SARS-CoV-2 Delta Variant Pathogenesis and Host Response in Syrian Hamsters

Abstract

B.1.617 is becoming a dominant Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) lineage worldwide with many sublineages, of which B.1.617.2 is designated as a variant of concern. The pathogenicity of B.1.617.2 (Delta) and B.1.617.3 lineage of SARS-CoV-2 was evaluated and compared with that of B.1, an early virus isolate with D614G mutation in a Syrian hamster model. Viral load, antibody response, and lung disease were studied. There was no significant difference in the virus shedding pattern among these variants. High levels of SARS-CoV-2 sub genomic RNA were detected in the respiratory tract of hamsters infected with the Delta variant for 14 days, which warrants further transmission studies. The Delta variant induced lung disease of moderate severity in about 40% of infected animals, which supports the attributed disease severity of the variant. Cross neutralizing antibodies were detected in animals infected with B.1, Delta, and B.1.617.3 variant, but neutralizing capacity was significantly lower with B.1.351 (Beta variant).

Keywords: B.1.617.2; B.1.617.3; Delta variant; SARS-CoV-2; Syrian hamster; pathogenicity.

Figure 1

Bodyweight and virus shed by hamsters post challenge with SARS-CoV-2 variants. (a) Percent body weight changes in hamsters post virus infection at days 3 (n = 18); 5 (n = 14); 7 (n = 10); and 10, 12, and 14 (n = 6), as well as in mock control hamsters (n = 4). Viral genomic RNA load (log₁₀ viral genomic RNA copy numbers/mL) in (b) throat swab, (c) nasal wash, and (d) faeces samples collected on 3, 5, 7, 10, 12, and 14 days post infection (DPI). Viral sub genomic mRNA load (log₁₀ viral subgenomic RNA copy numbers/mL) in (e) throat swab, (f) nasal wash, and (g) faeces in hamsters post virus challenge on 3, 5, 7, 10, 12, and 14 DPI. The mean along with standard deviation is depicted in the scatter plot. The statistical significance was assessed using the non-parametric Mann–Whitney tests and p-values less than 0.05 were considered to be statistically significant. The dotted line indicates the limit of detection of the assay.

Figure 2

Viral load in respiratory tract samples of hamsters post infection. Viral genomic RNA load (log₁₀ viral genomic RNA copies/mL) in (a) nasal turbinates, (b) trachea, and (c) lung samples collected on 3, 5, 7, and 14 DPI, represented as mean with standard deviation in a scatter plot. Viral sub genomic RNA load (log₁₀ viral subgenomic RNA copies/mL) in (d) nasal turbinates, (e) trachea, and (f) lung samples collected on 3, 5, 7, and 14 DPI, represented as mean with standard deviation in a scatter plot. The statistical significance was assessed using the non-parametric Mann–Whitney tests, and p-values less than 0.05 were considered to be statistically significant. The dotted line indicates the limit of detection of the assay.

Figure 3

Antibody response in hamsters post challenge with SARS-CoV-2 variants. (a) Anti-SARS-CoV-2 IgG response in hamsters post virus infection by ELISA. Neutralizing antibody response in hamsters infected with the (b) B.1, (c) B.1.617.2 (Delta), and (d) B.1.617.3 variants against B.1, Delta, B.1.617.3, and B.1.351 (Beta). The dotted line indicates the limit of detection of the assay. The mean along with standard deviation is depicted in the scatter plot. The statistical significance was assessed using the non-parametric Mann–Whitney tests, and p-values less than 0.05 were considered to be statistically significant.

Figure 4

Pathological changes in lungs observed at necropsy in hamsters post infection with the B.1, Delta, and B.1.617.3 variants. (a) Proportion of lung weight to body weight of hamsters at necropsy represented as mean with standard deviation. (b) Cumulative lung histopathology score in hamsters infected with SARS-CoV-2 variants represented as mean with standard deviation. Lungs of Delta variant-infected hamsters showing (c) diffuse alveolar damage with congestion and hemorrhages in the lung parenchyma, as well as (d) diffuse mononuclear infiltration, pneumocyte hyperplasia and septal thickening with mild congestion. Lungs of B.1.617.3 infected hamsters showing (e) alveolar septal thickening, exudation and hyaline changes in the alveoli, as well as (f) congestion and alveolar septal thickening. Lungs of B.1 infected hamster showing (g) few small foci of mononuclear cell infiltration and (h) congestion and perivascular inflammatory cell infiltration.