Prevalence and characteristics of post-acute sequelae of SARS-CoV-2 (PASC) in non-hospitalized persons with COVID-19 enrolled in a clinical trial of early treatment (ACTIV-2)

Objectives/aim: Many persons with SARS-CoV-2 experience clinical symptoms beyond acute infection, often termed 'long COVID' or 'post-acute sequelae of SARS-CoV-2 infection (PASC)'. PASC studies embedded within COVID-19 therapeutics trials provide a unique opportunity to describe the incidence, symptom burden, and impact of different antiviral therapies on PASC prevalence. Methods: ACTIV-2 evaluates the safety and efficacy of investigational agents for the treatment of non-hospitalized adults with mild to moderate COVID-19 in a Phase 2/3 platform trial. In the inaugural Phase 2 portion, participants in the US were randomized within 10 days of symptom onset and a positive test for SARS-CoV-2 to receive the SARS-CoV-2 anti-spike monoclonal antibody bamlanivimab or placebo as a single infusion at 7,000 mg (n=94) or 700 mg (n=225). In a subsequent single-arm open-label study, 1059 participants received 700 mg of bamlanivimab. Participants completed a 13-symptom daily diary from enrollment through day 28. A long-term (LT) symptom diary with 14 additional symptoms was introduced after the study was underway and a subset of individuals completed these during follow-up every 12 weeks starting at week 12 on study. We report initial findings from available week 24 data. Results: 605 participants enrolled August 2020 to February 2021 completed the LT diary at their 24-week visit (Phase 2: 7000 mg versus placebo (n=25); 700 mg versus placebo (n=68); open-label cohort: 700 mg (n=512)). Median age of respondents was 50 years (quartiles: 39, 60), 51% were female, 5% Black/African American, and 35% Hispanic/Latino. At study enrollment, 53% reported at least 1 high-risk comorbidity, and 0.3% were vaccinated against COVID-19. By week 24, 14% (87/605) of respondents self-reported that they had not returned to their pre-COVID-19 health with most common symptoms in this group being fatigue and smell disorder (45% and 36%, respectively). Other symptoms included breathing difficulties (30%), taste disorders (25%), musculoskeletal pain (26%) or weakness (23%), and cognitive complaints including difficulty concentrating/thinking (30%), difficulty reasoning and solving problems (21%), memory loss (25%) and insomnia (23%). Most reported their symptoms as 'mild'. 57% (50/87) reported the presence of three or more PASC symptoms at week 24. Exploratory analyses have not shown differences in rates of reported PASC symptoms between bamlanivimab and placebo groups. Conclusion(s)/discussion