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ORIGINAL ARTICLE
Year : 2023 | Volume
: 67
| Issue : 1 | Page : 112-116
Impact of COVID-19 infection among indian sickle cell disease patients
Naveen Khargekar1, Nikhil Shinde2, Anindita Banerjee1, Manisha Madkaikar3, Anita Nadkarni4
1 Scientist E, Department of Transfusion Transmitted Diseases, ICMR-NIIH, Mumbai, Maharashtra, India
2 Senior Research Fellow, ICMR-Center for Research, Management and Control of Haemoglobinopathies, Chandrapur, Maharashtra, India
3 Scientist G, Department of Paediatric Immunology and Leukocyte Biology, ICMR-NIIH, Mumbai, Maharashtra, India
4 Scientist F, Department of Haematogenetics, ICMR-NIIH, Mumbai, Maharashtra, India
Correspondence Address:
Naveen Khargekar
Department of Haematogenetics, ICMR-National Institute of Immunohaematology, 13th Floor, New Multistoreyed Building, KEM Hospital Campus, Mumbai - 400 012, Maharashtra
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/ijph.ijph_1230_22
Abstract
Background: Sickle cell disease (SCD) is one of the most common hemoglobinopathy disorders and is widely prevalent in India, especially in the tribal population. SCD patients are prone to develop recurrent respiratory infections and related complications owing to the microvascular occlusion and impaired immunological response. Objectives: We aimed to determine the prevalence and impact of COVID-19 in SCD patients from India. Methodology: We conducted a cross-sectional study in Chandrapur district of Maharashtra, India, between August and October 2021. After taking informed consent, details of 300 SCD patients' demographic data, history of COVID-19 testing, infection, symptoms related to COVID-19 in the past 1 year, hospitalization, complications, mortality, COVID-19 vaccination, and side effects were recorded. Results: We found that 93 (31%) of SCD patients had influenza-like symptoms during the COVID-19 pandemic with symptoms of fever (81.72%), cough (35.48%), sore throat (18.27%), headache (15.05%), and breathlessness (7.52%). A total of 13 (4.33%) SCD among 300 SCD were tested as COVID positive. Majority of them were mild cases and the 1st dose of COVID-19 vaccine was received by 47 (29.37%) of SCD patients and 10 (6.02%) of the patient had received second dose of vaccine. Conclusion: Low incidence of COVID-19 and milder disease spectrum in our study cohort suggests that there is no increased risk of COVID-19 mortality and morbidity in SCD patients compared to general population. However, the reason for low COVID vaccination in our study could be due to the fear of complications of COVID vaccine.
Keywords: COVID-19, mortality, severity, sickle cell disease
Introduction 
Sickle cell disease (SCD) is one of the most common hemoglobinopathy disorders affecting millions of children globally.[1] The burden of SCD is high in malaria-endemic regions of sub-Saharan Africa, Mediterranean basin, Middle East, and India.[2],[3] In India, the prevalence of SCD is high among the tribal population, who account for 8.6% of the total population.[4]
SCD is an autosomal recessive single gene disorder characterized by the production of an abnormal hemoglobin (Hb), Hb S (HBB:c.20A>T), due to point mutation at codon 6 of the β-globin gene located on chromosome 11. This abnormal hemoglobin (HbS) under hypoxic conditions becomes poorly soluble, which leads to polymerization of HbS molecules making it insoluble and rigid. This leads to microvascular obstruction and ischemic reperfusion injury in the microvasculature leading to pain and organ damage.[5]
In SCD patients nearly all organs are affects leading to multiorgan damage making them more susceptible to infection and early mortality.[6],[7] The study done on the US population showed that the life expectancy is almost 25 years lower in SCD patients compared to the general population.[8] Due to repeated pulmonary infection in SCD patient, there is an alteration of elastic and collagen fibers and the lung parenchyma resulting in ventilation-perfusion imbalance and decreased pulmonary capacity leading to both obstructive and restrictive patterns of decreased pulmonary function. The severity of respiratory infection and duration of hospital stay is higher in SCD patients compared to non-SCD patients.[5]
The emergence of the COVID-19 pandemic in the year 2020 caused by severe acute respiratory syndrome coronavirus 2 has affected people globally with a sizeable number of mortality and morbidity. The clinical features of COVID-19 infection vary from being asymptomatic to mild flu-like illness to severe respiratory distress. The risk of severe respiratory distress and death in COVID-19 infection are higher in people having preexisting morbidities which also includes organ dysfunction seen in SCD patients.[9] Therefore, SCD persons are likely to be more vulnerable to increased risk of morbidity and mortality due to COVID-19.
