Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice
Yasmin da Silva Santos, Thaís Helena Martins Gamon, Marcela de Azevedo, Bruna Larotonda Telezynski, Edmárcia Elisa de Souza, Danielle Bruna Leal Oliveira, Jamille Gregório Dombrowski, Lívia Rosa-Fernandes, Giuseppe Palmisano, Leonardo José de Moura Carvalho, Maria Cecília Rui Luvizotto, Carsten Wrenger, Dimas Tadeu Covas, Rui Curi, Cláudio Romero Farias Marinho, Edison Luíz Durigon, Sabrina Epiphânio
Abstract
Since December 2019, the world has been experiencing the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we now face the emergence of several variants. We aimed to assess the differences between the wild-type (Wt) (Wuhan) strain and the P.1 (Gamma) and Delta variants using infected K18-hACE2 mice. The clinical manifestations, behavior, virus load, pulmonary capacity, and histopathological alterations were analyzed. The P.1-infected mice showed weight loss and more severe clinical manifestations of COVID-19 than the Wt and Delta-infected mice. The respiratory capacity was reduced in the P.1-infected mice compared to the other groups. Pulmonary histological findings demonstrated that a more aggressive disease was generated by the P.1 and Delta variants compared to the Wt strain of the virus. The quantification of the SARS-CoV-2 viral copies varied greatly among the infected mice although it was higher in P.1-infected mice on the day of death. Our data revealed that K18-hACE2 mice infected with the P.1 variant develop a more severe infectious disease than those infected with the other variants, despite the significant heterogeneity among the mice.