The evaluation of risk factors for prolonged viral shedding during anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antivirals in COVID-19 patients with B-cell lymphoma treated by anti-CD20 antibody

BMC Infect Dis. 2024 Jul 22;24(1):715. doi: 10.1186/s12879-024-09631-3.

Abstract

Background: The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection.

Methods: This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression.

Results: Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10-20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19-38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding.

Conclusions: Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.

Keywords: Anti-CD20; B-cell lymphoma; Bendamustine; COVID-19; Persistent infection.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antiviral Agents* / administration & dosage
  • Antiviral Agents* / therapeutic use
  • COVID-19 Drug Treatment
  • COVID-19* / immunology
  • COVID-19* / virology
  • Female
  • Humans
  • Immunocompromised Host
  • Lymphoma, B-Cell* / drug therapy
  • Lymphoma, B-Cell* / immunology
  • Lymphoma, B-Cell* / virology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Rituximab / administration & dosage
  • Rituximab / therapeutic use
  • SARS-CoV-2* / drug effects
  • SARS-CoV-2* / immunology
  • Viral Load* / drug effects
  • Virus Shedding* / drug effects

Substances

  • Antiviral Agents
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Rituximab
  • Antibodies, Neutralizing