Literature suggests that SCD patients are more susceptible to infection due to impaired leukocyte function and decreased humoral and cell-mediated immunity.[10] These patients also have pulmonary complications such as pulmonary hypertension and acute chest syndrome and infection with COVID-19 increases the risk for developing fatal complications and mortality.[11] The COVID-19 virus acts through angiotensin-converting enzyme 2, CD147, and CD26 of red blood cells causing dysfunctional Hb leading to reduced heme oxygen carrying capacity.[12] These can also incite vaso-occlusive coagulopathy, increased vascular permeability, and fluid accumulation in the lung leading to life-threatening complications.
It was thought that COVID-19 could be devastating in the regions having high prevalence of SCD mainly in Africa and India, where an estimated 8–12 million patients with SCD live. However, there are limited data on the effect of COVID-19 infection among SCD patients globally and no studies in the Indian population. Therefore, we conducted a cross-sectional study in a cohort of SCD patients in India to assess the morbidity and mortality pattern during COVID-19 pandemic.
Methodology This was a cross-sectional study conducted in Chandrapur district of Maharashtra, India. The Indian Council of Medical Research-National Institute of Immunohaematology is monitoring the SCD patients of Chandrapur district for periodic screening and treatment for organ damage. Ethical approval was obtained from Institutional Ethics Committee at Government Medical College, Chandrapur (dated June 3, 2020) before the start of the study.
This survey was conducted from August 1, 2021, to October 15, 2021. Using a semi-structured questionnaire, a trained interviewer after telephonic consent contacted 370 SCD patients of our SCD cohort. Of these 370 SCD patients, 300 consented and agreed to participate in the study. The data regarding the demographic details, history of COVID-19 testing, COVID-19 infection, symptoms related to COVID-19 in the past 1 year, hospitalization details, COVID-19 vaccination, and its any side effects were recorded. The severity of COVID-19 infection was classified as asymptomatic, if the tested positive patient did not have any symptoms, as mild if the patient had symptoms of COVID-19 without any respiratory distress and was in home quarantine and moderate/severe in case of hospitalization, and SPo2 less than 94%. We randomly tested few non-vaccinated SCD patients using an ImmunoQuick COVID-19 test which detects immunoglobulin M and immunoglobulin G Antibodies to the COVID-19 virus in human serum.
Results We collected information from 300 SCD patients of our SCD cohort. Of these 300 SCD patients, 166 (55.33%) patients were males and 134 (44.66%) were females. One hundred and thirty-four (44.67%) were above the age of 20 years [Table 1]. All 300 SCD patients had a confirmed molecular diagnosis report of sickle cell anemia.
During the survey, we found that the family members of 35 (11.67%) SCD patients were tested positive for COVID-19. Among these 23 (65.71%) SCD patients were in direct contact with the COVID-19-positive patients without wearing mask and in close contact for more than 15 min duration. Twenty-nine SCD patients had high-risk contact with laboratory-confirmed COVID-19-positive patient, of which 23 (79.31%) SCD patient had contact at home and 6 (20.68%) had contact at workplace. Of these 29 SCD who were at high-risk contact, only 22 (75.8%) tested for COVID with reverse transcription polymerase chain reaction (RT-PCR) or rapid antigen test (RAT), among this 7 (31.8%) tested positive. All the adult SCD patients and parents of pediatric patients were aware of the risk of COVID-19 transmission and considered SCD as high risk and took precautions to prevent COVID-19 transmission.
