ABSTRACT
Background: Patients with transfusion-dependent-thalassaemia (TDT) are considered as increased risk population for severe and/or morbid COVID-19 infection. Timely vaccination is the main preventive method for severe COVID-19. Aims: To provide an overview of the clinical profile and outcome of COVID-19 infection in patients with TDT as well as to study the immune response after 3 and 6 months after vaccination against COVID-19 in adult patients with transfusion-dependent thalassaemia. Methods: This analysis focused on the evaluation in TDT patients on the long-term immune response post vaccination and on the course of COVID-19 infection and its correlation with immunization status. Serum was collected at 4 pre-defined time points, namely, just before 1st dose (TP1), 7 weeks after the 1st dose (TP2), 3 months (TP3) and 6 months (TP4) after 2nd dose. Neutralizing antibodies (NAbs) against SARS-CoV-2 were measured using FDA-approved methods. According to manufacturer, the scale of NAbs titer is 0-100%, with ≥30% considered as positive and ≥50% as clinically relevant viral inhibition. Age-matched healthy volunteers (median age: 46 years, range: 24-64 years, 24 males / 53 females) who received mRNA vaccines served as the control group for NAbs evaluation. Results: 340 (170female/170male) TDT patients older than 18 years (mean 43.6±11.5 years) followed in a single unit were included in the analysis. 270 patients (79%) were vaccinated with 2 or 3 doses. Immune response to vaccination was evaluated in 90 patients (median age: 46 years, range: 19-63 years, 40 males / 50 females). NAbs were at the level of non-immunity in all the patients at baseline (TP1) (mean 16.57% ±11.85) and showed a significant increase after the second dose (TP2) mean 86.96%±12.95 (p<0.0001). At TP3 and TP4 Nabs showed a significant decrease but remained in protective levels for the majority of the patients (mean 88.75% ±9.7 and 74.64% ±17.2 respectively(p<0.0001). The kinetics of NAbs were similar to controls except for levels at TP4 (p=0.02) (Figure 1). Up to 10/FEB/2022, 43 TDT patients (median age 43.52 range 18.6-57.9 years) were diagnosed with COVID-19, with 1 of them being infected twice. Of them, 17 were unvaccinated, 18 had received 2 doses of vaccine, while 8 had received 3 doses of the vaccine. The incidence rate was 9.6% and 24.3% for vaccinated and unvaccinated patients, respectively. The severity of the COVID-19 for vaccinated and unvaccinated patients were as follows, respectively, ;Grade 1 (asymptomatic): 0 and 1, Grade 2 (mild symptoms, symptomatic therapy, no COVID19 specific therapy): 23 and 9, Grade 3 (mild symptoms, symptomatic therapy, with COVID19 specific therapy): 1 and 3, Grade 4 (moderate: pneumonia, thrombophlebitis, Hospitalization): 2 and 3, Grade 5 (Hospitalization requiring ICU, death): 0 and 1. Thrombotic event was documented in 1 patient. All patients except one from unvaccinated group are alive. Summary/Conclusion: Immune response to vaccination may wean faster in TDT patients. in Unvaccinated TDT patients were more likely to be infected and to develop more serious COVID-19 infection compared to vaccinated patients. (Figure Presented).
ABSTRACT
Introduction: Patients with transfusion-dependent-thalassemia (TDT) are considered as increased risk population for severe and/or morbid COVID-19 infection. Timely vaccination is the main preventive method for severe COVID-19. Different adverse events and reactions following vaccination have been reported, with severe ones being extremely rare. TDT patients may have altered immunity due to chronic transfusions, iron overload and chelation therapy, and splenic dysfunction. The safety profile of vaccination in chronically transfused patients with thalassemia has not been reported. AIM: To evaluate the safety profile of COVID-19 vaccines in TDT patients. Patients and Methods: This is a single institution's, retrospective analysis evaluating all TDT patients, older than 18 years old, who had completed the vaccination protocol at least 30 days before data cut-off time (July 20 th 2021). Adverse events were reported by patients up to 30 days post each dose. Demographic data and hematological data, including mean hemoglobin levels before and up to 30 days after each dose, were recorded. T-test was performed to investigate changes in hematological profile and transfusion burden post vaccination. Results: 186 patients (median age:45;range:18-61 years old;male/female:87/99) were included for data analysis corresponding to 53% of all TDT patients followed in our Thalassemia Unit. Distribution of vaccine types were: Comirnaty -BNT162b2 (Pfizer Inc. and BioNTech)90.86% (n =168), Vaxzevria (previously COVID-19 vaccine, AstraZeneca)1.61% (n=3), Moderna (Moderna TX Inc.)6.99% (n =13) and JNJ-78436735 (Janssen Pharmaceuticals Companies of Johnson & Johnson)0.54% (n =2). No patients had confirmed or suspected previous COVID-19 infection. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The incidence of adverse events after 1 st and 2 nd dose were 43.5% (81/186) and 54.8% (102/186), respectively. Adverse events after 1 st dose included pain at injection site 26.3%( n=49), fatigue 9.7%(n=18), fever 5.4% (n=10),headaches 4.3% (n=8), arthralgia and myalgia 2.2% (n=4), and lymphadenopathy 0.5% (n=1). Adverse events after 2 nd dose included fever 28.5% (n=53), fatigue 17.7% (n=33), pain at injection site 15.6%(n=29), arthralgia and myalgia 11.3% (n=21), headaches 9.1% (n=17), lymphadenopathy 3.2% (n=6), dizziness 0,5% (n=1), tachycardia 0.5% (n=1), diarrhea/ vomiting 0.05% (n=1) and amaurosis fugax 0.5%: (n=1). No grade 4-5 events or anaphylaxis were observed. Two patients (both males, 51 years and 45 years old, respectively) presented with acute hemolytic crisis with hemoglobinuria in 3 rd and 20 th day after the second dose with Pfizer/BioNTech, respectively. They are receiving treatment with corticosteroids without partial response. Both patients had a history of acute hemolysis crisis within the last 3 years. A decrease in Hb levels after either the first or second dose compared to pre-vaccination mean Hb levels was observed (mean=9.9 /sd=0.63 vs mean=9.44 /sd=0.76), (p < 0.001). Conclusions: Compared to the vaccine trials, we observed some lower incidence of vaccine-related adverse events in our cohort of TDT patients, which may be related to the less stringent reporting methods outside official trials. A temporary drop in hemoglobin levels may be noted in chronically transfusion patients, which parallels what is observed when patients are developing infection or inflammation. Of interest, two patients with previous history of alloimmunization, developed hemolysis. Close hematological follow up may be required in TDT patients post vaccination. The risk/benefit of the vaccination is strongly positive for this vulnerable population. Disclosures: Kattamis: Agios Pharmaceuticals: Consultancy;IONIS: Consultancy;VIFOR: Consultancy;CRISPR/Vertex: Consultancy, Honoraria;BMS/Celgene: Consultancy, Honoraria, Research Funding;Chiesi: Honoraria;Novartis: Consultancy, Honoraria, Research Funding;Amgen: Consultancy.