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

Interferons (IFNs) 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-lambda1 (PEG-IFN-λ) accelerated viral clearance in COVID-19 patients. To determine if the viral decline was mediated by enhanced immunity, we assessed in vivo responses to PEG-IFN-λ by single cell RNA sequencing and measured SARS-CoV-2-specific T cell and antibody responses between placebo and PEG-IFN-λ-treated patients. PEG-IFN-λ treatment induced interferon stimulated genes in peripheral immune cells expressing IFNLR1, including plasmacytoid dendritic cells and B cells. PEG-IFN-λ did not affect SARS-CoV-2-specific antibody levels or the magnitude of virus-specific T cells. However, we identified delayed T cell responses in older adults, suggesting that PEG-IFN-λ can overcome delays in adaptive immunity to accelerate viral clearance in high-risk patients. Altogether, PEG-IFN-λ offers an early COVID-19 treatment option for outpatients to boost innate antiviral defenses without dampening peripheral adaptive immunity. PBMCs were isolated from COVID-19 patients treated with placebo or pegylated-IFN-lambda1 and analyzed by scRNA seq at 3 time points before or after treatment (n=9 subjects). Submitter declares: "Due to patient privacy concerns, we are unable to submit raw sequences."