Of the 93 (31%) of SCD patients had influenza-like symptoms during the COVID-19 pandemic. Fever was the most common symptom in 76 (81.72%) patients followed by cough in 33 (35.48%) patients, sore throat in 17 (18.27%) patients, and headache in 14 (15.05%) patients and breathlessness in 7 (7.52%) patients [Figure 1]. Of the 93 (31%)) SCD patients who had influenza-like symptoms, 34 (36.55%) got themselves tested for COVID-19 by RT-PCR or RAT. The test positivity rate among symptomatic was found to be 23.52% whereas the test positivity rate among asymptomatic was 10.41%. Total of 13 (4.33%) SCD among 300 SCD were tested as COVID-19 positive. Of the 15 nonvaccinated SCD patients tested for COVID-19 antibody, 7 (46.66%) were previously infected with COVID-19 infection.
Of the total 13 tested positive for COVID-19 infection, most of them 9 (69.23%) were above 18 years of age. Five (38.46%) were asymptomatic, 7 (53.84%) had mild infection and had taken treatment at home and only one case of SCD had severe COVID infection leading to hospitalization [Table 2]. More than 90% of COVID-infected SCD recovered completely without any complications like vaso-occlusive crises.
Table 2: Severity of coronavirus disease-2019 positive cases detected by reverse transcriptase-polymerase chain reaction/rapid antigen testThe clinical details of one patient who had a severe infection are as follows. He was a 30 years male patient in home isolation initially for 2 days with a fever with cough, following which he developed breathlessness and hypoxia (SpO2 below 90%). He required hospitalization for oxygen support. However, there was no history of blood transfusion. No data were available on organ damage. The computed tomography chest severity score was 11/25 with extensive ground glass opacities involving upper, middle, and lower lobes. Serum markers were elevated with lactate dehydrogenase-931.5U/L, Ferritin-375ug/L, and D dimer-3700 ng/ml. Complete blood count showed very high N:L ratio of 5.42 indicating severe lymphocytopenia which is pathognomonic of COVID-19. He succumbed to COVID-related complications after 5 days of hospitalization.
One hundred and sixty (53.33%) SCD patients in the surveyed cohort were above the age of 18 years and eligible for COVID-19 vaccination as per the national guidelines. Of these only 47 (29.37%) of SCD patients had received the first dose of COVID vaccine and 10 (6.02%) of SCD patient had received the second dose of the vaccine. Post-COVID-19 Vaccination in SCD patients, Fever was the most common adverse event seen in 9 (19.14%) of vaccinated sickle cell patient. None of the vaccinated SCD patients had precipitation of vasoocclusive crises after COVID-19 vaccination.
