Overbeck Victoria, Taylor Bradford P, Turcinovic Jacquelyn, Qiu Xueting, Schaeffer Beau, Seitz Scott, Curry Scott R, Hanage William P, Connor John H, Kuppalli Krutika
Departments of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Heliyon. 2023 Dec 14;10(1):e23699. doi: 10.1016/j.heliyon.2023.e23699. eCollection 2024 Jan 15.
Immunocompromised patients receiving B-cell-depleting therapies are at increased risk of persistent SARS-CoV-2 infection, with many experiencing fatal outcomes. We report a successful outcome in a patient with rheumatoid arthritis (RA) on rituximab diagnosed with COVID-19 in July 2020 with persistent infection for over 245 days.
The patient received numerous treatment courses for persistent COVID-19 infection, including remdesivir, baricitinib, immunoglobulin and high doses of corticosteroids followed by a prolonged taper due to persistent respiratory symptoms and cryptogenic organizing pneumonia. Her clinical course was complicated by sinusitis with secondary bacteremia, and cytomegalovirus (CMV) viremia and pneumonitis. SARS-CoV-2 positive RNA samples were extracted from two nasopharyngeal swabs and sequenced using targeted amplicon Next-Generation Sequencing which were analyzed for virus evolution over time. Viral sequencing indicated lineage B.1.585.3 SARS-CoV-2 accumulated Spike protein mutations associated with immune evasion and resistance to therapeutics. Upon slowly decreasing the patient's steroids, she had resolution of her symptoms and had a negative nasopharyngeal SARS-CoV-2 PCR and serum CMV PCR in March 2021.
A patient with RA on B-cell depleting therapy developed persistent SARS-CoV-2 infection allowing for virus evolution and had numerous complications, including viral and bacterial co-infections with opportunistic pathogens. Despite intra-host evolution with a more immune evasive SARS-CoV-2 lineage, it was cleared after 245 days with reconstitution of the patient's immune system.
接受B细胞耗竭疗法的免疫功能低下患者持续感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的风险增加,许多患者出现致命后果。我们报告了一例类风湿关节炎(RA)患者的成功治疗结果,该患者在接受利妥昔单抗治疗,于2020年7月被诊断为冠状病毒病2019(COVID-19),持续感染超过245天。
该患者因COVID-19持续感染接受了多个疗程的治疗,包括瑞德西韦、巴瑞替尼、免疫球蛋白和高剂量皮质类固醇,由于持续的呼吸道症状和隐源性机化性肺炎,随后进行了长时间的减量。她的临床病程因鼻窦炎继发菌血症、巨细胞病毒(CMV)病毒血症和肺炎而复杂化。从两份鼻咽拭子中提取SARS-CoV-2阳性RNA样本,并使用靶向扩增子二代测序进行测序,分析病毒随时间的进化情况。病毒测序表明,B.1.585.3谱系的SARS-CoV-2积累了与免疫逃逸和对治疗药物耐药相关的刺突蛋白突变。在缓慢减少患者的类固醇剂量后,她的症状得到缓解,2021年3月鼻咽SARS-CoV-2聚合酶链反应(PCR)和血清CMV PCR结果均为阴性。
一名接受B细胞耗竭治疗的RA患者发生了持续的SARS-CoV-2感染,导致病毒进化,并出现了许多并发症,包括与机会性病原体的病毒和细菌合并感染。尽管宿主内进化出了更具免疫逃逸能力的SARS-CoV-2谱系,但在245天后随着患者免疫系统的重建,病毒被清除。