Early Treatment with Pegylated Interferon Lambda for Covid-19
Gilmar Reis, Eduardo A S Moreira Silva, Daniela C Medeiros Silva, Lehana Thabane, Vitoria H S Campos, Thiago S Ferreira, Castilho V Q Santos, Ana M R Nogueira, Ana P F G Almeida, Leonardo C M Savassi, Adhemar D Figueiredo-Neto, Ana C F Dias, Adelino M Freire Júnior, Carina Bitarães, Aline C Milagres, Eduardo D Callegari, Maria I C Simplicio, Luciene B Ribeiro, Rosemary Oliveira, Ofir Harari, Lindsay A Wilson, Jamie I Forrest, Hinda Ruton, Sheila Sprague, Paula Mckay, Christina M Guo, Eve H Limbrick-Oldfield, Steve Kanters, Gordon H Guyatt, Craig R Rayner, Christopher Kandel, Mia J Biondi, Robert Kozak, Bettina Hansen, M Atif Zahoor, Paul Arora, Colin Hislop, Ingrid Choong, Jordan J Feld, Edward J Mills, Jeffrey S Glenn
New England Journal of Medicine, doi:10.1056/nejmoa2209760
BACKGROUND The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear.
METHODS We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization.
RESULTS A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups.
CONCLUSIONS Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.
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'affiliation': [ { 'name': 'From ViRx@Stanford, Stanford Biosecurity and Pandemic '
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'Departments of Medicine (Division of Gastroenterology and '
'Hepatology) and Microbiology and Immunology, Stanford University '
'School of Medicine (J.S.G.), Stanford, and the Veterans Affairs '
'Medical Center (J.S.G.) and Eiger BioPharmaceuticals (C.H., '
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'Cardresearch–Cardiologia Assistencial e de Pesquisa (G.R., '
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{ 'given': 'Eve H.',
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'Medical Center (J.S.G.) and Eiger BioPharmaceuticals (C.H., '
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'Cardresearch–Cardiologia Assistencial e de Pesquisa (G.R., '
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{ 'given': 'Steve',
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'Departments of Medicine (Division of Gastroenterology and '
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'School of Medicine (J.S.G.), Stanford, and the Veterans Affairs '
'Medical Center (J.S.G.) and Eiger BioPharmaceuticals (C.H., '
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'Cardresearch–Cardiologia Assistencial e de Pesquisa (G.R., '
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{ 'given': 'Gordon H.',
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'Medical Center (J.S.G.) and Eiger BioPharmaceuticals (C.H., '
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'Cardresearch–Cardiologia Assistencial e de Pesquisa (G.R., '
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{ 'given': 'Craig R.',
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'Cardresearch–Cardiologia Assistencial e de Pesquisa (G.R., '
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'Cardresearch–Cardiologia Assistencial e de Pesquisa (G.R., '
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'Cardresearch–Cardiologia Assistencial e de Pesquisa (G.R., '
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'Cardresearch–Cardiologia Assistencial e de Pesquisa (G.R., '
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