Discussion SCD patients are said to be immunocompromised and susceptible to frequent infection.[5],[13] The case positive rate in SCD cohort was 15.85% which was similar to total positive rate during the second wave of the COVID-19 pandemic in many parts of India.[14] This shows that SCD patients of India are not at increased risk to COVID-19 infection as thought earlier. Similar findings were found in a retrospective study conducted in Bahrain, where there was no increased risk of COVID-19 infection among SCD patients.[15]
Most of the SCD patients and their family members were aware of increased risk of COVID-19 infection among SCD individuals and were taking precautions for the prevention of the disease. Still 23 SCD patients were in high-risk contact for COVID-19 at home and 4 (11.42%) tested positive for COVID, which is similar to overall household transmission was 10.1% in the general population.[16]
As more than 90% of COVID-19 infection in India are asymptomatic, so many do not get tested for COVID-19 infection and go unnoticed.[17] On the contrary, even many symptomatic patients did not undergo test for COVID-19 infection due to the fear of stigmatization. In our SCD cohort, we had 93 symptomatic individuals out of which only 34 (36.55%) tested for COVID-19 infection with RTPCR or RAT. This shows that more than 50% of SCD patients symptomatic for COVID infection did not get themselves tested. This could be attributed to fear of stigmatization. Similar hesitance in opting for COVID-19 testing among symptomatic individuals was reported in parts of Maharashtra.[18]
With regard to symptoms, more than 90% of COVID-19-positive SCD patients were asymptomatic or in mildly symptomatic with fever, cough and sore throat were the most common symptoms which is in agreement with clinical course of COVID-19 infection in general population.[19]
It is said that infections may induce crises in SCD patients and reports suggested worse COVID-19 complications in these patients.[20],[21] Of the 13 who tested positive for COVID-19 infection in our study, more than 90% were asymptomatic or of mild impact and they recovered completely without any precipitation of vaso-occlusive crises. Similar findings were found in a study conducted in Chennai, where around 90% of the cases were asymptomatic or mildly symptomatic among the general population.[22] The above finding suggests a similar course of COVID-19 infection in SCD patients to that of the general population. In addition, COVID-19 infection in SCD patients did not lead to increased vaso-occlusive crises in our cohort. This can be explained by already elevated pro-inflammatory cytokine like interleukin (IL)-1, IL-6, and tumor necrosis factor-α are raised in SCD patients leading to lesser trigger of cytokine storm following COVID-19 infection in SCD patients as they are already accustomed to a Chronic inflammatory state. Similar observations were reported by Ramachandran et al. in the US population.[23]
As per the serosurveillance conducted in general population by the health department in October and November 2020, 36.5% were infected with COVID-19 in Chandrapur district.[24] Even among the 15 nonvaccinated SCD patients randomly tested for COVID-19 antibody, 46.66% were found to be positive for COVID-19 antibody. Hence, more than 130 SCD patients would have been infected with COVID-19 infection. However, the mortality of one SCD patient in the Cohort suggests that SCD patients are probably not at increased risk for mortality due to COVID-19 compared to mortality due to COVID-19 in general population.[25]
In our study, 53.33% of the SCD patients were above the age of 18 years and were eligible COVID-19 vaccination. However, only 29.37% and 6.25% of the eligible population had received first and second doses of COVID-19 vaccine, respectively. This is slightly low compared to the vaccination of the general population in that region, which was 34.52% of the eligible people in Vidarbha area were vaccinated with at least one dose till the end of July 2021.[26] The reason for low vaccination could be due to the fear of complications of COVID-19 vaccine in SCD patients. This vaccine hesitancy is common among general population also and with behavioral change communication campaign, this fear can be alleviated.[27]
Although an episode of severe vaso-occlusive crises in 3 SCD patients post-COVID-19 vaccination has been reported by one study,[28] however, none of the vaccinated SCD patient in our study cohort had a precipitation of vasoocclusive crises after COVID-19 vaccination. Fever was the only adverse event seen in postvaccination 9 (19.14%). Our data suggest that COVID-19 vaccination is safe in SCD patients in the Indian population and these patients should be motivated to get themselves vaccinated.
Our study has few limitations. First of all, data from the SCD patients were obtained through telephonic conversation which could lead to recall bias in terms of underreporting or overreporting of certain information. However, due to COVID-19 restrictions, it was only a feasible way to gather data from SCD patients. Second, because of the asymptomatic nature of COVID-19 infection and unavailability of COVID-19 testing/diagnosis for all SCD patients, the actual prevalence might have been much higher. Nonetheless, our data is well indicative of the spectrum of COVID-19 infection among SCD cohort.
Conclusion SCD patients in India are not at increased risk of infection, clinical severity for COVID-19 infection. COVID-19 infection did not precipitate Vaso occlusive crises in SCD patients. Our data suggest that covered vaccination is safe in SCD patients.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
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