SARS-CoV-2 Variant Pathogenesis Following Primary Infection and Reinfection in Syrian Hamsters

Plunkard, Jessica; Mulka, Kathleen; Zhou, Ruifeng; Tarwater, Patrick M.; Zhong, William; Lowman, Margaret; Wong, Amanda; Pekosz, Andrew; Villano, Jason

doi:10.1128/mbio.00078-23

Cited by 6 publications

(6 citation statements)

References 70 publications

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“…The body weight measurement at different time points showed a body weight loss of up to 5% in both sexes of the animals up to 4 dpi followed by a gain in body weight. Previous studies have shown that the SARS-CoV-2 infection in hamsters is associated with clinical manifestations such as reduced body weight up to 7 dpi followed by recovery [19,26,27]. Further, it has been observed that the change in body weight in hamsters is associated with virus inoculum dose rather than the age of the animal [28,29].…”

Section: Discussionmentioning

confidence: 99%

Genomic Mutations in SARS-CoV-2 Genome following Infection in Syrian Golden Hamster and Associated Lung Pathologies

Rudramurthy,

Naveenkumar,

Bharathkumar

et al. 2023

Pathogens

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The continuous evolution of the SARS-CoV-2 virus led to constant developments and efforts in understanding the significance and impacts of SARS-CoV-2 variants on human health. Our study aimed to determine the accumulation of genetic mutations and associated lung pathologies in male and female hamsters infected with the ancestral Wuhan strain of SARS-CoV-2. The present study showed no significant difference in the viral load between male and female hamsters and peak infection was found to be on day four post infection in both sexes of the animals. Live virus particles were detected up to 5 days post infection (dpi) through the TCID-50 assay, while qRT-PCR could detect viral RNA up to 14 dpi from all the infected animals. Further, the determination of the neutralizing antibody titer showed the onset of the humoral immune response as early as 4 dpi in both sexes against SARS-CoV-2, and a significant cross-protection against the delta variant of SARS-CoV-2 was observed. Histopathology showed edema, inflammation, inflammatory cell infiltration, necrosis, and degeneration of alveolar and bronchial epithelium cells from 3 dpi to 14 dpi in both sexes. Furthermore, next-generation sequencing (NGS) showed up to 10 single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 (ancestral Wuhan strain) genome isolated from both male and female hamsters. The mutation observed at the 23014 position (Glu484Asp) in the SARS-CoV-2 genome isolated from both sexes of the hamsters plays a significant role in the antiviral efficacy of small molecules, vaccines, and the Mabs-targeting S protein. The present study shows that either of the genders can be used in the pre-clinical efficacy of antiviral agents against SARS-CoV-2 in hamsters. However, considering the major mutation in the S protein, the understanding of the genetic mutation in SARS-CoV-2 after passing through hamsters is crucial in deciding the efficacy of the antiviral agents targeting the S protein. Importance: Our study findings indicate the accumulation of genomic mutations in SARS-CoV-2 after passing through the Syrian golden hamsters. Understanding the genomic mutations showed that either of the hamster genders can be used in the pre-clinical efficacy of antiviral agents and vaccines.

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Section: Discussionmentioning

confidence: 99%

Genomic Mutations in SARS-CoV-2 Genome following Infection in Syrian Golden Hamster and Associated Lung Pathologies

Rudramurthy,

Naveenkumar,

Bharathkumar

et al. 2023

Pathogens

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“…The Syrian golden hamster has become the preclinical animal model of choice to assess vaccine effectiveness against SARS-CoV-2 variants, as well as the likelihood of reinfections ( 16 , 21 – 28 ). Such information is critical for rational decisions around vaccine strain updates or other public health responses to the continuing emergence of new variants.…”

Section: Discussionmentioning

confidence: 99%

“…Ryan et al saw BA.1 reinfections of hamsters infected 50 d earlier with first-wave virus but puzzlingly also recorded reinfection with homologous virus at that time interval ( 26 ). Similarly, Plunkard et al readily reinfected hamsters with BA.1 following first infections with a variety of different variants of concern ( 28 ). However they did not record virology outputs in their study but used weight loss as an indicator of infection making comparisons difficult.…”

Section: Discussionmentioning

confidence: 99%

Omicron breakthrough infections in vaccinated or previously infected hamsters

Zhou,

Sukhova,

Peacock

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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The ongoing SARS-CoV-2 epidemic was marked by the repeated emergence and replacement of “variants” with genetic and phenotypic distance from the ancestral strains, the most recent examples being viruses of the Omicron lineage. Here, we describe a hamster direct contact exposure challenge model to assess protection against reinfection conferred by either vaccination or prior infection. We found that two doses of self-amplifying RNA vaccine based on the ancestral Spike ameliorated weight loss following Delta infection and decreased viral loads but had minimal effect on Omicron BA.1 infection. Prior vaccination followed by Delta or BA.1 breakthrough infections led to a high degree of cross-reactivity to all tested variants, suggesting that repeated exposure to antigenically distinct Spikes, via infection and/or vaccination drives a cross-reactive immune response. Prior infection with ancestral or Alpha variant was partially protective against BA.1 infection, whereas all animals previously infected with Delta and exposed to BA.1 became reinfected, although they shed less virus than BA.1-infected naive hamsters. Hamsters reinfected with BA.1 after prior Delta infection emitted infectious virus into the air, indicating that they could be responsible for onwards airborne transmission. We further tested whether prior infection with BA.1 protected from reinfection with Delta or later Omicron sublineages BA.2, BA.4, or BA.5. BA.1 was protective against BA.2 but not against Delta, BA.4, or BA.5 reinfection. These findings suggest that cohorts whose only immune experience of COVID-19 is Omicron BA.1 infection may be vulnerable to future circulation of reemerged Delta-like derivatives, as well as emerging Omicron sublineages.

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“…For hamster infection, SARS-CoV-2 in 100 μL DMEM was intranasally inoculated to hamsters (50 μL per nare). Reported viral inoculation doses ranged from 1 × 10 2 to 1 × 10 7 TCID 50 /mL (38,69,(83)(84)(85)(86) in the literature for different study purposes. However, an ideal dose should mimic the uniform infection in human olfactory epithelium, as displayed in patients with COVID (Figure 5 and 6, by Khan, et al) (5).…”

Section: Methodsmentioning

confidence: 99%

Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants

Chen,

Pekosz,

Villano

et al. 2024

Journal of Clinical Investigation

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SARS-CoV-2 Variant Pathogenesis Following Primary Infection and Reinfection in Syrian Hamsters

Cited by 6 publications

References 70 publications

Genomic Mutations in SARS-CoV-2 Genome following Infection in Syrian Golden Hamster and Associated Lung Pathologies

Genomic Mutations in SARS-CoV-2 Genome following Infection in Syrian Golden Hamster and Associated Lung Pathologies

Omicron breakthrough infections in vaccinated or previously infected hamsters

Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants

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