|Year : 2022 | Volume
| Issue : 3 | Page : 199-203
Coronavirus disease 2019 in patients with sickle cell disease: A cross-sectional study from Jazan Province, Saudi Arabia
Abdulaziz Alhazmi, Wesam Ali Moafa, Jalal Madkhali, Othman Saifain, Faizah Alyahyawi, Ons Adhabi, Ahmad Ali Alharbi
Faculty of Medicine, Jazan university, Jazan 45142, Saudi Arabia
|Date of Submission||02-May-2021|
|Date of Decision||23-Mar-2022|
|Date of Acceptance||18-Apr-2022|
|Date of Web Publication||08-Jul-2022|
Microbiology and Parasitlogy department, Faculty of Medicine, Jazan university, Al Maarefah Rd, Jazan 45142
Source of Support: None, Conflict of Interest: None
Objectives: To assess the prevalence of coronavirus disease 2019 (COVID-19) infection among sickle cell disease (SCD) patients in Jazan region and to determine the impact of COVID-19 on the SCD population. Methods: This was an observational, descriptive, cross-sectional study using a self-administrated questionnaire directed to SCD patients in Jazan to assess the prevalence of COVID-19. The data were analyzed using a t-test and Chi-square test. Results: A total of 188 responses were received and only 96 SCD patients were included (mean age is 24 years). About half of the study samples (53%) of the study population were male. About 11% of patients with SCD were diagnosed with COVID-19. Vaso-occlusive crisis was reported in 73% and a single patient presented with acute chest syndrome. About three-fourths of patients (73%) were admitted to the hospital and most of them experienced mild symptoms and one patient was treated in the intensive care unit. Conclusion: SCD patients are at risk of SARS-CoV-2 infection. In the absence of comorbidities, patients with SCD are not at increased risk of COVID-19 mortality, but a higher admission rate is reported. SCD patients with COVID-19 may have a milder clinical course, compared to other populations with comorbidities such as diabetes and hypertension, and this may be due to proinflammatory adaptation of the immune system. Larger studies including epidemiological and molecular details are needed to enhance our understanding of how SARS-CoV-2 could affect patients with SCD.
Keywords: Coronavirus disease 2019, Jazan, SARS-CoV-2, Saudi Arabia, sickle cell disease
|How to cite this article:|
Alhazmi A, Moafa WA, Madkhali J, Saifain O, Alyahyawi F, Adhabi O, Alharbi AA. Coronavirus disease 2019 in patients with sickle cell disease: A cross-sectional study from Jazan Province, Saudi Arabia. J Nat Sci Med 2022;5:199-203
|How to cite this URL:|
Alhazmi A, Moafa WA, Madkhali J, Saifain O, Alyahyawi F, Adhabi O, Alharbi AA. Coronavirus disease 2019 in patients with sickle cell disease: A cross-sectional study from Jazan Province, Saudi Arabia. J Nat Sci Med [serial online] 2022 [cited 2022 Aug 17];5:199-203. Available from: https://www.jnsmonline.org/text.asp?2022/5/3/199/350302
| Introduction|| |
Sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy. It occurs due to a mutation in the hemoglobin-beta gene found on chromosome 11, and it results in an abnormal crescent shape of red blood cell (RBC). These abnormal RBCs can occlude small blood capillaries causing hypoxic injury, ischemia, and tissue damage, which lead to body organ complications such as acute chest syndrome (ACS,) vaso-occlusive crisis (VOC), stroke, and other complication. SCD is composed of many subtypes of hemoglobinopathies. The most common type is HbSS or sickle cell anemia, which affects about 300,000 children worldwide. Saudi Arabia is considered one of the countries that recorded a higher prevalence of SCD, in which 5 per 1000 children and about 0.38 per 1000 children reported to have sickle cell trait and SCD, respectively. Jazan, which is a southwestern region of Saudi Arabia, reported having a high prevalence rate of SCD, which is about 7% of the total population. The diagnosis of SCD is established by hemoglobin electrophoresis and a positive sickling test result and managed with regular follow-up, hydroxyurea, blood transfusion, and considerable referral for hematopoietic stem cell transplantation.
The present outbreak of coronavirus disease 2019 (COVID-19) is caused by a newly identified strain of positive-strand RNA coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As per the end of April 2021, COVID-19 has affected about 128 million people and total death cases are reaching over 2.8 million worldwide. In Saudi Arabia, over 390 thousand cases were diagnosed with COVID-19, with a total of 6676 death cases being reported as per the World Health Organization (WHO).
