SARS-CoV-2 infection of non-human primates

National Institute Of Allergy And Infectious Diseases

Investigators

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Abstract

This year we have conducted two major SARS-CoV-2 infection experiments. Manuscripts for both studies are currently under preparation. In the first we used PET-CT imaging to characterize disease progression, and we examined the cellular immune response to SARS-CoV-2 in the infected pulmonary, lymphoid, and upper respiratory tract tissues of rhesus macaques over the first 10 days of infection. Overall, we found that SARS-CoV-2 infection causes mild disease in rhesus macaques. Viral replication peaks in the first 1-3 days and FDG-avid, pulmonary lesions are detectable for the first 3 days of infection. This is consistent with the appearance of a population of activated macrophages in the BAL that peaks around day 3 and returns towards baseline by day 10 as detected by scRNAseq. Despite the subclinical disease, robust Ag-specific T cell responses are detected in the BAL fluid of all the animals, and they displayed typical effector functions expected for antiviral T cells. Of note, we observed major differences in the ability of virus-specific T cells to migrate into infection sites in the upper versus lower respiratory tract. In the second project, we compared the role of pro- and anti-inflammatory cytokines in the regulation of lung disease, viral control and generation of adaptive immune responses. Blockade of the anti-inflammatory molecule increased lung inflammation and the expansion of virus specific T cells. In contrast, blockade of the pro-inflammatory molecule reduced the number and intensity of lung lesions and reduced the levels of virus-specific antibodies. Importantly, blocking the anti- or pro-inflammatory molecules had no effect on viral replication dynamics in any tissue measured. Therefore, we have shown that inflammatory lung disease during SARS-CoV-2 infection can be made worse or better without impacting on viral control.