Article
Author: Manne, Jennifer ; Hughes, Leslie ; Snyman, Elizma ; Daar, Eric S. ; Jagannathan, Prasanna ; Rwakazina, Irene ; Ordway, Joshua J. ; Guillory, Clinton ; Harber, Heather ; Weston, Patrick ; Juneja, Elizabeth ; Loftis, Amy James ; Weinstein, Debra ; Roman, Eloy ; Socorro, Ezequiel ; Hoover, Keila ; Surber, Joseph ; Pérez, Yadilys ; Evering, Teresa H. ; Kompelien, Breanna ; Dentoni-Lasofsky, Dennis ; Fayssoux, Jamraus ; Lalloo, Umesh ; Hazard-Jenkins, Hannah ; McHarry, Kirsten ; Chew, Kara W. ; Madlala, Penelope ; Lynch, Joshua ; Lewinski, Mary ; Pillay-Ramaya, Larisha ; Becker, Becky ; Maranan, Alyxzza ; van der Walt, Eugene ; Cheekati, Purna ; Mahmoudi, Saniyyah ; Williams-Leber, Erin ; Yawetz, Sigal ; Benson, Constance ; Smith, David (Davey) ; Huhn, Virginia ; Beck, Kelly ; Hoover, Susan E. ; Ribeiro, Jorge Eurico ; Pulliam, Sallie D. ; Gonzalez, Ana I. ; Hussen, Nazreen Jeewa ; McEvoy, Kathryn ; Hatlen, Timothy ; Amaya, Jorge P. ; Sullivano, Jennifer ; Letlape, Oteng ; Rivera Martinez, Norma Erendira ; Corado, Katya ; Lopez, Amaru ; Gomez-Martinez, Marissa ; Laborde, Luciana ; Presti, Rachel ; Coetzer, Thomas ; Bennet, Jaclyn Ann ; Cantu, Luis ; Shea, Katrina ; Varughese, Renoj ; Shaik, Sadia ; Hosey, Lara ; Mendez, Luis M. ; Focil, Augusto ; Senthil, Smruthi ; Arar, Celine ; Nakatani, Lisa ; Just, Jessica ; Zwane, Zinhle ; Berardi, Jonathan ; Maldonado, Valarie ; Hughes, Michael D. ; Rodriguez, Marcelo Rodrigo ; Jonkane, Olebogeng ; Singh, Upinder ; Smith, Davey M. ; Soliva, Nathália ; Hall, Chase ; Malla, Midhun ; Fernández, Heriberto ; Call, Robert ; Newell, Matthew ; Sieg, Scott ; Giganti, Mark ; Weston, Khalilah ; Nikolov, Boris ; Cardoso, Sandra Wagner ; Taiwo, Babafemi ; Voena, Felicitas Fernandez ; Haddad, Fadi ; Sebe, Modulakgotla ; Rolle, Charlotte-Paige ; Nuñez, Sebastian ; Gandhi, Rajesh ; Fichtenbaum, Carl ; D'Andrea Nores, Ulises ; Enéas, Miriam Amaral ; Clemency, Brian ; Vahed, Yacoob ; Fernandez, Idania ; Okeke, Nwora Lance ; Betancourt-Garcia, Monica ; Folkens, Eric ; Hendrickx, Steven ; Li, Jonathan Z. ; Leon, Ramon ; Jain, Manish ; Eron, Joseph J. ; Bordese, Fernando ; Cardoso, Sandra ; Swiatek, Joan ; Westerman, Jan ; Arnold, Melanie ; Mohata, Maureen ; Fortier, Samantha ; Lawrance Masilela, Mduduzi Sandile ; Kim, Andrew ; Petrick, Frederick ; Wohl, David ; Izquierdo, Myriam ; Sherer, Donna ; Coyne, Christopher ; Singh, Usha ; Colsh, Kelly ; Gonzalez, Noemi ; Gotur, Deepa ; Kosmyna, Jan ; Slandzicki, Jamie Alex ; Wohl, David A. ; Shahkolahi, Akbar ; Fletcher, Courtney ; Rosas, Griselda ; Herman, Jack ; Aswad, Ahmad ; Dieser, Pablo ; Mbhele, Nokuphiwa ; Ruiz, Aniuska ; Malvestutto, Carlos ; Wallan, Jessica ; Cicarella, Robyn ; Berzins, Baiba ; Day, Donald C. ; Rojas, Yaneicy Gonzalez ; Osiyemi, Olayemi ; Beck, Justine ; Jilg, Nikolaus ; Fischer, William ; Zopo, Alex ; Chew, Kara ; Neytman, Gene ; Rodriguez, Gabriel ; de