The SARS-CoV-2 Alpha variant exhibits comparable fitness to the D614G strain in a Syrian hamster model

Abstract

Late 2020, SARS-CoV-2 Alpha variant emerged in United Kingdom and gradually replaced G614 strains initially involved in the global spread of the pandemic. In this study, we use a Syrian hamster model to compare a clinical strain of Alpha variant with an ancestral G614 strain. The Alpha variant succeed to infect animals and to induce a pathology that mimics COVID-19. However, both strains replicate to almost the same level and induced a comparable disease and immune response. A slight fitness advantage is noted for the G614 strain during competition and transmission experiments. These data do not corroborate the epidemiological situation observed during the first half of 2021 in humans nor reports that showed a more rapid replication of Alpha variant in human reconstituted bronchial epithelium. This study highlights the need to combine data from different laboratories using various animal models to decipher the biological properties of newly emerging SARS-CoV-2 variants.

Fig. 1. Clinical follow-up, viral replication in Syrian hamsters and seroneutralization tests.

a Experimental timeline. Groups of 12 hamsters were intranasally infected with 2 × 10³ TCID₅₀ of Alpha variant or G614 strain for comparative assessment, or with a mix (1:1) of both viral strains for competition experiment (10³ TCID₅₀ of each). b Comparative clinical follow-up. Weights are expressed as normalized weights (i.e. % of initial weight). ***, ** and * symbols indicate that normalized weights for the Alpha variant group are significantly higher than those of the G614 group with a p-value ranging between 0.0001–0.001, 0.001–0.01, and 0.01–0.05, respectively (two-way ANOVA test with Tukey’s post-hoc analysis) (n = 12). c–e Comparative assessment of viral RNA yields in lungs (c), nasal washes (d), and guts (e), measured using a RT-qPCR assay. ** and * symbols indicate that viral RNA yields for the Alpha variant group are significantly lower than those of the G614 group with a p-value ranging between 0.001–0.01 and 0.01–0.05, respectively (n = 12; Mann–Whitney and unpaired t tests). f and g Comparative assessment of infectious titers in lungs (f) and nasal washes (g), measured using a TCID₅₀ assay. h and i Competition experiments. Two specific RT-qPCR assays were used to measure the quantity of each virus in lungs (h) and nasal washes (i). Results are expressed as [G614/Alpha variant] ratios. *** and * symbols indicate that ratios at 4 dpi are higher than those at 2 dpi or in inocula with a p-value ranging between 0.0001–0.001 and 0.01–0.05, respectively (n = 12; Mann–Whitney tests). j and k Seroneutralization tests performed with sera from animals sacrificed at 7 dpi. 90% (j) and 99% (k). Yield Reduction Neutralization Titers (90–99YRNT) were determined against four strains of SAR-CoV-2: G614 strain, Alpha variant, Beta variant, and Delta variant. Results from statistical analysis are presented in Supplementary Tables 4–8 (n = 4). b–k Data represent mean ± SD.

Fig. 2. Transmissibility assessment.

a and b Experimental timelines. a A group of 12 hamsters, named ‘donors’, was intranasally infected with an equal proportion of each viral strain for competition experiment (total: 20 TCID₅₀). At 2 dpi, each donor was co-housed with a contact animal during a period of 6 h. Donors and contacts were sacrificed at 3 dpi and at 3 dpc, respectively. b A group of 10 hamsters, named donors, was intranasally infected with a mix (6:14) of G614 strain and Alpha variant for competition experiment (total: 20 TCID₅₀). At 1 dpi, each donor was co-housed with a contact animal during a period of 6 h. Donors and contacts were sacrificed at 1 dpi and at 2 dpc, respectively. c and d Graphical representation of the proportion of each virus found in lungs and nasal washes for each pair of animals in transmission experimentations with 1:1 (c) and 6:14 ratios (d). Two specific RT-qPCR assays were used to measure the quantity of each virus. Gray circles mean that no viral RNA was detected in these nasal washes and lungs.