Pulmonary lesions following inoculation with the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant in Syrian golden hamsters

Abstract

The Omicron BA.1 (B.1.1.529) SARS-CoV-2 variant is characterized by a high number of mutations in the viral genome, associated with immune escape and increased viral spread. It remains unclear whether milder COVID-19 disease progression observed after infection with Omicron BA.1 in humans is due to reduced pathogenicity of the virus or due to pre-existing immunity from vaccination or previous infection. Here, we inoculated hamsters with Omicron BA.1 to evaluate pathogenicity and kinetics of viral shedding, compared to Delta (B.1.617.2) and to animals re-challenged with Omicron BA.1 after previous SARS-CoV-2 614G infection. Omicron BA.1 infected animals showed reduced clinical signs, pathological changes, and viral shedding, compared to Delta-infected animals, but still showed gross- and histopathological evidence of pneumonia. Pre-existing immunity reduced viral shedding and protected against pneumonia. Our data indicate that the observed decrease of disease severity is in part due to intrinsic properties of the Omicron BA.1 variant.

In vitro and in vivo differences in neurovirulence between D614G, Delta And Omicron BA.1 SARS-CoV-2 variants

“…Within the affected olfactory epithelium and lamina propria, predominantly neutrophilic infiltrates were present and the associated turbinates’ lumina contained substantial mucopurulent exudates. As previously reported by Rissmann et al and others, [ 9 , 48 , 49 ] Delta or Omicron BA.1 inoculated hamsters exhibited fewer histological lesions compared to D614G in the respiratory tract. Omicron BA.1 inoculated hamsters showed the mildest inflammatory lesions within the olfactory mucosa.…”

“…This study indicates notable differences in the neuroinvasiveness, neurotropism and neurovirulence between the ancestral D614G and the Delta and Omicron BA.1 SARS-CoV-2 variants using in vitro hiPSC derived neural cultures and in vivo Syrian golden hamster model. The hamster model has been proven useful for studying the pathogenesis of respiratory disease caused by infection with different SARS-CoV-2 variants [ 9 , 25 – 28 , 50 ]. Methodologically, our current findings also confirm the value of parallel investigations of the neuroinvasiveness and neurovirulence of different SARS-CoV-2 variants in animal models and hiPSC-derived models.…”

“…However, the observed abundant replication of D614 within the olfactory mucosa and the associated lesions likely contribute to anosmia. Interestingly, anosmia was observed more frequently in humans after infection with viruses containing the D614G mutation early in the pandemic [ 60 ] and recent findings suggest that anosmia occurs less frequently after infection with Omicron BA.1 compared to earlier variants [ 9 – 12 ]. Although these findings require replication and independent validation, these observations are in accordance with the less efficient replication of Omicron BA.1 in the olfactory mucosa compared to D614G [ 18 , 61 ].…”

“…The time point of 5 dpi was chosen to represent the peak of respiratory and clinical manifestation of disease. Furthermore, based on literature [ 28 , 45 ] and our previous studies by Rissmann et al [ 9 ] we assumed that the 5 dpi would facilitate both viral detection and evidence of inflammatory changes within the CNS. Mock infected animals were euthanized 14 days post mock infection.…”

“…Currently, it is unclear whether (emerging) SARS-CoV-2 variants differ in their neuroinvasiveness, neurotropism and neurovirulence. However, several studies have shown that in mice and hamsters respiratory disease is less severe after inoculation with Omicron BA.1 variant compared to earlier variants [ 9 – 12 ], and epidemiological data suggest that hospitalization rates are lower with the Omicron BA.1 variant compared to earlier SARS-CoV-2 variants [ 13 , 14 ]. Indirect evidence suggest that neurological complications in humans might be less common after infection with Omicron BA.1 compared to earlier variants such as D614G or the Delta variant, since both anosmia and Long Covid occur less frequently, although this might be—in part—related to pre-existing immunity [ 15 – 18 ].…”