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

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.