Braitsch Krischan, Jeske Samuel D, Stroh Jacob, Hefter Maike, Platen Louise, Bachmann Quirin, Renders Lutz, Protzer Ulrike, Götze Katharina S, Herhaus Peter, Verbeek Mareike, Spinner Christoph D, Bassermann Florian, Högner Marion, Haller Bernhard, Schneider Jochen, Heider Michael
TUM School of Medicine and Health, Department of Internal Medicine III, University Medical Center, Technical University of Munich, 81675 Munich, Germany.
TUM School of Medicine and Health, Institute of Virology, University Medical Center, Technical University of Munich, 81675 Munich, Germany.
Vaccines (Basel). 2024 Aug 1;12(8):871. doi: 10.3390/vaccines12080871.
Patients with hematologic malignancies still face a significant risk of severe coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-neutralizing monoclonal antibody combination tixagevimab/cilgavimab (TIX/CGB) could be administered to immunocompromised patients for pre-exposure prophylaxis (PrEP) before the emergence of TIX/CGB-resistant COVID-19 Omicron variants. TIX/CGB application could be carried out regardless of the host's immune response to previous active SARS-CoV-2 vaccinations or infections. Because the efficacy of COVID-19 PrEP remains unclear, especially in SARS-CoV-2-seropositive patients, German national guidelines recommended TIX/CGB PrEP only for SARS-CoV-2-seronegative patients in addition to an intensified active vaccination schedule. Having followed these guidelines, we now report the characteristics and outcomes of 54 recipients of TIX/CGB PrEP in SARS-CoV-2-seronegative patients with hematological disease from a German tertiary medical center and compare them to 125 seropositive patients who did not receive any PrEP. While the number of patients with B-cell lymphomas was significantly higher in the seronegative cohort (33 (61%) vs. 18 (14%) cases, < 0.01), patients with myeloid diseases were significantly more frequent in the seropositive cohort (51 (41%) vs. 5 (9%) cases, < 0.01). Strikingly, patients who had undergone allogeneic hematopoietic stem cell transplantation were significantly more likely (forty-nine (39%) vs. six (11%) cases, < 0.01) to be SARS-CoV-2 seropositive. We observed that prophylactic application of TIX/CGB PrEP to a highly vulnerable group of SARS-CoV-2-seronegative patients resulted in a similar number of COVID-19 breakthrough infections compared to the untreated seropositive control group (16 (32%) vs. 39 (36%), = 0.62) and comparable COVID-19-related outcomes like hospitalization and oxygen requirement throughout an extended follow-up period of 12 months. In conclusion, our results support the tailored approach of administering TIX/CGB PrEP only to SARS-CoV-2-seronegative patients during the COVID-19 pandemic and might provide a rationale for similar strategies during future outbreaks/diseases, especially in times of initial limited availability and/or financial constraints.
血液系统恶性肿瘤患者仍然面临着感染2019冠状病毒病（COVID-19）重症的重大风险。严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）中和单克隆抗体组合替沙格韦单抗/西加韦单抗（TIX/CGB）可在对TIX/CGB耐药的COVID-19奥密克戎变异株出现之前，用于免疫功能低下患者的暴露前预防（PrEP）。无论宿主对先前的SARS-CoV-2主动疫苗接种或感染的免疫反应如何，均可应用TIX/CGB。由于COVID-19 PrEP的疗效尚不清楚，尤其是在SARS-CoV-2血清学阳性患者中，德国国家指南建议，除了强化主动疫苗接种计划外，TIX/CGB PrEP仅用于SARS-CoV-2血清学阴性患者。遵循这些指南后，我们现在报告了德国一家三级医疗中心54例接受TIX/CGB PrEP的SARS-CoV-2血清学阴性血液系统疾病患者的特征和结局，并将其与125例未接受任何PrEP的血清学阳性患者进行比较。虽然血清学阴性队列中B细胞淋巴瘤患者的数量显著更高（33例（61%）对18例（14%），<0.01），但血清学阳性队列中髓系疾病患者更为常见（51例（41%）对5例（9%），<0.01）。引人注目的是，接受过异基因造血干细胞移植的患者SARS-CoV-2血清学阳性的可能性显著更高（49例（39%）对6例（11%），<0.01）。我们观察到，与未治疗的血清学阳性对照组相比，对一组高度易感染的SARS-CoV-2血清学阴性患者预防性应用TIX/CGB PrEP导致的COVID-19突破性感染数量相似（16例（32%）对39例（36%），=0.62），并且在长达12个月的延长随访期内，COVID-19相关结局如住院和吸氧需求相当。总之，我们的结果支持在COVID-19大流行期间仅对SARS-CoV-2血清学阴性患者采用TIX/CGB PrEP的针对性方法，并可能为未来疫情/疾病期间的类似策略提供理论依据，特别是在初始供应有限和/或资金紧张时期。
