Prolonged Novel Coronavirus 2019 Infection with Negative Immunoglobulins in a Patient on Obinutuzumab

J. Wang, A. Abburi, G. Molina-Pallete
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Abstract

Introduction: The novel coronavirus 2019 (COVID-19) infection is a worldwide pandemic. The clinical course is highly variable. Most patients recover with humoral and cell mediated immunities against reinfection. Previous studies showed immunocompetent patients with severe infections all became seropositive for immunoglobulins against COVID-19, while only a minority of patients with mild infections remained seronegative. However, immunocompromised patients can remain seronegative for up to two months with severe infections while shedding active virus. This case describes a patient on obinutuzumab who has persistently positive SARS-CoV-2 polymerase chain reaction (PCR) with persistently negative anti-SARS-CoV-2 serum immunoglobulin. Case: Our patient is a 74 year old male with follicular lymphoma on obinutuzumab. Past medical history includes obstructive sleep apnea, hypertension, and type 2 diabetes mellitus. He first incidentally tested positive for SARS-CoV-2 PCR but was asymptomatic. He presented to the hospital 3 weeks later for dyspnea, fevers, and cough. Computed tomography (CT) angiography of the chest was negative for pulmonary embolism but showed multifocal infiltrates and a nonocclusive thrombus in the inferior vena cava (IVC). Inflammatory markers were elevated. Patient was started on anticoagulation for his IVC thrombus. He did not require supplemental oxygen, and was discharged home after a short inpatient observation. The patient had 3 more hospitalizations over the next 30 days with acute hypoxic respiratory failure requiring supplemental oxygen. He had serial CT imaging of his chest that remained negative for pulmonary embolism but showed progressively worsening multifocal infiltrates. His inflammatory markers remained elevated (see figure 1). He tested negative for SARS-CoV-2 Immunoglobulin G (IgG) on day 27 and 36 from the initial COVID-19 diagnosis while repeat SARS-CoV-2 PCRs remained positive. Discussion: Immunocompromised patients with COVID 19 infection tend to have worse clinical outcomes. Our patient had persistently positive SARS-CoV-2 PCR and negative IgG beyond 30 days along with worsening respiratory symptoms. It is possible that the lack of IgG response may be related to the monoclonal antibody obinutuzumab against CD 20 cells. In the case of our patient, despite his persistent positivity of SARS-CoV-2 by rapid PCR test, we did not have confirmation of active infection by whole genome sequence or viral culture. However he had persistent clinical deterioration, elevated inflammatory markers, as well as worsening serial CT images suggesting a prolonged active infection. The findings in our patient may have significant implications in the isolation, management and prognosis of patients receiving immunosuppressive therapy, specifically anti CD 20 management.
1例使用奥比妥珠单抗的新型冠状病毒2019感染患者免疫球蛋白阴性
新型冠状病毒2019 (COVID-19)感染是一种全球性的大流行。临床过程变化很大。大多数患者恢复了体液和细胞介导的免疫,以抵抗再感染。以往的研究表明,严重感染的免疫功能正常的患者抗新冠病毒免疫球蛋白血清均呈阳性,而只有少数轻度感染的患者血清呈阴性。然而,免疫功能低下的患者可在严重感染的情况下保持血清阴性长达两个月,同时释放活性病毒。本病例描述了一位服用本例单抗的患者,其SARS-CoV-2聚合酶链反应(PCR)持续阳性,抗SARS-CoV-2血清免疫球蛋白持续阴性。病例:我们的患者是一名74岁男性,患有滤泡性淋巴瘤。既往病史包括阻塞性睡眠呼吸暂停、高血压和2型糖尿病。他最初偶然检测出SARS-CoV-2 PCR阳性,但无症状。3周后因呼吸困难、发烧和咳嗽入院。胸部CT血管造影显示肺栓塞阴性,但显示多灶浸润和下腔静脉(IVC)非闭塞性血栓。炎症标志物升高。病人开始使用抗凝剂治疗下腔静脉血栓。他不需要补充氧气,在短暂的住院观察后出院回家。在接下来的30天里,患者又因急性缺氧呼吸衰竭住院3次,需要补充氧气。他的胸部连续CT成像显示肺栓塞阴性,但显示逐渐恶化的多灶浸润。他的炎症标志物仍然升高(见图1)。在首次诊断COVID-19后的第27天和第36天,他的SARS-CoV-2免疫球蛋白G (IgG)检测呈阴性,而重复SARS-CoV-2 pcr检测仍呈阳性。讨论:COVID - 19感染免疫功能低下患者的临床预后往往较差。患者SARS-CoV-2 PCR持续阳性,IgG持续阴性超过30天,呼吸道症状加重。缺乏IgG应答可能与针对cd20细胞的单克隆抗体obinutuzumab有关。在我们的病例中,尽管通过快速PCR检测他的SARS-CoV-2持续呈阳性,但我们没有通过全基因组测序或病毒培养确认活动性感染。然而,他的临床症状持续恶化,炎症标志物升高,连续CT图像恶化,提示长期活动性感染。本例患者的发现可能对接受免疫抑制治疗的患者的隔离、管理和预后具有重要意义,特别是抗cd20治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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