SCD patients are considered a risk group when they are diagnosed with COVID-19, and SARS-CoV-2 has been suggested to be a triggering factor of sickle cell crisis.,, The impact of COVID-19 on SCD has not been identified and still needs to be elucidated. However, during the COVID-19 pandemic, the Saudi Ministry of Health has identified SCD patients as a high-risk group. In contrast, several reports have shown favorable outcomes of COVID-19 on SCD population.,,, Thus, in this study, we aimed to estimate the prevalence of COVID-19 infection among SCD patients in the Jazan region and to determine the impact of COVID-19 on the SCD population.
| Methods|| |
A descriptive, cross-sectional web-based study was conducted between December 15, 2020, and February 15, 2021, targeting patients with SCD in Jazan region of Saudi Arabia. Population included all patients diagnosed with SCD in Jazan. However, non-SCD participants, patients with SCD outside the Jazan region, and patients who did not complete the survey were excluded. The data were collected as an anonymous self-administered questionnaire. Quantitative variables were selected based on the study's primary goals. Study variables included age, sex, further details on SCD complications, admission rate to ward or intensive care unit (ICU), and blood transfusion. We used descriptive closed-ended questions to explore the relationship between SCD and multiple variables, and to reduce the risk of confounding, we used closed-ended questions of SCD patients and COVID-19 risk exposure. Choosing answers to our questionnaire is obligatory and must be completed to be submitted, a way that can eliminate the risk of missing data. The collected data were verified manually and then entered into a personal computer and were analyzed using the Statistical Package for the Social Sciences SPSS v.23 (IBM Corp., Armonk, NY, USA). The data were analyzed using t-test and Chi-square test. P < 0.05 was considered statistically significant.
| Results|| |
A total of 188 responses were received and only 96 SCD patients met our inclusion criteria. The median age of participants was 24 years with a range of 4–44 years. The majority of the study patients were male (n = 51, 53.1%). The general characteristics of the patients are summarized in [Table 1]. Eleven (11%) patients were diagnosed with COVID-19 [Table 2]. Among those patients, 8 (73%) patients reported VOC symptoms during COVID-19, and two patients were diagnosed with ACS and chest infection. Most of the cases experienced mild symptoms except two cases reported symptoms of chest infection. About 73% of the patients were admitted to hospitals and only one patient was treated in ICU. About half of the admitted patients required oxygen treatment. Four patients have received blood transfusion and an exchange transfusion was performed for one patient with ACS. Oxygen treatment was given for six patients. The data showed three patients with other comorbidities including kidney diseases, asthma, and thyroid diseases; all the patients infected with SARS-CoV-2 were recovered. [Table 3] shows patients with SCD who presented with COVID-19 against SCD patients without COVID-19.
|Table 2: General characteristics of sickle cell disease patients with coronavirus disease 2019 (n=11)|
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|Table 3: Comparison of sickle cell disease patients with coronavirus disease 2019|
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| Discussion|| |
Since the WHO has announced COVID-19 as a pandemic on March 11, 2020, different vulnerable groups were identified as high-risk groups due to the increased risk of morbidity and mortality among these groups. Patients with SCD were classified as a risk group by different health officials, such as the Ministry of Health in Saudi Arabia. Jazan province, in the southwestern region of Saudi Arabia, is considered to be one of the highest prevalent provinces for SCD in the country. Alsaeed et al. found that the prevalence of SCD in Jazan is about 7%, in which VOC and ACS were the major causes for hospital admission with 56% and 12% respectively. In our study, 86% of SCD patients had at least one admission rate per year and this admission rate is in line with different studies.,
To evaluate whether SCD patients are at risk for SARS-CoV-2 infection, we found that 11% of our study group were diagnosed with COVID-19. The majority of the cases were mild with favorable outcomes. About 73% of the COVID-19 patients reported VOC symptoms, a finding that suggests that the possibility of SARS-CoV-2 could trigger a sickling crisis even without initiation of COVID-19 respiratory manifestations., Our study reported mild clinical course in 82% of SCD patients diagnosed with COVID-19, while the respiratory symptoms were reported only in two patients.
