CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunocompromised patients with persistent SARS-CoV-2 viral shedding ≥8 weeks, clinical outcomes, and virological dynamics: a retrospective multicenter cohort study, 2020-2024.
Immunocompromised patients with persistent SARS-CoV-2 viral shedding ≥8 weeks, clinical outcomes, and virological dynamics: a retrospective multicenter cohort study, 2020-2024.
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免疫功能低下患者(ICPs)感染 SARS-CoV-2 后发生重症的风险更高。部分患者出现持续超过八周的病毒排毒,这与死亡率增加和侵袭性真菌感染相关。
然而,针对这些患者的临床特征、治疗影响及标准化管理的数据仍然有限。我们在 Groupe Hospitalier Paris Centre 开展了一项回顾性队列研究,时间范围为 2020 年 3 月 1 日至 2024 年 2 月 10 日。
我们评估了伴有持续性 SARS-CoV-2 排毒(>8 周)的有症状 ICPs,分析了临床进展、病毒清除时间以及与治疗方案相关的耐药突变出现情况。共纳入 53 例患者:53% 为实体器官移植(SOT)受者,42% 患有血液系统恶性肿瘤(HMs),5% 患有其他免疫抑制状态。重症感染发生率为 32%,91% 需要住院治疗,17%(n = 9)出现侵袭性霉菌感染。SOT 受者比 HM 患者更快实现临床治愈(P < 0.01)。接受直接抗病毒药物治疗的患者病毒清除速度显著快于接受单克隆抗体(mAbs)或恢复期血浆治疗的患者(P = 0.03)。未出现针对 remdesivir 或 nirmatrelvir/ritonavir 的耐药突变。
然而,54% 的病毒株对 mAbs 表现出初始或获得性刺突蛋白耐药。直接抗病毒治疗,尤其是 remdesivir 和 nirmatrelvir/ritonavir,在促进伴有持续性有症状 SARS-CoV-2 感染的 ICPs 实现更快病毒清除和临床恢复方面似乎安全且有效。
Immunocompromised patients (ICPs) infected with SARS-CoV-2 are at higher risk of severe illness. Some experience persistent viral shedding beyond eight weeks, which is associated with increased mortality and invasive fungal infections.
However, data on the clinical profile, treatment impact, and standardized management for these patients remain limited.
We conducted a retrospective cohort study at Groupe Hospitalier Paris Centre between March 1, 2020, and February 10, 2024.
We assessed symptomatic ICPs with persistent SARS-CoV-2 shedding (>8 weeks), analyzing clinical progression, time to viral clearance, and emergence of resistance mutations in relation to treatment regimens. Fifty-three patients were included: 53% were solid organ transplant (SOT) recipients, 42% had hematological malignancies (HMs), and 5% had other immunosuppressive conditions.
Severe infections occurred in 32%, 91% required hospitalization, and 17% ( n = 9) presented invasive mold infections. SOT recipients achieved clinical cure faster than HM patients ( P < 0. 01). Patients treated with direct antivirals showed significantly faster viral clearance ( P = 0. 03) than those treated with monoclonal antibodies (mAbs) or convalescent plasma. No resistance mutations emerged against remdesivir or nirmatrelvir/ritonavir.
However, 54% of viral strains showed initial or acquired spike protein resistance to mAbs. Direct antiviral therapies, particularly remdesivir and nirmatrelvir/ritonavir, appear safe and effective in promoting faster viral clearance and clinical recovery in ICPs with persistent symptomatic SARS-CoV-2 infection.
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