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Interferon-λ treatment accelerates SARS-CoV-2 clearance despite age-related delays in the induction of T cell immunity.
Santer, Deanna M; Li, Daniel; Ghosheh, Yanal; Zahoor, Muhammad Atif; Prajapati, Dhanvi; Hansen, Bettina E; Tyrrell, D Lorne J; Feld, Jordan J; Gehring, Adam J.
  • Santer DM; Department of Immunology, University of Manitoba, Winnipeg, MB, Canada. Deanna.Santer@umanitoba.ca.
  • Li D; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
  • Ghosheh Y; Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada.
  • Zahoor MA; Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada.
  • Prajapati D; Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada.
  • Hansen BE; Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.
  • Tyrrell DLJ; Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada.
  • Feld JJ; Department of Medical Microbiology & Immunology, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.
  • Gehring AJ; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Nat Commun ; 13(1): 6992, 2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2119412
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferons / COVID-19 Drug Treatment Type of study: Prognostic study / Randomized controlled trials Limits: Aged / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-34709-4

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferons / COVID-19 Drug Treatment Type of study: Prognostic study / Randomized controlled trials Limits: Aged / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-34709-4