Abdulrahman et al. compared the risk of COVID-19 in the SCD group versus the non-SCD group and had shown no difference in the infection rate, clinical course, and viral clearance between the two groups. However, SCD patients with preexisting cardiopulmonary diseases, kidney diseases, and/or stroke and not receiving hydroxyurea may be at higher risk for death from COVID-19. The admission rate of the SCD population with COVID-19 in our study (72%) was consistent with Panepinto et al.'s study, in which the admission rate was 70%. The high admission rate in the SCD group could be explained by the cautious attitude of the treating physicians toward this group due to known SCD complications. However, no significant difference was found between SCD and non-SCD patients in ICU admission and this may be due to the small sample size included in our study. McCloskey et al. studied the importance of COVID-19 testing in SCD patients who presented only with VOC events, even if those patients do not report a history of contact with COVID-19 cases or manifest symptoms of SARS-CoV-2 infection. Thus, clinicians are encouraged to consider such a presentation when they deal with SCD patients. Besides, viral infection can trigger acute VOC and ACS in SCD, and these complications are associated with high mortality rates.
Of note, our data are limited by the absence of deceased individuals with SCD who are infected with SARS-CoV-2, due to the cross-sectional nature of the study; however, Sayad et al. sought the association between COVID-19 mortality in patients with SCD. Three out of 13 studies reported COVID-19-related death in patients with SCD. It is noteworthy that Sayad et al. reviewed articles of 459 patients with SCD who are infected with SARS-CoV-2, and only three patients (<1%) died due to the consequences of COVID-19 and SCD. Further, about 42% (191) of patients with SCD were admitted to hospital, of whom 7% (32) were admitted to ICU. Taken together, mortality rate of patients with SCD who are infected with SARS-CoV-2 is not increased, and this might be due to the current treatment for patients with SCD that may include good hydration, analgesia, frequent blood transfusion, and hydroxyurea, and these treatments could contribute to the mild form of SCD during COVID-19 infection. More studies are needed to confirm this finding, especially among the SCD population with established comorbidities such as kidney and thyroid diseases. Moreover, it is known that the preexisting state of the proinflammatory and procoagulant status in SCD patients with COVID-19 may play role in the milder clinical symptoms our patients experience during COVID-19.,,, High circulating levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) have been reported in SCD patients at steady or nondiseased state. Similar inflammatory markers were reported to be directly upregulated in the case of SARS-CoV-2 infection. Another possible mechanism is that the baseline increased TNF and IL-6 may make innate immune cells less responsive, as it has been reported for type 1 interferons in COVID-19 responses., Consequently, SCD background of chronic inflammation, and hemolytic status, in the absence of preexisting cardiopulmonary or kidney diseases, might have ultimately improved adaptation of the immune response of SCD patients to COVID-19, and further researches are warranted to elucidate this relationship and its exact role in SCD patients who are infected with SARS-CoV2. On other hand, a few articles reported observations that differ from those in our study., For example, Boğa et al. conducted a recent study on 39 SCD patients compared to 121 subjects in the control group. It was found that 9% of SCD patients who diagnosed with COVID-19, compared to 23% of the control group. The clinical picture of SCD patients with COVID-19 was worse, in which this group presented with significantly more fever, loss of taste and smell, and pneumonia and abnormalities in chest X-ray and computed tomography. Moreover, the abnormalities in the laboratory findings of SCD patients were significantly more prominent, compared to the control group. They concluded that the clinical course of COVID-19 in SCD patients could be worse. Thus, a national study that includes a larger population is warranted for a better conclusion for the relationship between COVID-19 and SCD.
Limitation and strength
Our study has many limitations. Although it is an online questionnaire directed to SCD patients in Jazan province, this kind of online observational study has its known bias, especially when it has a low number of participants with SCD who had COVID-19, and failed to include participants with SCD who may be presented with severe cases or died due to COVID-19. Further, we have no molecular tests for COVID-19-positive patients. The low response rate of SCD patients with COVID-19 and possible limited access to the survey during the pandemic should be considered. Moreover, the questionnaire failed to include questions such as the use of hydroxyurea or anticoagulation during their hospitalization and their effects on SCD patients with COVID-19. However, we believe that we included real regional data of SCD patients in the Jazan region, in addition to patients' viewpoints of their disease condition. Moreover, to our knowledge, this is the first study during the COVID-19 pandemic to explore the SCD population with or without COVID-19 in Jazan.
| Conclusion|| |
SCD population are at risk of acquiring COVID-19 and they need to be closely monitored and evaluated regardless of the presenting symptoms. Patients with SCD who are diagnosed with COVID-19 seem not to bear an increased risk of morbidity or mortality of COVID-19, but a higher hospitalization rate is reported. SCD patients, without predisposing comorbidities, who present with the COVID-19 may not have poor outcome and this may be due to chronic background inflammation and immunomodulatory adaptation and upregulation. Thus, further epidemiological and molecular studies on a larger population are needed to assure a better understanding of the effects of SARS-CoV-2 infections on SCD patients.
