Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice

Viruses. 2023 Apr 19;15(4):999. doi: 10.3390/v15040999.

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.

Keywords: COVID-19; Delta variant; Gamma variant; K18-hACE2; SARS-CoV-2; variants of concern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COVID-19*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Transgenic
  • Pandemics
  • SARS-CoV-2* / genetics
  • Virulence

Substances

  • K-18 conjugate
  • ACE2 protein, human

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This work was primarily funded by grants from the São Paulo Research Foundation-FAPESP (grants nos. 2020/06747-4 to C.R.F.M.; 2020/06409-1 to ELD; 2020/03163-1 to S.E.; 2015/26722-8 to C.W.; 2019/12068-5 to J.G.D.; 2020/12277-0 to E.E.S.; 2020/04923-0 to L.R.F.; 2018/18257-1, 2018/15549-1, 2020/04923-0 to G.P.; 2020/10127-1 to D.T.C. and R.C.); The National Council for Scientific and Technological Development-CNPq (grants nos. 302917/2019-5 and 408636/2018-1 to C.R.F.M.; 304033/2021-9 to S.E.; 301524/2019-0 to C.W.; 307854/2018-3 to G.P.; 409216/2018-6 to J.G.D. and 316462/2021-7 to L.J.d.M.C.); Coordination for the Improvement of Higher Education Personnel-CAPES (grants nos. 88887.509097/2020-00 to Y.S.S., 18/15549-1 to L.R.F.); Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro-FAPERJ (grants no. E-26/200.314/2022-260923 to L.J.d.M.C.; Oswaldo Cruz Foundation Rio de Janeiro-FIOCRUZ (grants no. VPPCB-005-FIO-20-2-49 to L.J.d.M.C.).