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Efficacy of late-onset antiviral treatment in immunocompromised hosts with persistent SARS-CoV-2 infection

  • 0Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta, Georgia, USA.
Journal of Virology +

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August 29, 2024

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August 29, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Late-onset direct-acting antiviral (DAA) therapy effectively reduces prolonged SARS-CoV-2 replication in immunocompromised mice. Extended treatment may be necessary for maximal benefit in vulnerable patients.

Area Of Science

  • Virology
  • Immunology
  • Pharmacology

Background

  • Immunocompromised individuals face high risks of prolonged SARS-CoV-2 infection and severe COVID-19.
  • Limited understanding exists regarding the efficacy of late-onset direct-acting antiviral (DAA) therapies for persistent viral replication in this population.

Purpose Of The Study

  • To investigate the effectiveness of late-onset DAA therapy in an immunocompromised mouse model with prolonged SARS-CoV-2 replication.
  • To compare the efficacy of nirmatrelvir/ritonavir (Paxlovid), molnupiravir, and the experimental drug 4'-fluorouridine (4'-FlU).

Main Methods

  • Developed a mouse model by depleting CD4+ and CD8+ T cells, leading to prolonged SARS-CoV-2 (beta variant) replication for 5 weeks.
  • Administered Paxlovid, molnupiravir, or 4'-FlU at late-onset (14 days post-infection) for 7 or 14 days.
  • Assessed viral load in respiratory compartments and monitored for viral rebound and resistance emergence.

Main Results

  • 4'-FlU rapidly reduced viral load 4 days post-infection; all DAAs lowered viral burden after 7 days of late-onset treatment.
  • Paxlovid-treated animals showed viral rebound post-treatment and detectable RNA at 28 days post-infection.
  • No drug-resistant SARS-CoV-2 variants emerged, but prolonged replication persisted in vehicle controls.

Conclusions

  • Late-onset DAA therapy significantly shortens the duration of persistent SARS-CoV-2 replication in immunocompromised hosts.
  • Extended treatment courses may be crucial for achieving maximal therapeutic benefit and preventing rebound.
  • Further clinical trials are warranted to optimize antiviral strategies for immunocompromised COVID-19 patients.

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