Effectiveness of early-treatment interventions on self-reported long COVID: A multi-arm, multi-stage adaptive platform control trial

Approximately 20% of people infected with COVID-19 develop at least one persistent condition potentially attributable to their SARS-CoV-2 infection. We sought to determine the effectiveness of early COVID-19 treatment interventions on long COVID symptoms. We conducted a multi-arm multi-stage adaptive platform trial at 12 public health clinics in Brazil between June 2020 and July 2022. Participants were followed for 60. Patients received one of six interventions (doxazosin, fluvoxamine, fluvoxamine in combination with inhaled budesonide, interferon-lambda, ivermectin, or metformin) or matching placebo. The primary outcome was persistence of COVID-19 symptoms at 60 days after randomization. We analyzed data from 5,700 participants across study cohorts. Overall, approximately 22% of patients reported at least one ongoing symptom 60 days after randomization, regardless of the early treatment they received. At day 60, we did not find any statistical benefit of any intervention on recovery, cure fractions, or PROMIS scores (mental and physical).