Vaccination against SARS-CoV-2 Does Not Protect against the Development of Anosmia in a Hamster Model

Abstract

Anosmia, a total or partial loss of the ability to smell, is one of the most frequently documented sequelae of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Persistent anosmia is associated with a decrease in quality of life. Here, we assess the impact of virus lineage and vaccination status on anosmia development in the golden Syrian hamster model. To characterize anosmia driven by current variants, we assessed olfactory function in hamsters infected with SARS-CoV-2 lineages A, BA.2, BA.5, BQ.1, and BQ.1.1 using a buried food detection test. We found that significant anosmia occurs upon infection with all variants with a significant correlation between disease severity and degree of anosmia. Moreover, we found that vaccination with either the Pfizer (BNT16b2) or Moderna (mRNA-1273) mRNA vaccines does not protect against anosmia, despite protection against severe disease.

Keywords: SARS-CoV-2; anosmia; sequelae; vaccination.

Figure 1

Omicron variants induce a milder acute disease than the ancestral variant in golden Syrian hamsters, yet still present with significant anosmia. (A) percentage weight change in hamsters intranasally infected with 10⁴ PFU of variant A, BA.2, BA.5, BQ.1, or BQ.1.1 SARS-CoV-2 or mock infected with PBS. n = 8 per infection group and n = 16 for PBS. Data presented as mean ± SEM. Significant differences in weight change as compared to the PBS group were determined using a two-way ANOVA followed by Dunnett’s multiple comparisons test; the degree of these significant differences is denoted in the table to the right of the graph. (B) viral load in nasal wash samples collected at 5 dpi. Symbols represent individual subjects, midlines represent the mean, and error bars represent the standard deviation. Dashed line represents the lower limit of detection for the assay. (C) the time taken for hamsters to find a buried cookie. Data presented as box plots with individual values. The midlines represent the median values and the error bars represent the range of maximum and minimum values. The maximum detection time was 300 s. n = 8 per infection group and n = 16 for PBS. Significance was analyzed using a one-way ANOVA followed by the Dunnett post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. NS—not significant.

Figure 2

Vaccination with Pfizer (BNT16b2) or Moderna (mRNA-1273) prevents against severe disease in golden Syrian hamsters. (A,B) percentage weight change in vaccinated hamsters infected with 10⁴ PFU of BQ.1 or WA-1. n = 8 per infection group and n = 24 for mock. The mock group is pooled data from Pfizer, Moderna, and sham vaccinated uninfected controls. Data presented as mean ± SEM. Significance was determined using a two-way ANOVA followed by Dunnett’s multiple comparisons test; the degree of these significant differences is denoted in the table to the right of the graph. (C,D) lung titers collected at the endpoint (5 dpi). Significance was assessed using a one-way ANOVA followed by the Tukey post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. NS—not significant.

Figure 3

Vaccination does not significantly reduce severity of anosmia. The time taken for hamsters to find a buried Teddy Graham cookie at 5 dpi. Data presented as box plots with individual values. The maximum detection time was 300 s. n = 8 per infection group and n = 24 for the mock-infected group. Significance was analyzed using a one-way ANOVA followed by the Dunnett post hoc test. * p < 0.05, ** p < 0.01, **** p < 0.0001.