Subtle differences in the pathogenicity of SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 in rhesus macaques

Abstract

The emergence of several SARS-CoV-2 variants has caused global concerns about increased transmissibility, increased pathogenicity, and decreased efficacy of medical countermeasures. Animal models can be used to assess phenotypical changes in the absence of confounding factors that affect observed pathogenicity and transmissibility data in the human population. Here, we studied the pathogenicity of variants of concern (VOC) B.1.1.7 and B.1.351 in rhesus macaques and compared it to a recent clade B.1 SARS-CoV-2 isolate containing the D614G substitution in the spike protein. The B.1.1.7 VOC behaved similarly to the D614G with respect to clinical disease, virus shedding and virus replication in the respiratory tract. Inoculation with the B.1.351 isolate resulted in lower clinical scores in rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. We observed differences in the local innate immune response to infection. In bronchoalveolar lavages, cytokines and chemokines were upregulated on day 4 in animals inoculated with D614G and B.1.1.7 but not in those inoculated with B.1.351. In nasal samples, we did not detect upregulation of cytokines and chemokines in D614G or B.1.351-inoculated animals. However, cytokines and chemokines were upregulated in the noses of B.1.1.7-inoculated animals. Taken together, our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity.

mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates

“… 36 , 40 , 42 , 48 , 51 and is higher than viral loads typically seen in human infections. Whether the amount and persistence of the B.1.351 virus in vivo in this study relates to the challenge dose or suggests that this variant has inherent properties that make it more difficult to control and clear compared to the WA-1 strain 53 , 54 is a focus of ongoing analyses.…”

“…This contrasts with the more rapid and complete reduction of viral replication following challenge with the WA-1 strain 36 , 40 , 42 , 48 , 51 and is higher than viral loads typically seen in human infections. Whether the amount and persistence of B.1.351 virus in vivo in this study relates to challenge dose or suggests that this variant has inherent properties that make it more difficult to control and clear compared to the WA-1 strain 53 , 54 is a focus of ongoing analyses. 36 , 40 , 42 , 48 , 51 and is higher than viral loads typically seen in human infections.…”

Advances and gaps in SARS-CoV-2 infection models

“…Importantly, even though VOCs readily infected the lower respiratory tract of hamsters and NHPs, none of these variants seemed to show enhanced virulence in these animal models, although increased production of proinflammatory cytokines was observed in hamsters infected with the alpha VOC [ 9 ]. In a comparative study carried out in rhesus macaques, infection with the beta VOC resulted in lower clinical scores and lower levels of virus replication in comparison with ancestral B.1 virus and alpha VOC [ 31 ]. These findings were confirmed in a direct comparison between B.1 and alpha VOC infection in African green monkeys [ 32 ].…”

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

“…B.1.1.7 variant showed comparable lung pathology in hamster model in comparison to B.1 [ 17 ]. Also B.1.1.7 and B.1.351 studies in hamster and non-human primate models did not show any increased disease severity [ 17 , 21 , 22 ]. In contrary, here we observed severe pneumonic changes associated with a variant of interest i.e., Brazil P2 variant.…”