Comparative infectivity and pathogenesis of emerging SARS-CoV-2 variants in Syrian hamsters

Abstract

Within one year after its emergence, more than 108 million people contracted SARS-CoV-2 and almost 2.4 million succumbed to COVID-19. New SARS-CoV-2 variants of concern (VoC) are emerging all over the world, with the threat of being more readily transmitted, being more virulent, or escaping naturally acquired and vaccine-induced immunity. At least three major prototypic VoC have been identified, i.e. the UK (B.1.1.7), South African (B.1.351) and Brazilian (B.1.1.28.1), variants. These are replacing formerly dominant strains and sparking new COVID-19 epidemics and new spikes in excess mortality. We studied the effect of infection with prototypic VoC from both B.1.1.7 and B.1.351 lineages in Syrian golden hamsters to assess their relative infectivity and pathogenicity in direct comparison to two basal SARS-CoV-2 strains isolated in early 2020. A very efficient infection of the lower respiratory tract of hamsters by these VoC is observed. In line with clinical evidence from patients infected with these VoC, no major differences in disease outcome were observed as compared to the original strains as was quantified by (i) histological scoring, (ii) micro-computed tomography, and (iii) analysis of the expression profiles of selected antiviral and pro-inflammatory cytokine genes. Noteworthy however, in hamsters infected with VoC B.1.1.7, a particularly strong elevation of proinflammatory cytokines was detected. Overall, we established relevant preclinical infection models that will be pivotal to assess the efficacy of current and future vaccine(s) (candidates) as well as therapeutics (small molecules and antibodies) against two important SARS-CoV-2 VoC.

Naturally-acquired immunity in Syrian Golden Hamsters provides protection from re-exposure to emerging heterosubtypic SARS-CoV-2 variants B.1.1.7 and B.1.351

“…This suggests a slightly increased pathogenicity in the two VOC as compared with the LIV strain. Others have reported very similar pathogenesis of B.1.1.7 and B.1.351 in the hamster model, with perhaps minor differences in terms of increased upper-respiratory tract replication and increase cytokine production in B.1.1.7-infected animals 25,26 . Accordingly, more detailed studies will be required to define the difference in pathogenesis between these strains.…”

“…Thus, in spite of concerns regarding the effectiveness of naturally-acquired antibodies in neutralising new VOC, our results suggest that the overall immune response from a B strain is diverse enough to protect from clinical signs after re-challenge with the current VOC. cytokine production in B.1.1.7-infected animals 25,26 . Accordingly, more detailed studies will be required to define the difference in pathogenesis between these strains.…”

Isolation of SARS-CoV-2 B.1.1.28.2 P2 variant and pathogenicity comparison with D614G variant in hamster model

“…COVID-19 in hamsters is characterized by respiratory signs, body weight loss and pneumonia[20]. Hamster model has been used to assess the infectivity and pathogenicity of SARS-CoV-2 VOCs like B.1.1.7, B.1.351, B.1.617etc[18,21]. The variant specific differences can be evaluated with this model using criteria’s like viral load, histological scoring, inflammatory cytokine level etc[18,21].…”

“…Hamster model has been used to assess the infectivity and pathogenicity of SARS-CoV-2 VOCs like B.1.1.7, B.1.351, B.1.617etc[18,21]. The variant specific differences can be evaluated with this model using criteria’s like viral load, histological scoring, inflammatory cytokine level etc[18,21]. B.1.1.28.2 variant induced body weight loss and supported viral replication in respiratory tract.…”

Drug development of an affinity enhanced, broadly neutralizing heavy chain-only antibody that restricts SARS-CoV-2 in rodents

“…6e, and Supplementary Table 1 were performed with SARS-CoV-2 strain BetaCov/Belgium/GHB-03021/2020 (EPI ISL 407976; 2020-02-03) used from passage P6 grown on VeroE6 cells 20 . SARS-CoV-2 viruses belonging to the VoC UK and South African lineages B.1.1.7 (hCoV-19/Belgium/rega-12211513/2020; EPI_ISL_791333, 2020-12-21) and B.1.351 (hCoV-19/Belgium/rega-1920/2021; EPI_ISL_896474, 2021-01-11) were each isolated from nasopharyngeal swabs taken from travelers returning to Belgium in December 2020 and January 2021, respectively, and have recently been described 79 . B.1.1.7 was from a healthy subject and B.1.351 from a patient with respiratory symptoms.…”