SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice

Abstract

The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern pose a major threat to public health, due to possible enhanced virulence, transmissibility and immune escape. These variants may also adapt to new hosts, in part through mutations in the spike protein. In this study, we evaluated the infectivity and pathogenicity of SARS-CoV-2 variants of concern in wild-type C57BL/6 mice. Six-week-old mice were inoculated intranasally with a representative virus from the original B.1 lineage, or the emerging B.1.1.7 and B.1.351 lineages. We also infected a group of mice with a mouse-adapted SARS-CoV-2 (MA10). Viral load and mRNA levels of multiple cytokines and chemokines were analyzed in the lung tissues on day 3 after infection. Our data show that unlike the B.1 virus, the B.1.1.7 and B.1.351 viruses are capable of infecting C57BL/6 mice and replicating at high concentrations in the lungs. The B.1.351 virus replicated to higher titers in the lungs compared with the B.1.1.7 and MA10 viruses. The levels of cytokines (IL-6, TNF-α, IL-1β) and chemokine (CCL2) were upregulated in response to the B.1.1.7 and B.1.351 infection in the lungs. In addition, robust expression of viral nucleocapsid protein and histopathological changes were detected in the lungs of B.1.351-infected mice. Overall, these data indicate a greater potential for infectivity and adaptation to new hosts by emerging SARS-CoV-2 variants.

Omicron: What Makes the Latest SARS-CoV-2 Variant of Concern So Concerning?

“…Coronaviruses are notorious for their ability to cross species barriers, and recent findings suggest that SARS-CoV-2 can be detected, e.g., in household pets and farm and captive animals as well as wildlife ( 42 ). It has been suggested that SARS-CoV-2 VOCs show an expanded host range and thus possess an increased capacity to generate new animal reservoirs ( 43 , 44 ). However, the fact that a significant portion of changes in the Omicron genome is identical to human-specific adaptations found in other VOCs and the preliminary evidence for high replication and transmission fitness suggest emergence in humans.…”

SARS-CoV-2 Infects Primary Neurons from Human ACE2 Expressing Mice and Upregulates Genes Involved in the Inflammatory and Necroptotic Pathways

“…The cDNA was synthesized from RNA using an iScript™ cDNA Synthesis Kit (Bio-Rad). The qRT-PCR was used to determine the expression levels of multiple host genes [51]. The fold-change in infected samples compared to control samples was calculated after normalizing to the housekeeping GAPDH gene [28,45,47,48].…”

Long term detection and quantification of SARS-CoV-2 RNA in wastewater in Bahrain

“…Additionally, it is also possible that increases of SARS-CoV-2 in wastewater could be associated to wild animal discharges into the wastewater system. Recently, it has been shown that SARS-CoV-2 variants can infect mice, meaning their discharges should be taken into consideration when analysing levels of the viral genes in wastewater ( Pan et al 2021 , Stone et al 2021 ). However, it is worth noting that whilst this is possible, wild animals have not been observed in the Muharraq Wastewater Services Company's sewers since they were brought into service in 2014.…”