Carvalho Santana, Rodrigo ; Cheekati, Vasundhara ; Joseph, Natasha ; Hernández, Maureen ; Manentsa, Mmatsie ; Hernandez, Manuel ; Johnson, Misty ; Li, Jonathan ; Free, Almena L. ; Cronin, Alexandrea ; Mbali, Rose ; Moser, Carlee ; Mehta, Sanjay ; Eziri, Emeka ; Suarez, Rosa M. ; Jennings, Cheryl ; Baer, Jenifer ; Taiwo, Babafemi O. ; Pathak, Divya ; Bukhman, Yevgeniy ; Ritz, Justin ; McGuffin, Sarah ; Machado da Silva, Andre Luiz ; Chow, Christopher ; Luetkemeyer, Anne ; Spikes, Leslie ; Farah, Humam ; Perelson, Alan ; Hughes, Michael ; Tebas, Pablo ; Pixler, April ; Torna, Odelsey ; Eron, Joseph ; Hawkins, Claudia ; Pfeffer, Michael M. ; Bohorquez Lopez, Victor Casildo ; Ignacio, Rachel Bender ; Quinn, Randall ; Keenan, Cheryl ; Riaz, Amna ; Pedersen, Susan ; Mohapi, Lerato ; Daar, Eric ; Jagizarov, Zarema ; Margolis, David ; Khan, Saahir ; Heffner, Megan ; Frias, Melchor Victor ; Mwelase, Noluthando ; Gelman, Michael ; Caloura, Matthew ; Santos, Breno ; Jonsson, Chris ; Papasidero, Marcelo ; Karpf, Cinzia ; Veltman, Jennifer ; Pullman, John ; Azizad, Masoud ; Milstone, Aaron ; Easley, Raymond ; Sein, Ni Ni ; Monlux, George W. ; Haile, Alem ; Vasconcellos, Eduardo ; Herpel, Laura Bogan ; Moyano, Susana ; Murtaugh, William ; Andriunas, Olga ; Ramirez, Rosemarie ; Atriss, Hisham ; Lummus, Christie ; Pinto, Jorge ; Moonsamy, Suri ; Rosa, Jennifer ; Wernick, Arthur ; Gottesman, Joan ; Gapara, Morgan ; Roa, Jhoanna ; Alvarez, Tomas ; Kingsley, Jeffrey ; Jain, Mamta K. ; Dragavon, Joan ; Taylor, David ; de Cássia Alves Lira, Rita ; Salusso, Diego ; Short, William ; Tripathi, Kaushlendra K. ; Currier, Judith S. ; Wilkin, Aimee ; Mussi, Marisa ; Mocherla, Bharat ; Bukhman, Eugene ; Gonzalez, Mariana ; Wehbe, Luis ; Mitha, Ismail ; Ruiz, Karelia ; Pillay, Sandy ; Kao, Wei-Hsin ; Innes, James Craig ; Lennox, Pieter ; Greenfelder, Brian ; Malik, Anju ; Fonseca de Morais Caporali, Julia ; Adonis, Tania ; Oakes, Jonathan ; Joubert, Leonard ; Dube, Michael P. ; Pham, David N. ; Dooley, Kelly ; Trentman, Sarah ; Rathore, Mobeen ; Socorro, Estefania ; McClain, Rebekah ; Avery, Ann ; DeJesus, Edwin ; Herman, Craig ; Vergara, Fernando Gonzalez ; Wilkins, Adaliah ; Davis, David ; Lacal, Verónica ; Faleiro Ferreira, Flávia Gomes ; Khodabakhshian, Aleen ; Tiraboschi Bárbaro, Adriana Aparecida ; Lutz, Allison ; Patel, Nilam ; Vaughan, Leroy ; Fetalvero, Krystle ; Hendler, Suzanne ; Pérez, Jose ; Javan, Arzhang Cyrus ; Brumskine, William ; Chiperera, Tendai ; Andrews, Nancy ; Seagle, Hannah ; Planchon, Matthew ; Williamson, Derrick ; Nagpal, Avish ; Choudhary, Madhu ; Bryan, Anna ; Dominguez, Miriam Batule ; Aziz, Mariam ; Hecker, Michelle ; Riviere, Cynthia ; Victoria, Yanly B. ; Haddad, Victoria ; Currier, Judith ; Castro, Mario ; Diniz Ribeiro, Maria Pia ; Idarraga, Samuel ; Burns, Charles M. ; Turner-Gray, Kimberly
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.