Thromboprophylaxis Outcome in Childhood SARS-Cov-2 Infection: A Single-Center Experience.

BACKGROUND: The SARS-CoV-2 infection has been associated with potentially endothelial damage and coagulation cascade activation that cause thrombosis. There is limited information on thrombosis and anticoagulant therapy in children with coronavirus disease 2019 (COVID-19). AIMS: This study evaluates the outcome of thromboprophylaxis in children younger than 18-year old with COVID-19 infection. METHODS: A retrospective study was conducted on 184 hospitalized pediatric patients with confirmed COVID-19 infection. A designed questionnaire was made to collect all demographic, clinical, and laboratory data. According to World Health Organization, the patients were classified as asymptomatic/mild, moderate, severe, and critically ill. RESULTS: The mean age of the patients was 7.04±5.9 (1 wk to younger than 18 y). Overall, 33 patients received anticoagulant therapy. All patients who passed away (n=19) belonged to the critical group. One patient (1.28%) was complicated with deep vein thrombosis despite taking thromboprophylaxis, and 1 (1.28%) with pulmonary thromboembolism while the patient did not take an anticoagulant. CONCLUSIONS: Our data showed a lower rate of thrombosis (1.4%) than adult patients with COVID-19. It may underline the role of anticoagulants in moderate to severe/critically ill children with COVID-19 infection. Expert opinion and personal experience are necessary, while we have a significant knowledge gap in understanding COVID-19-associated coagulopathy and thrombotic risk in children.

Efficacy and Safety of Sinopharm Vaccine for SARS-CoV-2 and breakthrough infections in Iranian Patients with Hemoglobinopathies: A Preliminary Report.

Background: The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to high morbidity and mortality worldwide. Vaccination against SARS-CoV-2 is a leading strategy to change the course of the COVID-19 pandemic. Aims of the study: Our aim was to investigate the efficacy and side effects of the Sinopharm vaccine in patients with hemoglobinopathies in Iran and the frequency of breakthrough infection after a full course of vaccination. Methods: A multicenter cross-sectional study of 434 patients with hemoglobinopathies (303 ß-thalassemia major, 118 ß-thalassemia intermedia, and 13 sickle-thalassemia) were conducted from March to July 2021 in IRAN. All patients have received the first dose of the China Sinopharm vaccine and received the second dose of the vaccine 28 days apar. Antibody testing: Detection of immunity after vaccination was evaluated by commercial enzyme-linked immunosorbent assay (Pishtazteb ELISA commercial kit), including a surrogate virus neutralization test (sVNT), for detection of SARS-CoV-2 immunoglobulins (IgA, IgM, IgG), total neutralizing antibody (NAb). Results: The mean age of patients was 35.0 ± 8.5 (from 18 to 70) years, and 55.6% were positive for the antibody. Overall, 48.2% of the studied population had at least one side effect after vaccination. The most frequent side effects were fever and chills, dizziness, and body pain. A total of 90 (20.7%) vaccinated patients developed breakthrough infections after two doses of Sinopharm vaccination. Disease severity was recorded, and it was classified as mild in 77.8%, moderate in 13.6%, and severe in 7.4% of patients. One 28-year-old woman with ß-thalassemia major died eight days after diagnosing a breakthrough SARS-CoV-2 infection. Conclusion: No safety concerns were identified in patients who received two doses of the Sinopharm vaccine. Its efficacy was not optimal due to the lack of effect on new variations of the virus. However, our data show that it seems to be protective against the severity of COVID-19 infection in patients with hemoglobinopathies. The frequency of breakthrough infections after two doses of Sinopharm vaccination supports the evolving dynamic of SARS-CoV-2 variants requiring special challenge since such infection may represent a risk for vulnerable patients.

Preliminary Data on COVID-19 in Patients with Hemoglobinopathies: A Multicentre ICET-A Study.