Ethical approval was granted by Jazan University (# REC42/1/070) dated December 14, 2020, and informed consent was obtained from all participants.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Baltierra D, Harper T, Jones MP, Nau KC. Hematologic disorders: Sickle cell disease. FP Essent 2015;433:27-39.
Piel FB, Steinberg MH, Rees DC. Sickle cell disease. N Engl J Med 2017;377:305.
Hazzazi A, Ageeli M, Alfaqih A, Jaafari A, Malhan H, Bakkar M. Epidemiology and characteristics of sickle cell patients admitted to hospitals in Jazan region, Saudi Arabia. J Appl Hematol 2020;11:10. [Full text]
Alsaeed ES, Farhat GN, Assiri AM, Memish Z, Ahmed EM, Saeedi MY, et al.
Distribution of hemoglobinopathy disorders in Saudi Arabia based on data from the premarital screening and genetic counseling program, 2011-2015. J Epidemiol Glob Health 2018;7 Suppl 1:S41-7.
AbdulRahman A, AlAli S, Yaghi O, Shabaan M, Otoom S, Atkin SL, et al.
COVID-19 and sickle cell disease in Bahrain. Int J Infect Dis 2020;101:14-6.
Ganesh B, Rajakumar T, Malathi M, Manikandan N, Nagaraj J, Santhakumar A, et al.
Epidemiology and pathobiology of SARS-CoV-2 (COVID-19) in comparison with SARS, MERS: An updated overview of current knowledge and future perspectives. Clin Epidemiol Glob Health 2021;10:100694.
Arlet JB, de Luna G, Khimoud D, Odièvre 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.
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;26:2473-6.
Sahu KK, Siddiqui AD, Cerny J. Managing sickle cell patients with COVID-19 infection: The need to pool our collective experience. Br J Haematol 2020;190:e86-9.
Menapace LA, Thein SL. COVID-19 and sickle cell disease. Haematologica 2020;105:2501-4.
Minniti CP, Zaidi AU, Nouraie M, Manwani D, Crouch GD, Crouch AS, et al.
Clinical predictors of poor outcomes in patients with sickle cell disease and COVID-19 infection. Blood Adv 2021;5:207-15.
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.
Azerad MA, Bayoudh F, Weber T, Minon JM, Ketelslegers O, Hoyoux M, et al
. Sickle cell disease and COVID-19: Atypical presentations and favorable outcomes. EJHaem 2020;1:338-41.
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;1:384-7.
Sayad B, Karimi M, Rahimi Z. Sickle cell disease and COVID-19: Susceptibility and severity. Pediatr Blood Cancer 2021;68:e29075.
Conran N, Belcher JD. Inflammation in sickle cell disease. Clin Hemorheol Microcirc 2018;68:263-99.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al.
COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4.
Madany E, Lee J, Halprin C, Seo J, Baca N, Majlessipour F, et al.
Altered type 1 interferon responses in alloimmunized and nonalloimmunized patients with sickle cell disease. EJHaem 2021;2:700-10.
Madany E, Okwan-Duodu D, Balbuena-Merle R, Hendrickson JE, Gibb DR. Potential implications of a type 1 interferon gene signature on COVID-19 severity and chronic inflammation in sickle cell disease. Front Med (Lausanne) 2021;8:679030.
Boğa C, Asma S, Leblebisatan G, Şen N, Tombak A, Demiroğlu YZ, et al.
Comparison of the clinical course of COVID-19 infection in sickle cell disease patients with healthcare professionals. Ann Hematol 2021;100:2195-202.
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.
Singh A, Brandow AM, Panepinto JA. COVID-19 in individuals with sickle cell disease/trait compared with other black individuals. Blood Adv 2021;5:1915-21.
[Table 1], [Table 2], [Table 3]