Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Transpl Infect Dis. 2023 Apr;25(2):e14055. doi: 10.1111/tid.14055. Epub 2023 Mar 16.
Transplant and hematologic malignancy patients have high Coronavirus disease 2019 (COVID-19) mortality and impaired vaccination responses. Omicron variant evades several monoclonal antibodies previously used in immunocompromised patients. Polyclonal COVID-19 convalescent plasma (CCP) may provide broader neutralizing capacity against new variants at high titers. Vaccination increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer in convalescent donors.
We conducted a retrospective chart review of hospitalized immunocompromised patients with COVID-19 who received high-titer CCP during the first omicron surge, collected from vaccinated donors within 6 months of pre-omicron COVID-19. Data on safety and outcomes were extracted.
A total of 44 immunocompromised patients were included, 59.1% with solid organ transplant, 22.7% with hematopoietic cell transplant, 11.4% with hematologic malignancy, and 6.8% with autoimmune disease. Overall, 95% of CCP units transfused were from recently recovered and vaccinated donors and had SARS-CoV-2 antibody results 8- to 37-fold higher than the Food and Drug Administration's cutoff for high-titer CCP. There were two mild transfusion reactions. A total of 30-day mortality was 4.5%. There were no differences in 100-day mortality by underlying diagnosis, levels of immunosuppression, and timing of CCP administration. Patients with higher immunosuppression had significantly higher mean World Health Organization clinical progression scores at 30-day post-CCP compared to those with lower immunosuppression.
CCP is a safe, globally available treatment for immunocompromised patients with COVID-19. Mortality was lower in our cohort than that of COVID-19 patients with similar immunocompromising conditions. Post-vaccine CCP with very high titers should be prioritized for study in immunocompromised patients. Post-vaccine CCP has the potential to keep pace with new variants by overcoming mutations at sufficiently high titer.
移植和血液恶性肿瘤患者的 2019 年冠状病毒病(COVID-19)死亡率较高,疫苗接种反应受损。Omicron 变体逃避了以前用于免疫功能低下患者的几种单克隆抗体。多克隆 COVID-19 恢复期血浆(CCP)可能以高滴度提供针对新变体的更广泛中和能力。疫苗接种会增加恢复期供体中严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)滴度。
我们对在首次 Omicron 浪涌期间接受高滴度 CCP 的住院免疫功能低下的 COVID-19 患者进行了回顾性图表审查,这些患者来自在 Omicron 之前的 COVID-19 6 个月内接种疫苗的供体。提取安全性和结果数据。
共纳入 44 例免疫功能低下的患者,其中 59.1%为实体器官移植患者,22.7%为造血细胞移植患者,11.4%为血液恶性肿瘤患者,6.8%为自身免疫性疾病患者。总体而言,输注的 CCP 中有 95%来自最近康复和接种疫苗的供体,SARS-CoV-2 抗体结果是食品和药物管理局高滴度 CCP 截止值的 8-37 倍。有 2 例轻度输血反应。30 天死亡率为 4.5%。基础诊断、免疫抑制程度和 CCP 给药时间不同,100 天死亡率无差异。与免疫抑制程度较低的患者相比,30 天 CCP 后,免疫抑制程度较高的患者的平均世界卫生组织临床进展评分显著更高。
CCP 是 COVID-19 免疫功能低下患者的一种安全、全球可用的治疗方法。我们的队列中的死亡率低于具有类似免疫缺陷条件的 COVID-19 患者。应优先研究具有非常高滴度的疫苗后 CCP 用于免疫功能低下的患者。疫苗后 CCP 具有通过足够高的滴度克服突变而跟上新变体的潜力。