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Interferon-λ treatment accelerates SARS-CoV-2 clearance despite age-related delays in the induction of T cell immunity

Author

Listed:
  • Deanna M. Santer

    (University of Manitoba)

  • Daniel Li

    (University of Toronto
    University Health Network)

  • Yanal Ghosheh

    (University Health Network)

  • Muhammad Atif Zahoor

    (University Health Network)

  • Dhanvi Prajapati

    (University of Manitoba)

  • Bettina E. Hansen

    (University Health Network)

  • D. Lorne J. Tyrrell

    (University of Alberta)

  • Jordan J. Feld

    (University of Toronto
    University Health Network)

  • Adam J. Gehring

    (University of Toronto
    University Health Network)

Abstract

Interferons induced early after SARS-CoV-2 infection are crucial for shaping immunity and preventing severe COVID-19. We previously demonstrated that injection of pegylated interferon-lambda accelerated viral clearance in COVID-19 patients (NCT04354259). To determine if the viral decline is mediated by enhanced immunity, we assess in vivo responses to interferon-lambda by single cell RNA sequencing and measure SARS-CoV-2-specific T cell and antibody responses between placebo and interferon-lambda-treated patients. Here we show that interferon-lambda treatment induces interferon stimulated genes in peripheral immune cells expressing IFNLR1, including plasmacytoid dendritic cells and B cells. Interferon-lambda does not affect SARS-CoV-2-specific antibody levels or the magnitude of virus-specific T cells. However, we identify delayed T cell responses in older adults, suggesting that interferon-lambda can overcome delays in adaptive immunity to accelerate viral clearance in high-risk patients. Altogether, interferon-lambda offers an early COVID-19 treatment option for outpatients to boost innate antiviral defenses without dampening peripheral adaptive immunity.

Suggested Citation

  • Deanna M. Santer & Daniel Li & Yanal Ghosheh & Muhammad Atif Zahoor & Dhanvi Prajapati & Bettina E. Hansen & D. Lorne J. Tyrrell & Jordan J. Feld & Adam J. Gehring, 2022. "Interferon-λ treatment accelerates SARS-CoV-2 clearance despite age-related delays in the induction of T cell immunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34709-4
    DOI: 10.1038/s41467-022-34709-4
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