POST-ACUTE SEQUELAE of SARS-CoV-2 in NONHOSPITALIZED ACTIV-2 TRIAL PARTICIPANTS

ABSTRACT

Background: Randomized COVID-19 trials provide opportunities to describe post-acute sequelae of SARS-CoV-2 (PASC)-related symptom burden longitudinally and assess the impact of early use of antivirals on PASC prevalence. Methods: ACTIV-2 evaluates safety and efficacy of investigational agents for non-hospitalized adults with mild to moderate COVID-19 in a Phase II/III trial. In Phase II, participants were randomized within 10 days of symptom onset and a positive SARS-CoV-2 virologic test to receive bamlanivimab (BAM) or placebo as a single infusion at 7000mg (n=94) or 700mg (n=225). In a subsequent single-arm open-label study, 1059 participants received 700mg BAM. Participants completed a 13-symptom daily diary from enrollment through Day 28. A long-term (LT) diary (14 additional symptoms) introduced after the study was underway was completed by a subset of individuals every 12 weeks. We report Week 24 findings. Results: Between Aug 2020 to Feb 2021 605 participants enrolled and completed LT diary at Week 24 [Phase II 7000mg vs. placebo (n=25);700mg vs. placebo (n=68);single-arm open-label cohort 700mg (n=512)]. Median age was 50 years, 51% female sex, 99% identified as cis-gender, 5% Black/African American, and 35% Hispanic/Latino. At enrollment, 53% reported ≥1 high-risk comorbidity and 0.3% were vaccinated against COVID-19. By Week 24, 14% (87/605) had not returned to their pre-COVID-19 health by self-report, with 57% (50/87) reporting ≥3 PASC symptoms. The most common symptoms were fatigue (45% of 87), smell disorder (36%), breathing difficulties (30%), taste disorders (25%), musculoskeletal pain (26%) or weakness (23%), and cognitive complaints difficulty concentrating/thinking (30%), difficulty reasoning and solving problems (21%), memory loss (25%) and insomnia (23%). Most reported symptoms as "mild". Participants who reported acute viral illness symptoms between Days 22-28 were more likely to report PASC symptoms at Week 24 than those who did not report symptoms at Days 22-28 [51% (164/320) vs. 27% (76/285);p<0.0001]. Conclusion: In outpatients with mild to moderate COVID-19, 14% had not returned to pre-COVID-19 health by 24 weeks post infection, with generally mild but multiple symptoms. Presence of acute viral illness symptoms at 3-4 weeks was associated with an increased risk of PASC symptoms months later. Larger placebo-controlled studies within ACTIV-2 will assess the potential for early antiviral therapies to mitigate or prevent PASC.