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

Deanna M. Santer (), Daniel Li, Yanal Ghosheh, Muhammad Atif Zahoor, Dhanvi Prajapati, Bettina E. Hansen, D. Lorne J. Tyrrell, Jordan J. Feld and Adam J. Gehring ()
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Deanna M. Santer: University of Manitoba
Daniel Li: University of Toronto
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
Adam J. Gehring: University of Toronto

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34709-4

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