AUTHOR=Tarrés-Freixas Ferran , Trinité Benjamin , Pons-Grífols Anna , Romero-Durana Miguel , Riveira-Muñoz Eva , Ávila-Nieto Carlos , Pérez Mónica , Garcia-Vidal Edurne , Perez-Zsolt Daniel , Muñoz-Basagoiti Jordana , Raïch-Regué Dàlia , Izquierdo-Useros Nuria , Andrés Cristina , Antón Andrés , Pumarola Tomàs , Blanco Ignacio , Noguera-Julián Marc , Guallar Victor , Lepore Rosalba , Valencia Alfonso , Urrea Victor , Vergara-Alert Júlia , Clotet Bonaventura , Ballana Ester , Carrillo Jorge , Segalés Joaquim , Blanco Julià TITLE=Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice JOURNAL=Frontiers in Microbiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.840757 DOI=10.3389/fmicb.2022.840757 ISSN=1664-302X ABSTRACT=

The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2.