Activity of Tixagevimab/Cilgavimab against the Omicron variant of SARS-CoV-2 in a hamster model (preprint)

The efficacy of pre-exposure prophylaxis by the Tixagevimab/Cilgavimab cocktail (AZD7442) was evaluated in hamsters against a clinical BA.1 strain of SARS-CoV-2 variant Omicron. AZD7442 retains inhibitory activity against Omicron despite a substantial loss of efficacy. We estimate that Omicron virus requires about 20-times more antibodies in plasma than the ancestral B.1 strain (G614) virus to achieve a similar drug efficacy in reducing lung infectious titers.

SARS-CoV-2 20I/501Y.V1 variant in the hamster model (preprint)

Late 2020, SARS-CoV-2 20I/501Y.V1 variant from lineage B.1.1.7 emerged in United Kingdom and gradually replaced the D614G strains initially involved in the global spread of the pandemic. In this study, we used a Syrian hamster model to compare a clinical strain of 20I/501Y.V1 variant with an ancestral D614G strain. The 20I/501Y.V1 variant succeeded to infect animals and to induce a pathology that mimics COVID-19. However, both strains induced replicated to almost the same level and induced a comparable disease and immune response. A slight fitness advantage was noted for the D614G strain during competition and transmission experiments. These data do not corroborate the current epidemiological situation observed in humans nor recent reports that showed a more rapid replication of the 20I/501Y.V1 variant in human reconstituted bronchial epithelium.

Replicative fitness SARS-CoV-2 20I/501Y.V1 variant in a human reconstituted bronchial epithelium (preprint)

Since its emergence in 2019, circulating populations of the new coronavirus continuously acquired genetic diversity. At the end of 2020, a variant named 20I/501Y.V1 (lineage B.1.1.7) emerged and replaced other circulating strains in several regions. This phenomenon has been poorly associated to biological evidence that this variant and original strain exhibit different phenotypic characteristics. Here, we analyse the replication ability of this new variant in different cellular models using for comparison an ancestral D614G European strain (lineage B1). Results from comparative replication kinetics experiments in vitro and in a human reconstituted bronchial epithelium showed no difference. However, when both viruses were put in competition in a human reconstituted bronchial epithelium, the 20I/501Y.V1 variant outcompeted the ancestral strain. Altogether, these findings demonstrate that this new variant replicates more efficiently and could contribute to better understand the progressive replacement of circulating strains by the SARS-CoV-2 20I/501Y.V1 variant. ImportanceThe emergence of several SARS-CoV-2 variants raised numerous questions concerning the future course of the pandemic. We are currently observing a replacement of the circulating viruses by the variant from the United Kingdom known as 20I/501Y.V1 from B.1.1.7 lineage but there is little biological evidence that this new variant exhibit a different phenotype. In the present study, we used different cellular models to assess the replication ability of the 20I/501Y.V1 variant. Our results showed that this variant replicate more efficiently in a human reconstituted bronchial epithelium, which may explain why it spreads so rapidly in human populations.