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Case report: Long-lasting SARS-CoV-2 infection with post-COVID-19 condition in two patients with chronic lymphocytic leukemia: The emerging therapeutic role of casirivimab/imdevimab
Frontiers in Oncology ( IF 4.7 ) Pub Date : 2022-09-30 , DOI: 10.3389/fonc.2022.945060
Laura Ballotta 1, 2 , Omar Simonetti 3 , Pierlanfranco D'Agaro 1, 4 , Ludovica Segat 4 , Raffaella Koncan 1, 4 , Pamela Martinez-Orellana 5 , Federica Dattola 5, 6 , Emanuele Orsini 5 , Alessandro Marcello 5 , Simeone Dal Monego 7 , Danilo Licastro 7 , Andrea Misin 3 , Sara Mohamed 2 , Eugenio Sbisà 2 , Elisa Lucchini 2 , Giovanni Maria De Sabbata 2 , Francesco Zaja 1, 2 , Roberto Luzzati 1, 3
Affiliation  

Post-coronavirus disease 2019 (post-COVID-19) condition, previously referred to as long COVID, includes a post-acute syndrome defined by the presence of non-specific symptoms occurring usually 3 months from the onset of the acute phase and lasting at least 2 months. Patients with chronic lymphocytic leukemia (CLL) represent a high-risk population for COVID-19. Moreover, the response to SARS-CoV-2 vaccination is often absent or inadequate. The introduction of monoclonal antibodies (mAbs) in the treatment landscape of COVID-19 allowed to reduce hospitalization and mortality in mild–moderate SARS-CoV-2 infection, but limited data are available in hematological patients. We here report the effective use of casirivimab/imdevimab (CI) in the treatment of two CLL patients with persistent infection and post-COVID-19 condition. Full genome sequencing of viral RNA from nasopharyngeal swabs was performed at the time of COVID-19 diagnosis and before the administration of CI. Both patients experienced persistent SARS-CoV-2 infection with no seroconversion for 8 and 7 months, respectively, associated with COVID symptoms. In both cases after the infusion of CI, we observed a rapid negativization of the nasal swabs, the resolution of post-COVID-19 condition, and the development of both the IgG against the trimeric spike protein and the receptor-binding domain (RBD) of the spike protein. The analysis of the viral genome in the period elapsed from the time of COVID-19 diagnosis and the administration of mAbs showed the development of new mutations, especially in the S gene. The genome variations observed during the time suggest a role of persistent SARS-CoV-2 infection as a possible source for the development of viral variants. The effects observed in these two patients appeared strongly related to passive immunity conferred by CI treatment permitting SARS-CoV-2 clearance and resolution of post-COVID-19 condition. On these grounds, passive anti-SARS-CoV-2 antibody treatment may represent as a possible therapeutic option in some patients with persistent SARS-CoV-2 infection.



中文翻译:

病例报告:两名慢性淋巴细胞白血病患者出现长期 SARS-CoV-2 感染并伴有 COVID-19 后病情:casirivimab/imdevimab 的新兴治疗作用

2019 年冠状病毒病后(COVID-19 后)病症,以前称为长期 COVID,包括急性后综合征,其定义为出现非特异性症状,通常在急性期开始后 3 个月内出现,并持续至至少2个月。慢性淋巴细胞白血病 (CLL) 患者是感染 COVID-19 的高危人群。此外,对 SARS-CoV-2 疫苗接种的反应往往不存在或不充分。在 COVID-19 治疗领域引入单克隆抗体 (mAb) 可以减少轻中度 SARS-CoV-2 感染的住院率和死亡率,但血液病患者的数据有限。我们在这里报告了卡西里维单抗/伊德维单抗(CI)在治疗两名持续感染和 COVID-19 后病情的 CLL 患者中的有效使用。在诊断 COVID-19 时和给予 CI 之前,对鼻咽拭子中的病毒 RNA 进行了全基因组测序。两名患者都经历了持续的 SARS-CoV-2 感染,并且分别在 8 个月和 7 个月内没有与新冠症状相关的血清转化。在这两种情况下,输注 CI 后,我们观察到鼻拭子的快速阴性、COVID-19 后病情的缓解以及针对三聚刺突蛋白和受体结合域 (RBD) 的 IgG 的产生刺突蛋白。对 COVID-19 诊断和单克隆抗体给药期间病毒基因组的分析显示,出现了新的突变,特别是在S基因。在此期间观察到的基因组变异表明,持续性 SARS-CoV-2 感染可能是病毒变异体发展的来源。在这两名患者中观察到的效果似乎与 CI 治疗赋予的被动免疫密切相关,从而清除 SARS-CoV-2 并解决 COVID-19 后的病情。基于这些理由,被动抗 SARS-CoV-2 抗体治疗可能是一些持续感染 SARS-CoV-2 的患者的一种可能的治疗选择。

更新日期:2022-09-30
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