COVID-19 in patients with sickle cell disease: A single center experience from Ohio, United States.

Dear Editor,

Coronavirus disease 2019 (COVID‐19) pandemic is expanding at an enormous pace and has already affected over 15 million population. Individuals with comorbidities are the worst affected with risk factors like old age, diabetes, chronic airway disease, immunosuppressed, and cancer. Sickle cell disease (SCD) is a common genetic disease and needs special care owing to impaired immunity and compromised cardiopulmonary system. Hereby, we share our institutional experience with SCD patients during the COVID‐19 pandemic

In our chart review (approved from the institutional review board), we captured five laboratory‐confirmed COVID‐19 patients with SCD. Four patients required inpatient treatment, while the other one was managed as an outpatient. The average age of the patients was 32. 6 years (range 21–47 years) with three females and two males. Only two out of five were on chronic therapy with hydroxyurea. Importantly, two out of the five patients presented to us only with generalized body aches. Three patients had classical imaging findings suggestive of COVID‐19 disease. None of the patients required intensive care or mechanical ventilation with only one patient had a new oxygen requirement (Table 1). Only one patient (Patient no. 1) required transfusion support for symptomatic anemia. The same patient did receive remdesivir therapy for COVID‐19 pneumonia. All patients except one (Patient no. 5) received prophylactic anticoagulation as per institutional policy with 1 mg/kg enoxaparin once daily. Patient no. 5 was never hospitalized and hence did not require any anticoagulation. None of the patients develop any thrombotic complications like deep venous thrombosis or pulmonary embolism. During the hospital stay, none of the patients developed lymphopenia, thrombocytopenia, coagulopathy. There was 100% recovery with an average hospital stay of 8.75 days (Table 2).

Table 1

Demographic details, genotype, COVID‐19 symptomatology, and management

SN	Age/sex	Genotype	Comorbidities	On treatment if any	Symptoms	RT‐PCR	Imaging findings	Maximum oxygen requirement	ICU stay/mechanical ventilation	RBC exchange therapy	Simple transfusion	Treatment given for COVID	hospital stay (in days)	Outcome
1	38/M	SS	Iron overload	Hydroxyurea, dDeferasirox	Cough, malaise, abdominal pain, nausea, vomiting, anorexia X 3 days	Positive	Bilateral pulmonary congestion, multifocal opacities	3 L (via Nasal Cannula)	Not required	Not required	Yes, 4 units PRBCs	Remdesivir	6	Discharged
2	28/F	SC	Obesity (BMI 54)	None	Pain, Shortness of breath, dyspnea on exertion X 5 days	Positive	Right lower lobe opacity	Not required	Not required	Not required	Not required	Not required	15a	Discharged
3	47/F	S B‐thal	Asthma	None	Body pain X 2 days	Positive	Patchy bibasilar infiltrates	2 L at night (chronic, home O2)	Not required	Not required	Not required	Not required	11	Discharged
4	29/M	SS	Hypertension	Hydroxyurea	Body pain X 3 days	Positive	Normal	1 L at night (chronic, home O2)	Not required	Not required	Not required	Not required	3	Discharged
5	21/F	SC	Anoxic brain injury, seizures	None	None	Positive	Not done	Not required	Not required	Not required	Not required	Not required	0b	Improved

Abbreviations: BMI, body mass index; COVID‐19, coronavirus disease 2019; ICU, intensive care unit; RT‐PCR, reverse transcription‐polymerase chain reaction.

Patient no. 2 got readmitted within 24 h of discharge after initial 5 days of hospitalization due to dyspnea on exertion. Second hospitalization was for 10 days (total duration of hospitalization was 15 days).

Patient no. 5 never required admission and was managed as an outpatient.

