Nagai Hiroyuki, Saito Makoto, Adachi Eisuke, Sakai-Tagawa Yuko, Yamayoshi Seiya, Kiso Maki, Kawamata Toyotaka, Koga Michiko, Kawaoka Yoshihiro, Tsutsumi Takeya, Yotsuyanagi Hiroshi
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Japan.
Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Japan.
Jpn J Infect Dis. 2022 Nov 22;75(6):608-611. doi: 10.7883/yoken.JJID.2022.092. Epub 2022 Jun 30.
Immunocompromised patients are more likely to develop severe COVID-19, and exhibit high mortality. It is also hypothesized that chronic infection in these patients can be a risk factor for developing new variants. We describe a patient with prolonged active infection of COVID-19 who became infected during treatment with an anti-CD20 antibody (obinutuzumab) for follicular lymphoma. This patient had persistent RT-PCR positivity and live virus isolation for nine months despite treatment with remdesivir and other potential antiviral therapies. The computed tomography image of the chest showed that the viral pneumonia repeatedly appeared and disappeared in different lobes, as if a new infection had occurred continuously. The patient's SARS-CoV-2 antibody titer was negative throughout the illness, even after two doses of the BNT162b2 mRNA vaccine were administered in the seventh month of infection. A combination of monoclonal antibody therapy against COVID-19 (casirivimab and imdevimab) and antivirals resulted in negative RT-PCR results, and the virus was no longer isolated. The patient was clinically cured. During the 9-month active infection period, no fixed mutations in the spike (S) protein were detected, and the in vitro susceptibility to remdesivir was retained. Therapeutic administration of anti-SARS-CoV-2 monoclonal antibodies is essential in immunocompromised patients. Therefore, measures to prevent resistance against these key drugs are urgently needed.
免疫功能低下的患者更易发展为重症新型冠状病毒肺炎（COVID-19），且死亡率较高。也有假设认为，这些患者的慢性感染可能是产生新变种的一个风险因素。我们描述了一名COVID-19持续活跃感染的患者，该患者在接受抗CD20抗体（奥妥珠单抗）治疗滤泡性淋巴瘤期间被感染。尽管接受了瑞德西韦及其他潜在抗病毒治疗，该患者的逆转录聚合酶链反应（RT-PCR）持续呈阳性且活病毒分离持续了9个月。胸部计算机断层扫描图像显示，病毒性肺炎在不同肺叶反复出现和消失，就好像不断有新的感染发生。在整个病程中，该患者的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）抗体滴度均为阴性，即使在感染后第7个月接种了两剂BNT162b2信使核糖核酸（mRNA）疫苗后也是如此。抗COVID-19单克隆抗体疗法（卡西瑞单抗和依德维单抗）与抗病毒药物联合使用后，RT-PCR结果转为阴性，且未再分离出病毒。该患者临床治愈。在9个月的活跃感染期内，未检测到刺突（S）蛋白的固定突变，且对瑞德西韦的体外敏感性得以保留。在免疫功能低下的患者中，抗SARS-CoV-2单克隆抗体的治疗性给药至关重要。因此，迫切需要采取措施防止对这些关键药物产生耐药性。
