020010. https://doi.org/10.23750/abm.v91i3.10214.

{[}8{]} Wali Y, Kini V, Yassin MA. Distribution of sickle cell disease
and assessment of risk factors based on transcranial Doppler values in
the Gulf region. Hematol (United Kingdom) 2020;25:55--62.
https://doi.org/10.1080/16078454.2020.1714113.

{[}9{]} Yassin M, Soliman A, De Sanctis V, Nashwan A, Abusamaan S,
Moustafa A, et al. Liver iron content (LIC) in adults with sickle cell
disease (SCD): Correlation with serum ferritin and liver enzymes
concentrations in transfusion dependent (TD-SCD) and non-transfusion
dependent (NT-SCD) patients. Mediterr J Hematol Infect Dis 2017;9.
https://doi.org/10.4084/mjhid.2017.037.

{[}10{]} Yassin MA, Soliman AT, de Sanctis V, Abdula MAJ, Riaz LM, Ghori
FF, et al. Statural growth and prevalence of endocrinopathies in
relation to liver iron content (LIC) in adult patients with beta
thalassemia major (BTM) and sickle cell disease (SCD). Acta Biomed
2018;89:33--40. https://doi.org/10.23750/abm.v89i2-S.7085.

{[}11{]} Shier A, Abdelrazek M, Soliman A, De~Sanctis V, Elsayed A,
Abdulla M, et al. Short-Term Outcome and MRI Changes in Three Adult
Patients with Sickle Cell Disease and Aseptic Osteonecrosis after
Treatment with Hyperbaric Oxygen Therapy: A Preliminary Report. Case Rep
Oncol 2020;13:365--72. https://doi.org/10.1159/000506330.

{[}12{]} Abdelmahmuod E, Yassin MA, Ahmed M, Ali E. The Relationship
Between Sickle Cell Disease and Sudden Onset Sensorineural Deafness.
Cureus 2020. https://doi.org/10.7759/cureus.9413.

{[}13{]} Vichinsky EP, Neumayr LD, Earles AN, Williams R, Lennette ET,
Dean D, et al. Causes and outcomes of the acute chest syndrome in sickle
cell disease. N Engl J Med 2000;342:1855--65.
https://doi.org/10.1056/NEJM200006223422502.

{[}14{]} Farmakis D, Giakoumis A, Cannon L, Angastiniotis M, Eleftheriou
A. COVID-19 and thalassaemia: A position statement of the Thalassaemia
International Federation. Eur J Haematol 2020:1--9.
https://doi.org/10.1111/ejh.13476.

{[}15{]} Allison D, Campbell-Lee S, Crane J, Vidanovic V, Webb S,
Fraidenburg D, et al. Red blood cell exchange to avoid intubating a
COVID-19 positive patient with sickle cell disease? J Clin Apher
2020;35:378--81. https://doi.org/10.1002/jca.21809.

{[}16{]} Hussain FA, Njoku FU, Saraf SL, Molokie RE, Gordeuk VR, Han J.
COVID-19 infection in patients with sickle cell disease. Br J Haematol
2020;189:851--2. https://doi.org/10.1111/bjh.16734.

{[}17{]} Nur E, Gaartman AE, van Tuijn CFJ, Tang MW, Biemond BJ.
Vaso-occlusive crisis and acute chest syndrome in sickle cell disease
due to 2019 novel coronavirus disease (COVID-19). Am J Hematol
2020;95:725--6. https://doi.org/10.1002/ajh.25821.

{[}18{]} Beerkens F, John M, Puliafito B, Corbett V, Edwards C, Tremblay
D. COVID-19 pneumonia as a cause of acute chest syndrome in an adult
sickle cell patient. Am J Hematol 2020;95:E154--6.
https://doi.org/10.1002/ajh.25809.

{[}19{]} De Luna G, Habibi A, Deux JF, Colard M, Pham Hung d'Alexandry
d'Orengiani AL, Schlemmer F, et al. Rapid and severe Covid-19 pneumonia
with severe acute chest syndrome in a sickle cell patient successfully
treated with tocilizumab. Am J Hematol 2020;95:876--8.
https://doi.org/10.1002/ajh.25833.

{[}20{]} Allison D, Campbell-Lee S, Crane J, Vidanovic V, Webb S,
Fraidenburg D, et al. Red blood cell exchange to avoid intubating a
COVID-19 positive patient with sickle cell disease? J Clin Apher
2020;35:378--81. https://doi.org/10.1002/jca.21809.

{[}21{]} Justino CC, Campanharo FF, Augusto MN, Morais SC de, Figueiredo
MS. COVID-19 as a trigger of acute chest syndrome in a pregnant woman
with sickle cell anemia. Hematol Transfus Cell Ther 2020;42:212--4.
https://doi.org/10.1016/j.htct.2020.06.003.

{[}22{]} Quaresima M, Quaresima V, Naldini MM, Cirillo DM, Ferrari A,
Mazzi A, et al. Clinical management of a Nigerian patient affected by
sickle cell disease with rare blood group and persistent SARS-CoV-2
positivity. EJHaem 2020. https://doi.org/10.1002/jha2.53.

{[}23{]} Azerad M, Bayoudh F, Weber T, Minon J, Ketelslegers O, Hoyoux
M, et al. Sickle cell disease and COVID-19: Atypical presentations and
favorable outcomes. EJHaem 2020. https://doi.org/10.1002/jha2.74.

{[}24{]} Al-Hebshi A, Zolaly M, Alshengeti A, Al Qurainees G, Yamani S,
Hamdan N, et al. A Saudi family with sickle cell disease presented with
acute crises and COVID-19 infection. Pediatr Blood Cancer 2020;67.
https://doi.org/10.1002/pbc.28547.

{[}25{]} Arlet JB, de Luna G, Khimoud D, Odi\selectlanguage{ngerman}èvre MH, de Montalembert M,
Joseph L, et al. Prognosis of patients with sickle cell disease and
COVID-19: a French experience. Lancet Haematol 2020;7:e632--4.
https://doi.org/10.1016/S2352-3026(20)30204-0.

{[}26{]} McCloskey KA, Meenan J, Hall R, Tsitsikas DA. COVID-19
infection and sickle cell disease: a UK centre experience. Br J Haematol
2020;190:e57--8. https://doi.org/10.1111/bjh.16779.

{[}27{]} Balanchivadze N, Kudirka AA, Askar S, Almadhoun K, Kuriakose P,
Fadel R, et al. Impact of COVID-19 Infection on 24 Patients with Sickle
Cell Disease. One Center Urban Experience, Detroit, MI, USA. Hemoglobin
2020. https://doi.org/10.1080/03630269.2020.1797775.

{[}28{]} Panepinto JA, Brandow A, Mucalo L, Yusuf F, Singh A, Taylor B,
et al. Coronavirus Disease among Persons with Sickle Cell Disease,
United States, March 20-May 21, 2020. Emerg Infect Dis 2020;26.
https://doi.org/10.3201/eid2610.202792.

\textbf{List of figure and table legends:}

Figure 1. Chest Xray.

Table 1. Investigations.

Table 2. Literature review.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

