Infection with the SARS-CoV-2 B.1.351 variant is lethal in aged BALB/c mice

Sci Rep. 2022 Mar 9;12(1):4150. doi: 10.1038/s41598-022-08104-4.

Abstract

Models of animals that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can usefully evaluate the efficacy of vaccines and therapeutics. In this study, we demonstrate that infection with the SARS-CoV-2 B.1.351 variant (TY8-612 strain) induces bodyweight loss and inflammatory cytokine/chemokine production in wild-type laboratory mice (BALB/c and C57BL/6 J mice). Furthermore, compared to their counterparts, BALB/c mice had a higher viral load in their lungs and worse symptoms. Importantly, infecting aged BALB/c mice (older than 6 months) with the TY8-612 strain elicited a massive and sustained production of multiple pro-inflammatory cytokines/chemokines and led to universal mortality. These results indicated that the SARS-CoV-2 B.1.351 variant-infected mice exhibited symptoms ranging from mild to fatal depending on their strain and age. Our data provide insights into the pathogenesis of SARS-CoV-2 and may be useful in developing prophylactics and therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • COVID-19 / mortality
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Lung / pathology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Principal Component Analysis
  • RNA, Viral / metabolism
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / physiology*
  • Severity of Illness Index
  • Viral Load

Substances

  • Chemokines
  • Cytokines
  • RNA, Viral

Supplementary concepts

  • SARS-CoV-2 variants