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.

Keywords: SARS-CoV-2; aerosols; inoculation route; nonhuman primate; rhesus macaques.

Figure 1

Clinical score and viral load in rhesus macaques after inoculation with SARS-CoV-2. Animals were inoculated via the intranasal route (blue); exposed to aerosols (orange); or inoculated via the intranasal, intratracheal, oral, and ocular route (gray; historical data from van Doremalen et al [11]). A, Clinical signs were scored daily. Data are presented as median (symbols) with 95% CI (shaded areas). B, Total clinical score for experiment. C, E, Genomic viral RNA detected in nasal swabs and BALF. Data are presented as median (symbols) with 95% CI (shaded areas). Line: qualitative limit of detection. D, F, Total amount of genomic viral RNA shed per animal as measured in nasal swabs and BALF. Bar: median. G, Genomic viral RNA detected in tissue samples collected at 7 days postinoculation. Bar: median. B, D, F, Circle, animal 1; square, animal 2; upward triangle, animal 3; downward triangle, animal 4; diamond, animal 5; hexagon, animal 6. Statistical significance was determined via 2-way analysis of variance with (A, C, E) a Geisser-Greenhouse correction followed by a Tukey multiple-comparisons test or (B, D, F) a Kruskal-Wallis test followed by a Dunn multiple-comparisons test. Asterisks display group-specific differences by color. ***P < .001. **P < .01. *P < .05. BALF, bronchoalveolar lavage fluid; IN, intranasal.