Internationalism in climate action and China's role

The world is facing dual challenges of generating an economic recovery from the COVID-19 crisis, and transitioning to a low-carbon economy to tackle climate change. Strongly interrelated global challenges will require an integrated and coordinated response by all countries to manage the risk and lay the foundation for building back better. As the world's biggest emitter and the second-largest economy, China is a very important player in international collaboration and coordination in climate action. Against this backdrop, this paper looks into the increasingly crucial role that China is playing in global climate action, especially focusing on three aspects: China's domestic and foreign policymaking for the energy transition;its role in promoting multilateralism and international collaboration on building a sustainable world;and how it could accelerate climate action and diplomacy through research, development and innovation. In the critical decade of the 2020s, China has a great opportunity to further transform and upgrade its energy and industrial structures, promote research, development and the application of green and low-carbon technologies and intensify international climate cooperation on climate change. China should aim to be at the forefront of raising climate ambition and accelerating climate action for a sustainable and more equitable world. © 2023 IOP Publishing Ltd.

CLINICAL PROFILE OF COVID-19 INFECTION AND IMMUNE RESPONSE AFTER 3AND6 MONTH VACCINATION AGAINST SARS-COV-2 IN ADULT PATIENTS WITH TRANSFUSION-DEPENDENT THALASSAEMIATHE EXPERIENCE OF A GREEK CENTER

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).

REAL-WORLD DATA ON THE USE OF LUSPATERCEPT IN GREEK PATIENTS WITH TRANSFUSION DEPENDENT THALASSEMIA

Background: The EMA-approved, erythroid maturation agent, luspatercept, has been shown to decrease transfusion burden in patients with transfusion-dependent thalassemia (TDT). Aims: In this multicenter, retrospective cross-sectional study, real-world data from the use of luspatercept in TDT patients, managed in 5 major Thalassemia Centers in Greece are presented. Methods: Inclusion criteria included TDT patients, having received luspatercept as per approved indications for at least 3 months. Data cut-off date was 31/1/2022. We estimated the quantity of blood (in cc of Packed Red Blood Cells -PRBC) received over 12 weeks for the intervals: 12 weeks before starting treatment (baseline);1-12 weeks;5-16 weeks and 13-24 weeks post starting therapy. Changes in mean pre-transfusion hemoglobin (Hb), uric acid, creatinine, lactic acid dehydrogenase (LDH), white blood cells (WBC) and platelets counts were analyzed for these same respective periods. Adverse events (AE) were recorded. Statistical analysis performed with RStudio v.3.6.2. Results: Main results of the study are shown in Table 1. Forty-nine patients (median age: 46 years range:15-64, sex: M:F/33:16) received Luspatercept every 21 days. Data for weeks 5-16 and 13-24 were available for 30 and 16 patients, respectively. The initial dose of luspatercept was 1 mg/kg and increased selectively up to 1.25mg/kg based on tolerability and efficacy and according to guidelines. A statistically significant (p<0.005) decrease in PRBC transfused in all 12-weeks' intervals analyzed compared to baseline was observed. No statistically significant decrease of PRBC transfused was found between the intervals 5-16weeks and 13-24 weeks compared to the initial interval of 1-12 weeks. There was not a significant change for the mean pre-transfusion Hb compared to baseline. A statistically significant (p<0.005) increase in uric acid, creatinine, LDH , WBC and platelets was observed for the interval 1-12 weeks in comparison with baseline (mean: 6.42±1.64mg/dl vs 5.48±1.6mg/dl, 0.87±0.16mg/dl vs 0.83±0.18mg/dl, 352±205mg/dl vs 204±62mg/dl, 11.78x109 ±5.29x109/L vs 10.36x109±4.35x109/L, and 450x109±221x109/L vs 415x109±202x109/L, respectively. Similar difference was observed between the 13-24 weeks interval and baseline only for uric acid, LDH and platelets (mean: 6.28±1.41mg/dl vs 5.48±1.6mg/dl p=0.003, 406±301mg/dl vs 204±62mg/dl p=0.014, 467x109±226x109/L vs 415x109±202x109/L p<0.008 respectively). Twenty five out of 49 patients reported AE. The most common AE included bone pain 16/49 (32.6%) and fatigue 7/49 (14.2%). Frequent urination, headache, swelling at injection site, blurry vision, tearing, libido decrease, tachycardia, periorbital oedema, dizziness, and exacerbation of manic-depressive episodes were also reported. Twelve patients discontinued treatment. Reasons for discontinuation included: non-response to treatment (7 patients), adverse events (3 patients), non-compliance (1 patient), death due to COVID19 infection (1 patient). Summary/Conclusion: Real world data on the use of luspatercept in TDT parallel results from the trial, showing heterogeneous and lasting efficacy and acceptable toxicity. Longer follow up and increased number of patients are required to validate these initial observations. (Table Presented).

Adverse Events Following COVID-19 Vaccination in Transfusion-Dependent -Thalassemia Patients

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.