key: cord-0984796-rc8us6mm authors: Kakkar, Shruti; Anand, Vaneet; Kapoor, Rashmi; Sidhi, Sukhmani; Grewal, Amanat; Chawla, Mehak; Goraya, J. S. title: Home isolation in transfusion-dependent thalassemia patients with SARS CoV2 infection: Experience from a developing country date: 2022-04-19 journal: Pediatric Hematology Oncology Journal DOI: 10.1016/j.phoj.2022.04.024 sha: b05ca486aa5cc874f7b62cce59845427407026a5 doc_id: 984796 cord_uid: rc8us6mm nan Coronavirus Introduction: Coronavirus disease (COVID-19), an infectious disease caused by the newly discovered novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared a pandemic by World Health Organization (WHO) in March 2020. [1] This disease posed unparallel challenges to the healthcare system, jeopardizing the lives of thousands of patients with hemoglobin disorders. In India, 34,544,882 people have been infected with SARS-CoV2 and 466,980 have died. [2] Patients with pre-existing co-morbidities including obesity, cardiovascular diseases, diabetes mellitus, immunodeficiency states, and chronic liver and kidney diseases were ascertained to be at increased risk of mortality from coronavirus disease. Thalassemia, an inherited hemoglobin disorder, is the commonest monogenic disorder that requires intensive life-long therapy and regular follow-up [3] . There is conflicting evidence on the outcome of COVID-19 in patients with thalassemia. Various authors have suggested that patients with thalassemia may be immune to SARS-CoV2 due to the absence of the potential target of the SARS-CoV2 virus and iron chelation therapy may also protect the patients against severe COVID 19 diseases due to anti-inflammatory and immunomodulatory effects. On the contrary, iron overload and its complications predispose the patients to a higher risk of severe COVID [4] [5] [6] . Studies from various parts of the world have shown an increased risk of mortality in patients with thalassemia. [7] [8] [9] We share our experience of managing patients with transfusion-dependent thalassemia with SARS-CoV2 in a resourcelimited setting. Aims and objectives: 1. To describe the clinical features of COVID-19 in patients with transfusion-dependent thalassemia. 2. To assess the feasibility of home base management of mild COVID-19 in patients with transfusion-dependent thalassemia. A retrospective study was conducted in the Thalassemia Day Care Centre of a tertiary care center in Punjab after obtaining approval from the Institutional Ethics Committee. The patients with transfusion-dependent thalassemia who tested positive for SARS-CoV2 by reverse transcriptase polymerase chain reaction (RTPCR) were included in the study. Consent was obtained before enrolment in the study. The data on patients' demographics including age, gender, height, weight, and body mass index (BMI); clinical characteristics including splenectomy status, associated complications, treatment given, and disease outcome and laboratory findings including hemoglobin, Creactive protein (CRP), D-dimer, renal functions, liver functions, and imaging studies were collected from the patient records in predesigned proforma. Testing for SARS-CoV2 was performed only if a patient had symptoms of the disease or had been exposed to someone with SARS-CoV2 infection or as a part of screening for the hospital admission. No routine testing was performed before transfusion. Patients were riskstratified as per the Thalassemia International Federation (TIF) risk assessment guidelines and the guidelines for the assessment of COVID-19 disease issued by the Ministry of Health and Family Welfare (MoHFW), Government of India. [10] [11] [12] [13] [14] Patients with mild COVID 19 were managed at home whereas those with moderate to severe COVID-19 were admitted. A baseline complete blood film, liver, and renal functions were done at the time of sending COVID-19 RTPCR. Patients managed at home were followed up daily by a dedicated hemoglobinopathy nurse. Daily temperature and oxygen saturation (SpO2) recording charts were maintained till defervescence of fever. Patients obtained the home kits (Fateh Kit) issued by the Government of Punjab [15] . As per the existing guidelines, patients received zinc, multivitamins, and Ivermectin/ doxycycline at home. Steroids were reserved for patients with moderate to severe COVID-19 disease and Vitamin C was not given to any of the patients. Patients were called for transfusion after they were RTPCR negative/ 10-14 days from the date of positive RTPCR as per the existing guidelines from the MoHFW, Government of India. [11-14] Iron chelation was held temporarily during the duration of fever for the first 3 patients, however, the subsequent patients continued deferasirox during COVID-19 illness. Imaging was performed only if the patient developed moderate to severe COVID-19 illness. The data has been described in terms of range; mean ± standard deviation (± SD), median, frequencies (number of cases), and relative frequencies (percentages) as appropriate. All statistical calculations will be done using (Statistical Package for the Social Science) SPSS 21version (SPSS Inc., Chicago, IL, USA) statistical program for Microsoft Windows Results: The thalassemia unit of the hospital provides regular transfusion services to 250 patients with transfusion-dependent thalassemia, 14 (0.06%) of whom had documented COVID -19 infection. The mean age of patients infected with SARS-CoV2 in our cohort was 18.9 ± 6.7 years with a range of 4-29 years. The male: female ratio was 6:1. The mean BMI in our study group was 18.5 ± 2.7 kg/m 2 . The baseline characteristics of the study group are described in Table 1 . Risk stratification at the time of diagnosis with COVID-19 disease was done as per the TIF guidelines. There were 5 patients each in low-risk (Group A1) and high-risk (Group B), and 4 patients were at Highest-risk (Group C). There was no patient with Moderate risk (Group A2) ( Table 2 ). Eight patients were tested due to the presence of symptoms attributable to COVID-19 disease, 4 were tested due to a history of exposure, and 2 patients tested positive during screening for admission for management of fracture femur and pain abdomen respectively. The most common presenting complaint in the study group was fever (64.3 % of patients) followed by fatigue (35.7% of the patients). Other chief complaints were headache, sore throat, loss of taste and smell, and vomiting. One patient complained of shortness of breath and reported desaturation at room air during home monitoring. Two patients required hospitalization due to COVID 19 disease. One of these patients had severe cardiac iron overload with diabetes mellitus and the other patient had desaturation (<94%) on room air at home. The patient had aggravation of anemia and no desaturation was reported after packed cell transfusion. Computed tomography of the chest did not show any evidence of COVID pneumonia and the child was discharged after 48 hours of observation. The child received 2 units of packed red blood cells during the hospital stay. Three more patients experienced an exacerbation of anemia requiring admission for blood transfusion as a day-care treatment. None of the patients required admission to intensive care or ventilation. Oxygen therapy and steroids were used for the patient with desaturation on room air. Ivermectin, doxycycline, and hydroxychloroquine were used for 3 patients each as per the existing guidelines of MoHFW, Government of India. None of the patients were prescribed remdesivir and tocilizumab. Iron chelation therapy was withheld in the patient with severe cardiac iron overload and diabetes mellitus. The patient presented to the emergency one-month post-discharge with cardiac arrhythmia and shock. He was given cardioversion and started on adenosine. The patient was discharged after stabilization on beta-blockers and intensive iron chelation with intravenous desferrioxamine. The current study attempts to fill the knowledge gap in the management of COVID-19 in thalassemia patients. There is not much evidence on the severity of COVID 19 and its management in this subset of patients. The current infection rate of COVID-19 is 30,045 patients per million population in India (0.03%). The infection rate in our TDCC was 0.06% (14/250) which is nearly double the general population in India. This may be due to increased chances of exposure to the infection with frequent hospital visits for blood transfusions. Most patients in our cohort were either asymptomatic or had mild COVID disease with symptoms like fever, fatigue, and sore throat similar to the observation made by other authors. [8, 19] A systemic review also showed that 82.4% of people were hospitalized for management and oxygen support was needed for 29.3% of the patients whereas only 2 patients (14.2%) needed hospitalization and one (7.1%) needed oxygen support in our cohort. The remaining 12 (85.7%) patients were effectively managed at home with regular telephonic monitoring. Thus, the underlying diagnosis of transfusion-dependent thalassemia did not lead to excess morbidity and mortality in our cohort. Hydroxychloroquine/ Ivermectin are not indicated for the management of COVID-19 as per recent reviews. [11, 12, 13] . However, they were used in some of our patients when they were included in the guidelines issued by the health ministry. Two patients in our study population were hospitalized for management of COVID-19. Iron chelation was stopped for the first patient who was diagnosed as COVID-19 positive in March 2020 as there was no experience in managing COVID 19 at that time and the effect of chelation on COVID-19 was unknown. The patient remained hospitalized for 18 days till his 2 specimens for RTPCR came back negative. As this patient already had severe cardiac iron overload, withholding the iron chelation proved detrimental and the patient developed cardiac arrhythmias in a month. Subsequent patients with COVID-19 continued to take iron chelation with deferasirox and recovered without any adverse effects. However, deferiprone was stopped due to fear of agranulocytosis in presence of a viral infection. Various studies have demonstrated an increased risk of morbidity and mortality in patients with coexisting comorbidities. Patients with advancing age were more likely to need hospital admission ( Table 3 ). The younger mean age of our patients may be a reason for better outcomes in this group. During the second wave of COVID 19 when the entire country was reeling under the lack of oxygen and hospital beds, our ability to manage patients at home helped in better utilization of resources. Only patients with moderate to severe COVID disease needed admission. The underlying diagnosis of transfusion-dependent thalassemia did not lead to excess morbidity and mortality in our cohort. World Health Organization. Coronavirus disease 2019 (COVID-19): situation report, 51 Guidelines for the management of transfusion dependent thalassaemia (TDT). 3 rd Edition. Cyprus, Nicosia: Thalassemia International Federation COVID-19: beta-thalassemia subjects immunised Beta-thalassemia may protect against COVID 19 Commentary: Could iron chelators prove to be useful as an adjunct to COVID-19 Treatment Regimens? β-Thalassemia Major and Coronavirus-19, Mortality and Morbidity: a Systematic Review Study COVID 19 and Hemoglobinopathies: Update of the Italian Experience COVID-19 and thalassemia beta major in splenectomized patient: Clinical case progression and literature review COVID-19 & Haemoglobin Disorders: A Classification of Risk Groups & Other Considerations (2020) -TIF Ministry of Health and Family Welfare, Government of India. Discharge Policy of nCoV Case Ministry of Health and Family Welfare, Government of India. Revised National Clinical Management Guideline for COVID 19 Updated Revised Discharge Policy for COVID 19 Ministry of Health and Family Welfare, Government of India Punjab CM launches Fateh kits for COVID patients in hospital and home isolation 19 treatment guidelines/Antiviral therapy/Chloroquine or Hydroxychloroquine and/or Azithromycin 19 treatment guidelines/Antiviral therapy/Ivermectin Acknowledgments: Patients with thalassemia and their families for being a part of this study. Hemoglobinopathy nurses Mrs. Balwinder Kaur and Baljit Kaur for diligently following up with the patients during home isolation. Child psychologist Priyanka Dewan for counseling the patients during home isolation and keeping their morale high. J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f