Discussion:
Coronavirus family has multiple strain, the latest novel virus caused
the coronavirus disease 2019 (COVID-19) was called severe acute
respiratory syndrome coronavirus 2 (SARS-CoV2)[8]. Data suggested
that this new virus acts through specific receptors on the erythrocytes
including ACE2, CD147 and CD26 causing pathological interaction with
hemoglobin molecule and sometimes resulting in hemolysis[9].
Sickle cell disease (SCD) is a common inherited hemoglobinopathy. It is
due to a single amino acid substitution in the sixth residue of beta
globin subunit, this pathological change results in hemoglobin S (HBS).
HBS is an abnormal hemoglobin that causes structure deformity in red
blood cells (RBCs) changing it to crescent or sickle shape[10].
SCD complications are categorized into acute and chronic. The acute
presentations are described as time-dependent which mean there should be
high suspension to diagnose them early and offer appropriate evaluation
and treatment, thus improving the prognosis. These complications include
ACS, vaso-oclusive crisis (VOC), acute anemia, hepatobiliary
complications, Stroke, splenic sequestration, and priapism. Whereas
chronic complications are pulmonary hypertension, hepatopathy due to
iron overload, avascular necrosis, retinopathy, renal disease and
peripheral ulcers [10].
Hemolytic crisis is defined as drop of more than or equal to 2 g/dL from
the baseline patient’s hemoglobin value. Acute anemia might present as a
single presentation or in accordance with splenomegaly or hepatomegaly
[10]. However, when aplastic crisis diagnosis is made it is
essential to rule out any possibility of delayed hemolytic transfusion
reaction as more cautions is required if RBCs transfusion is the
plan[1].
ACS is the most cause of hospital admission and mortality among SCD
patients. The trigger for this condition is often infection, mostly
bacterial and sometimes viral. Both ACS and COVID-19 pneumonia share a
similar clinical feature such as fever, cough, shortness of breath and
chest pain. Evidence from previous studies suggests that SARS-CoV2 could
trigger ACS[11]. Due to this overlap between ACS and pneumonia, it
is important to recognize the effect of COVID-19 in SCD patients[7].
Generally, patients with chronic comorbidities like diabetes,
hypertension, lung diseases and cardiovascular diseases are at increased
risk of COVID-19 complications. Noticeably, patients suffering from SCD
have a lot of complications as mentioned before. In the presence of this
multi-organ dysfunction,COVID-19 infection may trigger ACS or
VOC[12]. Also, the abnormality in endothelial and procoagulants
increase the risk of thromboembolic events, thus providing prophylactic
anticoagulants is essential [2].
A recent retrospective study conducted in Bahrain reviewed 387 patients
with SCD screened for COVID-19 infection, 6 patients had COVID-19
infection, all patients had favorable outcome, 3 patients were
asymptomatic and 3 had mild to moderate symptoms. The study concluded
that there is no difference among patients with SCD and non-SCD patients
in term of COVID-19 clinical course, viral clearance, and infection
rate. Also, no remarkable increased risk for SCD crisis[9]. In
contrast to our case where the patient had asymptomatic presentation
then developed acute painful episode with severe hemolysis. A case
series of 10 patients with SCD infected with COVID-19 in UK also showed
a good prognosis as 9 out of 10 patients recovered fully. Interestingly,
7 patients received blood transfusion (4 RBCs exchange and 3 simple
transfusion). It is worthy to notice that one patients in this series
died and she didn’t receive blood transfusion as she had delayed
hemolytic transfusion reaction as contraindication[13]. Another case
series for 4 patients with SCD and COVID-19 infection showed that all
patient presented with VOCs and had mild course, only one patient
deteriorated and needed Intensive Care Unit (ICU) admission where the
patient received RBCs exchange and improved remarkably. This case series
suggest good prognosis of COVID-19 infection and emphasize on the
importance of early RBCs exchange. However, none of the four patients
mentioned in this case had acute hemolytic anemia[3]. Nino
Balanchivadze et al published one center study that retrospectively
reviewed 24 patients with SCD anemia or trait infected with COVID-19, 4
patients had SCD, none of the included patients was taking hydroxyurea
(HU) the author concluded that patients with SCD generally had
unremarkable course of disease, low possibility of ICU admission and
intubation but hospitalization period might be longer [6]. It has
been hypothised that COVID-19 infection in patients with SCD precipitate
hemolysis because it affects hemoglobin beta chain, whereas others
suggested that patients with Thalassemia and SCD have immunity against
COVID-19 infection due to the defect in hemoglobin beta chain
[9][14][15]. The physiology behind this hypothesis as
published in one paper is that viral proteins like ORF1ab, ORF10 and
ORF3a might cause porphyrin-associated iron molecule in heme to
separate, this complex is located in the beta 1 chain, resulting in less
amount of Oxygen being carried by the hemoglobin in the blood
stream[15]. Patients with SCD as mentioned have mutation in beta
chain hemoglobin, whether this plays a role in the protection against
COVID-19 infection or not is still an area of research.
Red blood cells exchange is one way to treat severe ACS, a pervious data
suggested its use in the case of severe COVID-19 pneumonia overlapping
with ACS in patients with SCD. Moreover, it was noticed that whenever
RBCs exchange offered earlier, the prognosis and clinic course were
better[7][3]. In our case the patient improved after the red
blood cells exchange and we suggest that it might play a role in the
prevention of painful episode and hemolysis crisis progression if
offered earlier in the course of infection.
While RBCs exchange form an important component in the acute management
plan of SCD crisis, hydroxyurea is the mainstone in the maintenance
therapy. However, it is not recognized yet if compliance with this
therapy affects the presentation of COVID-19, data in this regard are
conflicting, one retrospective study screened 40 patients with SCD for
coronavirus infection, only 24 were positive and all of them were not on
HU, thus the authors suggested that HU in treatment might have a
protective effect against the virus. This was not the case in our
patients as he was on long term HU treatment and still had moderate
course of illness[6].
Admission of Patients with SCD and COVID-19 infection is essential even
if they are asymptomatic as they can develop acute painful episodes and
hemolytic crisis later in the course of infection like our reported
case. Although no final guideline is available now for the treatment of
SCD patients with COVID-19 infection, we believe that offering RBCs
exchange is an essential part of managing those population and we
recommend to offer it as earlier as possible to avoid deterioration.
Finally, the role of HU in the clinical course of coronavirus infection
is still not defined and form an area for further research.