OBJECTIVES: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings, and outcomes of COVID-19 in patients with transfusion-dependent ß thalassemia major (TM), ß-thalassemia intermedia (TI) and sickle cell disease (SCD). DESIGN: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies, participated in the survey. MAIN OUTCOME DATA: Clinical, laboratory, and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized. RESULTS: A total of 13 patients, 7 with TM, 3 with TI, and 3 with SCD, with confirmed COVID-19, were identified in 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. Six patients had pneumonia, and 4 needed oxygen therapy. Increased C-reactive protein (6/10), high serum lactate dehydrogenase (LDH; 6/10), and erythrocyte sedimentation rate (ESR; 6/10) were the most common laboratory findings. 6/10 patients had an exacerbation of anemia (2 with SCD). In the majority of patients, the course of COVID-19 was moderate (6/10) and severe in 3/10 patients. A 30-year-old female with TM, developed a critical SARS-CoV-2 infection, followed by death in an Intensive Care Unit. In one Center (Oman), the majority of suspected cases were observed in patients with SCD between the age of 21 and 40 years. A rapid clinical improvement of tachypnea/dyspnea and oxygen saturation was observed, after red blood cell exchange transfusion, in a young girl with SCD and worsening of anemia (Hb level from 9.2 g/dl to 6.1g/dl). CONCLUSIONS: The data presented in this survey permit an early assessment of the clinical characteristics of COVID 19 in different countries. 70% of symptomatic patients with COVID- 19 required hospitalization. The presence of associated co-morbidities can aggravate the severity of COVID- 19, leading to a poorer prognosis irrespective of age.

Antithrombotic prophylaxis in children and adolescents' patients with SARS-CoV-2 (COVID-19) infection: A practical guidance for clinicians.

Severe coronavirus disease 2019 (COVID-19) is often associated with features of hypercoagulable state which can manifest as venous thromboembolism (VTE) and/or microthrombosis. Given the high risk of VTE in critically ill COVID-19 patients, appropriate VTE prophylaxis seems to be an important part of managing these patients. Although many protocols regarding venous thromboembolism (VTE) prophylaxis or therapeutic (full-dose) anticoagulation have been conducted worldwide, primarily in hospitalised adult patients, details on paediatric patients, if included, are limited or incomplete. The current evidences suggest that anticoagulation therapy with low molecular weight heparins (LMWH) appears to be associated with better prognosis in patients with moderate to severe COVID-19 induced coagulopathies or elevated D-dimer levels.  Our recommendations are intended to offer guidance for anticoagulation prophylaxis and treatment in COVID-19 children and adolescent patients and not intend to supersede the clinician judgement. We are also conscious that several clinical questions deserve further studies and clarifications because this area is rapidly evolving.

Prevalence and severity of Coronavirus disease 2019 (COVID-19) in Transfusion Dependent and Non-Transfusion Dependent ß-thalassemia patients and effects of associated comorbidities: an Iranian nationwide study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreak is a global and challenging disease that is accompany with mortality and morbidity. AIM OF STUDY: We evaluated the prevalence and the impact of comorbidities in thalassemia Iranian patients affected by COVID-19.  Methods: A multicenter, retrospective, cross-sectional study was conducted across all comprehensive thalassemia centers in Iran, from January to June 15th, 2020. RESULTS: Forty-three confirmed COVID-19 thalassemia patients (32 TDT, and 11 NTDT) were detected. The mean age of patients was 35.3 ± 11.5 years (range 9 - 67); 21 females and 22 males. Overall, 78.1% of TDT and 90.9% of NTDT patients were complicated with at least one comorbidity (P: 0.656). The overall mortality rate of thalassemia patients with COVID-19 was 18.6% while 27.3% was in NTDT patients compared to 15.6% in TDT patients (P:0.401). The dead group had a non-significant higher frequency of endocrinopathies compared to the recovered group (62.5% versus 45.7% P:0.457). Ten female thalassemia patients with positive COVID-19 had hypogonadism, six patients were receiving hormone replacement therapy and all of them recovered (zero death) compared to two deaths from 4 patients who were not receiving hormone replacement therapy (P:0.133). Furthermore, the prevalence of COVID-19 in NTDT patients was significantly higher than the general population (45 per 10,000 versus 22.29 per 10,000 respectively, P:0.018) while the prevalence of TDT was almost similar to the normal population (P:0.539). The mortality rate of COVID-19 was 4.71% in the normal Iranian population compared to 18.6% in ß-thalassemias (P: <0.001) at the same date. CONCLUSIONS: It is important to acknowledge that ß-thalassemia patients, especially young adults/adults, have a chronic condition which may contribute to increase susceptibility to SARS-CoV-2 infection. A higher susceptibility to the infection was observed in patients with NTDT and in untreated hypogonadal female thalassemic patients. However, to confirm these data, more accurate designed studies are needed.

A comprehensive update of ICET-A Network on COVID-19 in thalassemias: what we know and where we stand.

A review of the literature on COVID-19 pandemic in patients with thalassemias is presented. Globally, the prevalence of COVID-19 among  ß-thalassemia patients seems to be lower than in general population; associated co-morbidities aggravated the severity of  COVID- 19, leading to a poorer prognosis, irrespective of age. A multicenter registry will enhance the understanding of COVID-19 in these patients and will lead to more evidence-based management recommendations.