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

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 spike. 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. 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.