Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice
Yasmin da Silva Santos,
Thais Helena Martins Gamon,
Marcela Santiago Pacheco de Azevedo,
Bruna Larotonda Telezynski,
Edmarcia Elisa de Souza,
Danielle Bruna Leal de Oliveira,
Jamille Gregório Dombrowski,
Livia Rosa-Fernandes,
Giuseppe Palmisano,
Leonardo José de Moura Carvalho,
Maria Cecília Rui Luvizotto,
Carsten Wrenger,
Dimas Tadeu Covas,
Rui Curi,
Claudio Romero Farias Marinho,
Edison Luiz Durigon,
Sabrina Epiphanio
Affiliations
Yasmin da Silva Santos
Laboratory of Cellular and Molecular Immunopathology of Malaria, Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Thais Helena Martins Gamon
Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Marcela Santiago Pacheco de Azevedo
Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Bruna Larotonda Telezynski
Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Edmarcia Elisa de Souza
Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Danielle Bruna Leal de Oliveira
Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Jamille Gregório Dombrowski
Laboratory of Experimental Immunoparasitology, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Livia Rosa-Fernandes
Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Giuseppe Palmisano
GlycoProteomics Laboratory, Department of Parasitology, ICB, University of São Paulo, São Paulo 05508-000, Brazil
Leonardo José de Moura Carvalho
Laboratory of Malaria Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil
Maria Cecília Rui Luvizotto
School of Veterinary Medicine of Araçatuba, São Paulo State University, São Paulo 16050-680, Brazil
Carsten Wrenger
Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Dimas Tadeu Covas
Butantan Institute, São Paulo 05508-040, Brazil
Rui Curi
Interdisciplinary Program of Health Sciences, Cruzeiro do Sul University, São Paulo 08060-070, Brazil
Claudio Romero Farias Marinho
Laboratory of Experimental Immunoparasitology, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Edison Luiz Durigon
Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Sabrina Epiphanio
Laboratory of Cellular and Molecular Immunopathology of Malaria, Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
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.
