# Successful Treatment of Persistent and Relapsing COVID-19 with Ensitrelvir in a Patient with Obinutuzumab-Induced Long-Term B-Cell Depletion: A Case Report

## TL;DR

A patient with long-term B-cell depletion due to obinutuzumab treatment showed rapid improvement in persistent and relapsing COVID-19 after being treated with ensitrelvir.

## Contribution

This case report highlights ensitrelvir's effectiveness in treating persistent or refractory COVID-19 in immunocompromised patients.

## Key findings

- Ensitrelvir led to rapid decline in SARS-CoV-2 antigen levels and clinical improvement in a patient with persistent and relapsing COVID-19.
- The patient's condition did not improve with remdesivir and dexamethasone prior to ensitrelvir treatment.
- Patients treated with obinutuzumab may remain immunosuppressed for years, requiring tailored antiviral strategies.

## Abstract

Background and Clinical Significance: Ensitrelvir is an oral inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (3CL pro). Compared with remdesivir and molnupiravir, ensitrelvir achieves higher rates of SARS-CoV-2 antigen clearance and a more favorable viral shedding profile. Case Presentation: A 67-year-old Japanese man with follicular lymphoma had received obinutuzumab plus bendamustine, followed by obinutuzumab maintenance therapy. Hypogammaglobulinemia and profound B-cell depletion persisted for more than 1 year after the final maintenance dose. Three months prior to the current admission, the patient developed coronavirus disease 2019 (COVID-19) and was treated with a 10-day course of remdesivir and dexamethasone. The patient subsequently presented with recurrent COVID-19 pneumonia. Treatment with remdesivir and dexamethasone did not result in clinical improvement, and the SARS-CoV-2 antigen level increased despite adjunctive intravenous immunoglobulin. After ensitrelvir was added to remdesivir, the SARS-CoV-2 antigen levels declined rapidly, and clinical parameters, including fever, inflammatory markers (C-reactive protein), and oxygenation, improved promptly, allowing for discharge. Conclusions: Ensitrelvir may be an effective therapeutic option for the treatment of persistent or refractory COVID-19 in immunocompromised patients. Clinicians should recognize that patients treated with obinutuzumab may remain immunosuppressed for several years after therapy.