Compartmentalized SARS-CoV-2 Replication in the Upper vs Lower Respiratory Tract After Intranasal Inoculation or Aerosol Exposure

Abstract Nonhuman primate models are essential for the development of vaccines and antivirals against infectious diseases. Rhesus macaques are a widely utilized infection model for SARS-CoV-2. We compared cellular tropism and virus replication in rhesus macaques inoculated with SARS-CoV-2 via the intranasal route or via exposure to aerosols. Intranasal inoculation resulted in replication in the upper respiratory tract with limited involvement in the lower respiratory tract, whereas exposure to aerosols resulted in infection throughout the respiratory tract. In comparison with multiroute inoculation, intranasal and aerosol inoculation resulted in reduced SARS-CoV-2 replication in the respiratory tract. Aerosol-inoculated rhesus macaques showed widespread SARS-CoV-2 replication in the respiratory tract, contrasting with limited replication in the upper tract via intranasal inoculation.