ABSTRACT
Background: We assessed the efficacy of a single dose of peginterferon lambda in preventing clinical events among acutely symptomatic COVID-19 outpatients. Method(s): We conducted a placebo-controlled, randomized, adaptive platform trial among predominantly vaccinated SARS-CoV-2-positive adults in Brazil and Canada receiving either one subcutaneous injection of peginterferon lambda or placebo. The primary composite endpoint was medical admission to hospital, defined as either observation in a COVID-19 emergency setting for > 6 hours, or transfer to a tertiary hospital due to symptomatic COVID-19 within 28 days post-randomization. Result(s): For this evaluation, 931 patients received peginterferon lambda and 1018 received placebo. 84% of the population were vaccinated and the trial occurred across multiple COVID-19 variants. In the primary analysis of patients, the primary outcome was reduced by 51% in the peginterferon lambda vs. placebo groups (relative risk 0.49 [25/916 vs 57/1003], 95% Bayesian credible interval 0.30-0.76, posterior probability >99.9%). This effect was maintained in subgroup analyses including COVID-19-related hospitalization alone (relative risk 0.57, 95% Bayesian credible intervals 0.33-0.95, ) and COVID-19-related hospitalization or death (Hazard ratio 0.59, 95% Bayesian credible interval 0.35- 0.97). The effects were consistent across dominant variants and vaccination status. Among individuals with a high viral level at baseline, peginterferon lambda resulted in lower viral loads by Day 7, compared to placebo. The incidence of adverse events was similar in the two groups. Conclusion(s): Among predominantly vaccinated outpatients with COVID-19, single-dose of peginterferon lambda resulted in significantly decreased clinical events.
ABSTRACT
Background: This study aimed to investigate the efficacy and safety of subcutaneous injection of peginterferon lambda in patients hospitalized with COVID-19. Methods: In this study (NCT04343976), patients admitted to hospital with COVID-19 confirmed by RT-PCR from nasopharyngeal swab were randomly assigned within 48 h to receive peginterferon lambda or placebo in a 1:1 ratio. Participants were subcutaneously injected with a peginterferon lambda or saline placebo at baseline and day 7 and were followed up until day 14. Results: We enrolled 14 participants; 6 participants (85.7%) in the peginterferon lambda group and 1 participant (14.3%) in the placebo group were treated with remdesivir prior to enrollment. Fifty percent of participants were SARS-CoV-2 RNA negative at baseline although they tested SARS-CoV-2 RNA positive within 48 h of randomization. Among participants who were SARS-CoV-2 positive at baseline, 2 out of 5 participants (40%) in the peginterferon lambda group became negative at day 14, while 0 out of 2 participants (0%) in the placebo group achieved negativity for SARS-CoV-2 by day 14 (p > 0.05). The median change in viral load (log copies per ml) was +1.72 (IQR -2.78 to 3.19) in the placebo group and -2.22 (IQR -3.24 to 0.55) in the peginterferon lambda group at day 14 (p = 0.24). Symptomatic changes did not differ between the two groups. Peginterferon lambda was well tolerated with a few treatment-related adverse effects. Conclusion: Peginterferon lambda appears to accelerate SARS-CoV-2 viral load decline and improve plasma disease progression markers in hospitalized patients with COVID-19.
ABSTRACT
Background. Persistent symptoms after acute COVID-19 are being increasingly reported. To date, little is known about the cause, clinical associations, and trajectory of "Long COVID". Methods. Participants of an outpatient clinical trial of Peginterferon-Lambda as treatment for uncomplicated SARS-CoV-2 infection were invited to long term follow-up visits 4, 7, and 10 months after initial COVID-19 diagnosis. Ongoing symptoms and functional impairment measures (work productivity and activity index (WPAI), NIH toolbox smell test, 6-minute walk test) were assessed and blood samples obtained. "Long COVID" was defined as presence of 2 or more typical symptoms (fatigue, hyposmia/hypogeusia, dyspnea, cough, palpitations, memory problems, joint pain) at follow up. Associations between baseline characteristics, initial COVID-19 clinical course, and presence of "Long COVID" during follow-up were assessed using generalized estimating equations accounting for repeated measurements within individuals. Results. Eighty-seven participants returned for at least one follow-up visit. At four months, 29 (34.1%) had "Long COVID";19 (24.7%) met criteria at 7 months and 18 (23.4%) at 10 months (Figure 1). Presence of "Long COVID" symptoms did not correlate significantly with functional impairment measures. Female gender (OR 3.01, 95% CI 1.37-6.61) and having gastrointestinal symptoms during acute COVID-19 illness (OR 5.37, 95% CI 1.02-28.18) were associated with "Long COVID" during follow-up (Figure 2). No significant associations with baseline immunologic signatures were observed. Conclusion. "Long COVID" was prevalent in this outpatient trial cohort and had low rates of resolution over 10 months of follow up. Female sex and gastrointestinal symptoms during acute illness were associated with "Long COVID". Identifying modifiable risk factors associated with the development of persistent symptoms following SARS-CoV-2 infection remains a critical need.