Table 2

Laboratory parameters of patients

SN	Nadir Hb	Nadir reticulocyte count	Nadir ALC	WBC count	Nadir Platelet count	Zenith d ‐dimer	Zenith CRP	Zenith Ferritin	Zenith LDH	Zenith PT	Zenith APTT	Zenith AST	Zenith ALT	Zenith Total/Direct Bilirubin	Zenith S. creatinine
1	6.8	0.092	2.45	6.4	263	4283	4.8	3840	617	14.5	29	58	42	2.7/0.6	0.86
2	8.8	0.077	1.87	9.5	534	1197	4.63	131	471	13.2	22	38	42	1.8/0.4	0.72
3	8.2	0.262	1.92	8.5	368	21567	6.96	187	409	13.8	68	30	12	0.9/0.2	0.52
4	9.2	0.516	2.96	8.3	310	3918	0.39	425	561	11.4	27	65	38	2.7/0.5	0.87
5	Not done	Not done	Not done	Not done	Not done	Not done	Not done	Not done	Not done	Not done	Not done	Not done	Not done	Not done	Not done

Note: Reference range: Hb, 13.5–17.5 g/dl; reticulocyte count, 0.022−0.118 × 1012/L; ALC, 1.2−4.8 × 109/L; WBC count, 4.4−11.3 × 109/L; platelet count, 150 × 450 × 109/L; ‐dimer, <500 ng/ml; CRP, <1.0 mg/dl; ferritin, 20–300 mcg/L; LDH, 84–246 U/L; PT, 9.7–12.7 s; APTT, 25–36 s; AST, 9–39 IU/L; ALT, 10–52 IU/L; T/C Bil. Total, 0.0–1.2 mg/dl, and direct, 0.0–0.3 mg/dl; S. creatinine, 0.5–1.3 mg/dl.

Abbreviations: ALC, absolute lymphocyte count; APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; ALT, alanine aminotransferase; CRP, C‐reactive protein; Hb, hemoglobin; LDH, lactate dehydrogenase; PT, prothrombin time; WBC, white blood cells.

The severe acute respiratory syndrome coronavirus 2 virus can act as a potential trigger to acute chest syndrome (ACS) in SCD patients. Factors, such as hypersplenism, vasculopathy, iron overload, and recurrent veno‐occlusive crisis (VOCs) leads to impaired immunity that can lead to more fatal outcome than non‐SCD patients in COVID‐19 pneumonia. Also, to note that the clinical presentations of COVID‐19 related ACS, COVID‐19 pneumonia, and bacterial pneumonia can overlap (Figure 1). This could be challenging especially in a scenario when one or more entities co‐exist in a same patient. In general, diffuse ground glass appearance in imaging is more commonly seen in COVID‐19 pneumonia than ACS or bacterial pneumonia. Other classical findings like hemolysis, rapid falling hemoglobin, bone aches could be more suggestive of ACS than COVID‐19 per se. However, in practical scenario it might be extremely difficult to definitively rule out one possibility over the other.

Figure 1

Three common differentials for respiratory complaints in a patient with SCD during COVID‐19 pandemic. COVID‐19, coronavirus disease 2019; SCD, sickle cell disease

SECURE‐SCD global registry, an initiative by The Medical College of Wisconsin is an excellent platform to collaborate the cases of SCD acquiring COVID‐19 and their outcome (https://covidsicklecell.org/updates-data/). The latest data (updated till July 17, 2020) shows 260 cases of SCD registered from across the world (mostly from the US) with an average age of 26.83 years, and African American females being the worst affected population. Just like our patient series, the majority of the patients from the registry were on hydroxyurea and without any chronic transfusion therapy. An interesting observation which we also noted in our case series that, 31.15% of patients (81 out of 260) presented with symptoms of pain only. The majority of the patients (54.62%) had mild symptoms with a mortality rate of 6.15%. The second‐largest study reported includes a French experience with 83 SCD patients with COVID‐19 (multicentric study, 24 hospitals). The French group showed that the prevalence of intensive care admission was more with advanced age (53% in the older group, the median age of 54 years vs. 13% in the younger group, the median age of 28 years). The majority of the patients have associated VOCs (54%, 44 out of 81 patients), followed by ACS (28%, 23 out of 82 patients). 20% of the patients required ICU care which is almost like the results reported by SECURE‐SCD global registry (25% were severe or critically ill). In addition to the above‐mentioned studies, the other two largest single‐center studies reported till now, both from the UK included 10 patients each. ,

In conclusion, treating COVID‐19 in SCD patients' needs a multidisciplinary approach with the management of pneumonia, VOCs, ACS, and supportive care at the same time for the best outcome.

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.

AUTHOR CONTRIBUTIONS

All the authors played a significant role (manuscript writing, data collection, literature search, reviewing the paper, editing, and proofread) in the paper.