1. Post-acute COVID-19 outcomes including participant-reported long COVID: amubarvimab/romlusevimab versus placebo in the ACTIV-2 trial
- Author
-
Evering, Teresa H, Moser, Carlee, Jilg, Nikolaus, Ritz, Justin, Wohl, David A, Li, Jonathan Z, Margolis, David, Javan, Arzhang Cyrus, Eron, Joseph J, Currier, Judith S, Daar, Eric S, Smith, Davey M, Hughes, Michael D, Chew, Kara W, Chew, Kara, Smith, David, Daar, Eric, Wohl, David, Currier, Judith, Eron, Joseph, Hughes, Michael, Giganti, Mark, Hosey, Lara, Roa, Jhoanna, Patel, Nilam, Colsh, Kelly, Rwakazina, Irene, Beck, Justine, Sieg, Scott, Li, Jonathan, Fletcher, Courtney, Fischer, William, Ignacio, Rachel Bender, Cardoso, Sandra, Corado, Katya, Jagannathan, Prasanna, Perelson, Alan, Pillay, Sandy, Riviere, Cynthia, Singh, Upinder, Taiwo, Babafemi, Gottesman, Joan, Newell, Matthew, Pedersen, Susan, Dragavon, Joan, Jennings, Cheryl, Greenfelder, Brian, Murtaugh, William, Kosmyna, Jan, Gapara, Morgan, Shahkolahi, Akbar, Lacal, Verónica, Salusso, Diego, Nuñez, Sebastian, Rodriguez, Marcelo Rodrigo, Laborde, Luciana, Papasidero, Marcelo, Wehbe, Luis, Gonzalez, Mariana, Voena, Felicitas Fernandez, Alvarez, Tomas, Lopez, Amaru, Huhn, Virginia, Nores, Ulises D'Andrea, Dieser, Pablo, Bordese, Fernando, Mussi, Marisa, de Carvalho Santana, Rodrigo, Bárbaro, Adriana Aparecida Tiraboschi, Santos, Breno, de Cássia Alves Lira, Rita, da Silva, Andre Luiz Machado, Cardoso, Sandra Wagner, Ribeiro, Maria Pia Diniz, Soliva, Nathália, Vasconcellos, Eduardo, Ribeiro, Jorge Eurico, Enéas, Miriam Amaral, Pinto, Jorge, de Morais Caporali, Julia Fonseca, Ferreira, Flávia Gomes Faleiro, Martinez, Norma Erendira Rivera, Lopez, Victor Casildo Bohorquez, Frias, Melchor Victor, Fetalvero, Krystle, Maranan, Alyxzza, Rosa, Jennifer, Coetzer, Thomas, Mohata, Maureen, Lalloo, Umesh, Madlala, Penelope, Pillay-Ramaya, Larisha, and Bennet, Jaclyn Ann
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Coronaviruses ,Clinical Research ,Emerging Infectious Diseases ,Prevention ,6.1 Pharmaceuticals ,Good Health and Well Being ,COVID-19 ,Monoclonal antibodies ,Outpatient treatment ,Clinical trial ,Post COVID conditions ,Long COVID ,Post-acute sequelae of SARS-CoV-2 infection ,ACTIV-2/A5401 Study Team ,Clinical sciences ,Health services and systems ,Public health - Abstract
BackgroundIt is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID.MethodsNon-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo.FindingsParticipants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID.InterpretationAmubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID.FundingNational Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.
- Published
- 2024