Frequent Emergence of Resistance Mutations Following Complex Intra-Host Genomic Dynamics in SARS-CoV-2 Patients Receiving Sotrovimab
Rosalía Palomino‐Cabrera, Francisco Tejerina, Andrea Molero‐Salinas, María Ferris, Cristina Veintimilla, Pilar Catalán, Gabriela Rodríguez Macias, Roberto Alonso, Patricia Muñóz, Darı́o Garcı́a de Viedma, Laura Pérez‐Lago, Luís Alcalá, Teresa Aldámiz, Roberto Alonso, Ana Álvarez‐Uría, Elena Bermúdez, Emilio Bouza, Sergio Buenestado‐Serrano, Almudena Burillo, Raquel Carrillo, Pilar Catalán, Emilia Cercenado, Alejandro Cobos, Cristina Díez, Pilar Escribano, Agustín Estévez, Chiara Fanciulli, Alicia Galar, María Dolores García García, Darı́o Garcı́a de Viedma, Paloma Gijón, Helmuth Guillén, Jesús Guinea, Marta Herránz, Álvaro Irigoyen, Martha Kestler, Juan Carlos López, Marina Machado, Mercedes Marín, Pablo Martín‐Rabadán, Andrea Molero‐Salinas, Pedro Montilla, Patricia Muñóz, Belén Padilla, Rosalía Palomino‐Cabrera, M.J. Palomo, María Jesús Pérez-Granda, Daniel Peñas-Utrilla, Laura Pérez‐Lago, Leire Pérez, Elena Reigadas, Cristina Rincón, Belén Rodríguez, Sara Rodríguez, Cristina Rodríguez‐Grande, Adriana Rojas, María Jesús Ruiz‐Serrano, Carlos Sánchez, M. Cantero Sanchez, Amadeo Sanz-Pérez, Julia Serrano, Francisco Tejerina, Maricela Valerio, Ma Cristina Veintimilla, Lara Vesperinas, Teresa Vicente, Sofía de la Villa
Abstract
] ≤ 32). Resistance mutations (in P337, E340, K356, and R346) were detected in 68% of cases; the shortest time to detection of a resistance mutation was 5 days after Sotrovimab infusion. The dynamics of resistance acquisition were highly complex, with up to 11 distinct amino acid changes in specimens from the same patient. In two patients, the mutation distribution was compartmentalized in respiratory samples from different sources. This is the first study to examine the acquisition of Sotrovimab resistance in the BA.5 lineage, enabling us to determine the lack of genomic or clinical differences between Sotrovimab resistance in BA.5 relative to that in BA.1/2. Across all Omicron lineages, the acquisition of resistance delayed SARS-CoV-2 clearance (40.67 versus 19.5 days). Close, real-time genomic surveillance of patients receiving Sotrovimab should be mandatory to facilitate early therapeutic interventions.