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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.

SUBMITTER: Munster VJ

PROVIDER: S-EPMC8357058 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Munster Vincent J VJ Flagg Meaghan M Singh Manmeet M Williamson Brandi N BN Feldmann Friederike F Pérez-Pérez Lizzette L Brumbaugh Beniah B Holbrook Myndi G MG Adney Danielle R DR Okumura Atsushi A Hanley Patrick W PW Smith Brian J BJ Lovaglio Jamie J Anzick Sarah L SL Martens Craig C van Doremalen Neeltje N Saturday Greg G de Wit Emmie E

bioRxiv : the preprint server for biology 20210507

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 ...[more]

PMID: 34382034

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Project description:ObjectivesThe clinical outcomes of the Beta (B.1.351) variant of concern (VOC) of the SARS-CoV-2 virus remain poorly understood. In early 2021, northeastern France experienced an outbreak of Beta that was not observed elsewhere. This outbreak slightly preceded and then overlapped with a second outbreak of the better understood VOC Alpha (B.1.1.7) in the region. This situation allowed us to contemporaneously compare Alpha and Beta in terms of the characteristics, management, and outcomes of critically ill patients.MethodsA multicenter prospective cohort study was conducted on all consecutive adult patients who had laboratory confirmed SARS CoV-2 infection, underwent variant screening, and were admitted to one of four intensive care units (ICU) for acute respiratory failure between January 9th and May 15th, 2021. Primary outcome was 60-day mortality. Differences between Alpha and Beta in terms of other outcomes, patient variables, management, and vaccination characteristics were also explored by univariate analysis. The factors that associated with 60-day death in Alpha- and Beta-infected patients were examined with logistic regression analysis.ResultsIn total, 333 patients (median age, 63 years; 68% male) were enrolled. Of these, 174 and 159 had Alpha and Beta, respectively. The two groups did not differ significantly in terms of 60-day mortality (19 vs. 23%), 28-day mortality (17 vs. 20%), need for mechanical ventilation (60 vs. 61%), mechanical ventilation duration (14 vs. 15 days), other management variables, patient demographic variables, comorbidities, or clinical variables on ICU admission. The vast majority of patients were unvaccinated (94%). The remaining 18 patients had received a partial vaccine course and 2 were fully vaccinated. The vaccinated patients were equally likely to have Alpha and Beta.ConclusionsBeta did not differ from Alpha in terms of patient characteristics, management, or outcomes in critically ill patients.Trial registrationClinicalTrials.gov, identifier: NCT04906850.

Dataset Information

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

Publications

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

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