Pathogenicity and transmissibility of SARS-CoV-2-related pangolin coronavirus

In a recent study published in iScience, researchers observed that pangolin coronaviruses (CoVs) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) share similar pathogenicity and transmissibility in hamsters.

Background

SARS-CoV-2, the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic, remains a significant threat to global health even two years after its discovery. The intermediate animal hosts potentially involved in SARS-CoV-2 transmission to humans are poorly understood. A few studies identified pangolin CoVs related to SARS-CoV-2, shedding light on potential intermediate hosts.

Other studies reported that SARS-CoV-2 might have consequently originated by the recombination of viruses similar to pangolin and bat CoVs. Given the exceptionally high sequence similarity of the pangolin CoV’s receptor-binding domain (RBD) to that of SARS-CoV-2, they might pose a significant risk to public health.

The study and results

In the present study, researchers assessed the pathogenic and transmission characteristics of pangolin CoV in Syrian golden hamsters. The pathogenic and transmission features of GX/P2V, a pangolin CoV, were compared to those of SARS-CoV-2 in the hamsters.

When infected with GX/P2V, hamsters did not show substantial weight loss, but SARS-CoV-2-infected animals lost around 5.3% of weight in the first five days-post infections (dpi) and gradually regained weight to the original levels. No animal succumbed to infection with either CoV during the study. Both GX/P2V and SARS-CoV-2 efficiently replicated in hamsters’ respiratory system and brain, exhibiting similar tissue tropism. Infectious viral particles were not detected in the heart, spleen, liver, intestines, kidneys, or fecal matter. The viral titers in the brain and respiratory system peaked during 1 – 2 dpi and dropped subsequently. The replicative features of SARS-CoV-2 were more pronounced than GX/P2V. Viral shedding in the nasal wash of GX/P2V-hamsters was observed for three days compared to five days for SARS-CoV-2-infected animals.

GX/P2V-infected hamsters exhibited widespread thickening of alveolar walls and scattered infiltration of neutrophils and lymphocytes. Contrastingly, SARS-CoV-2-infected animals had severe thickening of alveolar walls with some macrophages. Vascular cuffs were evident around local vessels formed by the annulus of inflammatory cells. The proliferation of epithelial cells in the lungs was extensive with bulged nuclei; simultaneously, nuclear fragmentation and cell necrosis were apparent but to a lesser degree. There were no evident histopathological changes in the turbinate bones of GX/P2V-infected animals.

Conversely, the pseudostratified columnar ciliated epithelium of turbinate mucosa in hamsters infected with SARS-CoV-2 was completely necrotized and exfoliated. GX/P2V-infected hamsters showed hemorrhage in the tracheal submucosa to a smaller extent, whereas the trachea of SARS-CoV-2-infected animals had more pronounced submucosal hyperemia and lymphocytic infiltration. Neither CoV-infected hamsters showed any significant changes in the histopathology of the brain.

The GX/P2V- or SARS-CoV-2-infected hamsters were segregated 24 hours post-inoculation with infectious viral doses into two groups to determine transmission. The infected animals were placed in the same cage as infection-naïve animals for contact transmission evaluation. At the same time, infected animals were kept adjacent to naïve animals, separated by a wireframe cage at a 1.8 cm distance, to study airborne transmission. GX/P2V was detected in naïve animals from the contact group but not the aerosol group. In contrast, SARS-CoV-2 was detected in naïve hamsters from contact and aerosol groups.

Aerosols exhaled by virus-infected hamsters were obtained at different time points. The concentration of the virus peaked at two dpi and decreased gradually. Hardly any viral aerosols were detectable by seven dpi. SARS-CoV-2-infected animals exhaled more virus-laden aerosols than GX/P2V-infected hamsters. For instance, GX/P2V-infected animals released about 367 copies per liter (L) of air with an average of 661 viral particles a minute exhaled by each infected animal. Contrastingly, the concentration of SARS-CoV-2 aerosols was approximately 951.67 copies/L, with 1,713 SARS-CoV-2 particles exhaled by each infected hamster per minute.

Infectious GX/P2V particles were recovered from aerosols > 1 micrometer (μm), whereas SARS-CoV-2 was recovered from aerosols > 0.25 μm. Neutralizing antibodies (nAbs) to GX/P2V were observed in samples collected at five dpi, whereas nAbs against SARS-CoV-2 were noted as early as three dpi. The GX/P2V-induced antibody titers were similar to those elicited by SARS-CoV-2 at five, seven, 14, and 21 dpi but substantially higher at 28 dpi. Three samples with 1:2560 titers were tested for cross-neutralizing potency. Although cross-neutralization was evident for samples from SARS-CoV-2- or GX/P2V-infected animals, the cross-neutralizing titers were lower than self-neutralizing titers.

Conclusions

In the hamster model, the researchers noted similar pathogenic and transmission features between GX/P2V and SARS-CoV-2, albeit relatively weaker for GX/P2V than SARS-CoV-2. Besides the exhalation of virus-laden aerosols, direct contact but not the aerosol transmission was noted for GX/P2V. Given that only GX/P2V was evaluated, these results might not be generalized to other pangolin CoVs, and future work should involve other pangolin CoVs. The authors suggested that the evolution of pangolin CoVs must be monitored in the future.

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.