Article
Author: Berjon Sanchez, Ruben ; Picazo Navarro, Ruben ; Bastos, Rubén ; Rodríguez Pérez, Ana Belén ; Mitjà, Oriol ; Garcia Corrochano, Cristobal ; Gómez Hijosa, Verónica ; Kaczmarczyk, Raul ; Rodríguez Barroso, Patricia ; Berriochoa Martínez de Pisón, Ma Cristina ; Navarro Sanz, Daniel ; Perez Mayoral, Cristina ; Tang, Yonggiang ; Escribano Valenciano, Irene ; Bagán-Trejo, Andrea ; García García, Isabel ; Ginés, Paz Lozano ; Bassat, Quique ; Costes, Gèlia ; Mira-Centelles, Helena ; Zalve-Cano, Ángel ; Arcarons, Anna Forcada ; Corbacho-Monné, Marc ; Gonzalez Perez, Claudia ; Escudero Planas, Adrián ; Guerrero, Elena Dorrego ; Bonilla Penedo, Celia ; Ruiz Álvarez, Patricia ; Cuevas Valiente, Laura ; Riel, Ricard ; Ramet Meseguer, Debora ; Pujol-Corney, Judit ; Finelli, Nadia ; Muñoz Castillo, David ; Ortega Martin, Ignacio ; Palau-Morral, Mariona ; Torres, Mireia ; Rodríguez-Gilabert, Carolina ; Leivas-Gutierrez, Iker ; Curto-Vicente, Verónica ; Rodriguez-Arias, Miquel Àngel ; Avila, Sara ; Muñoz Álvaro, Laura ; Díaz Urbina, Marta ; Villahoz Martín, Ainhoa ; Puigros, Laura ; Martin Poyatos, Beatriz ; Ubals, Maria ; Montes Trinidad, Rosario Paloma ; González Velayos, Maria Luz ; Donato, Carlos ; Roldan Ruiz, Alberto ; Suñer, Clara ; García-Martínez, Beatriz ; Perez Costa, Eduardo ; Rojas-Bertier, Naiara ; Galindo-Tomás, Claudia ; Nicolás Campoy, María Luisa ; Gil García, María del Rosario ; Rodrigo Testillano, Belén ; Torres Weber, Sofía ; Alonso-Vallés, Alejandro ; Ribot-Rodríguez, Rosa ; Costafreda-Hernández, Lucía ; García Lucas, Juan Antonio ; Cahís, Jordi ; Gallardo Álvarez, Daniel ; López, Patricia Morales ; Fernández Juan, Andrés ; Mondou, Elsa ; González-Beiras, Camila ; Montserrat-Lloan, Isabel ; Clotet, Bonaventura ; Gil-Fibla, Miquel ; Carrera, Caty ; Sanz, Ana ; Campins, Neus ; Gonzalez Sanchez, Maria Josefa ; Rodrigo de Vivar Azcarate, Miguel ; Blanco-Montes, Cristina ; Viader Castro, Bárbara ; Jorge, Ariadna ; González-Alonso, Raquel ; Lopez Ruiz, Cristina ; Hijós-Rullo, Mònica ; Baelo, Aida ; Galván, Antonio Valero ; Bou, Alberto Alum ; Herrero-Vila, Elisabeth ; Daimiel-Pedrote, Verónica ; Blanco Blasco, Maria ; López Rubio, Miriam ; Chen-Ye, Ana ; Del Cura-González, María Isabel ; Garcia-Cano, Laia ; Mendoza Cediel, Pablo ; Jane Chu-Sifuentes, Mary ; Vall-Mayans, Martí ; Diestro, Alicia Santos ; Reyes-Calderón, Nataly ; Hontecillas Martínez, Rodrigo ; Encabo Lopez, Susana ; Lleonart-Abadia, Montserrat ; Gil Jorge, Maria ; Prat, Núria ; Leiva-Mora, Nuria ; Espinoza Pérez, Yuri ; Guilloto López, Maria Alicia ; Buscà, Oriol ; Santamaria, Alex ; López Pérez, Blanca ; Tirado Bejarano, Fernando ; García de Villasladad Peñaranda, Miguel ; Muñoz-Burguillo, Sandra ; Mihaela Fer, Felicia ; Salmerón Martínez, Rafa ; Funollet, Blanca ; Cristina Piciorang, Lavinia ; Maqueda, Mario Oliva ; Blasco, Martí ; CristinaBerriochoa Martínez de Pisón, María ; Lupu-Yakovleva, Cristina ; Batres, Carlos ; Hueso-Mor, Alejandro ; Tejera Bodas, Alberto ; Castillo Montoya, Virginia Ivette ; Rojas Powel, Esmeralda ; Vega Ruiz, Laura ; Moreno Calvo, Maria Concepción ; Arnay Arrogante, Ruben ; Santana Briongos, Alberto ; Formentí-Pallarés, Miquel ; Moreno López, Alberto ; Cereceda Meca, Marta ; Pareja Leal, Azahara Maria ; Vera-Jurado, Edna Margarita ; Peral Bolaños, Cristina ; Israel-Benchaya, Samuel Dan ; Gozalo, Verónica ; Prats-Domenech, Ferran ; Ardila-Mejia, Gabriela ; Ara, Jordi ; Nuñez Sánchez, Sergio ; Labrador-Galván, Miguel Ángel ; Muñoz Gomez, Irene ; Fernandez Beato, Barbara ; Galvan-Casas, Cristina ; Barrientos, Ricardo Rodríguez ; Rodríguez-Salvador, Sandra ; Vazquez Ángeles, Fernanda ; Merino-Rodríguez, Carmen ; Rodríguez Andrés, Laura ; Moliner Prada, Ma Carmen ; Mencía Hernanz, Blanca ; Palomar Casado, Elena ; Sallas, Valentí ; Lopez Perez, Eva ; Botello Ariza, Raquel ; Borràs Martí, Ferran ; De-Paúl, Lucía ; Pintos-Morell, Guillem ; Díaz Rodríguez, Laura ; Paez Herrera, Enriqueta ; Recuero Renales, Mirian ; Gómez Arquero, Gema ; Flores Mateo, Gemma ; Tomillo-Martín, Olga ; Zori, Mario Mejías ; Iglesias Gonzalez, Miguel ; Medina Mateos, Elena ; Naveira Menchen, Barbara ; Juanes Perez, Miriam ; Ramos-Blanes, Rafel ; Nadal, Nuria ; Bris Rodriguez, Pilar ; Torres Martínez, Juana ; Egidos-Plaja, Antonio ; Casado Gomez, Christian ; Ojeda-Ciurana, Carmen ; Revuelta-Álvarez, Almudena ; Cejas López, Joselvis Virginia ; Torices Rasines, Teresa ; Hernanz Sotoca, Miguel ; Martínez-Alamillo, Pilar ; Dueñas Román, María Inmaculada ; Rodríguez de Torres de Paul, Jacobo ; Zurita Castrosin, Nerea Nuria ; Blázquez Valerón, Ana ; Cortijo Caballero, María ; Bustillos-Sebastian, Eilen Junet ; Vara de Rey, Patricia Jimenez ; Fraile Torres, Arturo ; Boluda, Alex ; Ortega de Felipe, Ana ; Aragón Gaspar, Elisa Rebeca ; Figueroa Caballero, Liliana ; Esteve-Tugues, Mireia ; Perez Plata, Lara Sonsoles ; Gurí, Júlia ; Nuñez Garcia, Carmen ; Vaquero Mena, Raquel ; Barnadas Vintró, Rita ; Belghazi, Omar ; Aguilar-Uroz, Adrià ; Labella Martín, Julio ; Muñoz-Martinez, Jordi ; Ouchi, Dan ; Alemany, Andrea ; Gamboa, Itziar ; Ferrerfàbrega-Costals, Lluna ; Macedo, Pablo ; Martín Molinero, Samuel ; Casado Larrañaga, Nerea ; VerónicaPlazas, Martha ; Vall-Ribalta, Esther ; Álvarez-Nieto, Noélia ; Bermejo, Jorge Iglesias ; Corral Gayubas, Sara ; Escudero, Leticia ; Tristán Morgalo, Ana Laura ; Sanz Barrio, David ; Rosell-García-Ufano, Adrià ; Fornes, Cristina ; Canudas, Josep ; Robres Medialdea, Esther ; Gordillo, Maria ; Fernández-Allende, Ana Luisa ; González Fernández-Medina, Luis ; Martínez-Pino, Juan Carlos ; Astola Requena, Ignacio ; Fletes-Pérez, Alejandro ; González Jiménez, Judith ; Balague, Lluis Esteve ; Caño de la Cruz, Mario ; Moreno Moreno, Álvaro ; Ortega, Irina ; Martín-Muñoz, Marta ; Mateo-Martínez, Anna ; Escobar-Sánchez, Rosa ; Barrios López, Vicente ; Salvador-González, Betlem ; Martínez Quintana, Rubén ; Vidal-Alaball, Josep ; Blanco Tejedor, Belen ; Millat-Martinez, Pere
BackgroundAnti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection.MethodsWe did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141.Findings461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported.InterpretationOur findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19.FundingGrifols.