Infection and Rapid Transmission of SARS-CoV-2 in Ferrets

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease. SARS-CoV-2-infected ferrets exhibit elevated body temperatures and virus replication. Although fatalities were not observed, SARS-CoV-2-infected ferrets shed virus in nasal washes, saliva, urine, and feces up to 8 days post-infection. At 2 days post-contact, SARS-CoV-2 was detected in all naive direct contact ferrets. Furthermore, a few naive indirect contact ferrets were positive for viral RNA, suggesting airborne transmission. Viral antigens were detected in nasal turbinate, trachea, lungs, and intestine with acute bronchiolitis present in infected lungs. Thus, ferrets represent an infection and transmission animal model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines.

Keywords: 2019-nCoV; 2019-novel coronavirus; COVID-19; SARS-CoV-2; ferrets; novel coronavirus disease; severe acute respiratory syndrome coronavirus 2; transmission; virus shedding.

Graphical abstract

Figure 1

Temperature Changes, Weight Loss, Survival, Viral Shedding, and Immunohistochemistry of Tissues of NMC-nCoV02-Infected Ferrets (A–C) Six ferrets were inoculated intranasally with 10^5.5 TCID₅₀ of virus. (A) Temperature changes, (B) number of viral RNA copies, and (C) infectious virus titers were measured in tissues of NMC-nCoV02-infected ferrets (n = 6/group). Each tissue (n = 3 per group) was collected at 4, 8, and 12 dpi. Viral loads in nasal turbinate, trachea, lung, kidney, and intestine were titered using quantitative real-time PCR and TCID₅₀. Data are presented as mean ± SEM. (D) Serum neutralizing (SN) antibody titers (GMT) against NMC-nCoV02 (100 TCID₅₀) were measured onto Vero cells after 12 days of experiment (n = 6 per group). Data are presented as geometric mean ± SD. Tissues were harvested on day 4 after inoculation and immunohistochemistry was performed with a mouse polyclonal antibody. (E–H) Tissues of PBS control ferrets; (E) nasal turbinate, (F) trachea, (G) lung, and (H) intestine. (I–L) Tissues of NMC-nCoV02 infected ferrets: (I) Nasal turbinate, (J) Trachea, (K) lung, and (L) Intestine. The presence of NMC-nCoV02 antigen was determined by IHC with mouse polyclonal antibody. Magnification ×400. Asterisks indicate statistical significance compared with PBS control group by the two-way ANOVA with Sidaks multiple comparisons test (A), the two way ANOVA with Dunnett’s multiple comparisons test (B and C), or one-way ANOVA Dunnett’s multiple comparisons test (^∗ indicates p < 0.05, ^∗∗ indicates p < 0.001, and ^∗∗∗ indicates p < 0.0001).