COVID-19 anosmia and transmission mechanisms unravelled in animal study

A recent animal study by the University of Hong Kong (HKU) reveals the mechanism of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may explain the temporary loss of sense of smell following infection. The results show that viral transmission may occur within a short period post-inoculation.

In the study, male golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 isolated from the nasopharyngeal aspirate and throat swab of a patient with confirmed coronavirus disease 2019 (COVID-19) in Hong Kong. Infiltration of mononuclear inflammatory cells and viral antigen for SARS-CoV-2N protein were detected in lower respiratory epithelial tissues at 2–5 days post-inoculation (dpi), followed by rapid clearance of infectious virus by CD3-positive T lymphocytes at 7 dpi. [Nature 2020, doi: 10.1038/s41586-020-2342-5]

A similar inflammatory pattern was observed in nasal turbinate, which led to a reduction in the number of olfactory neurons in the nasal mucosa at 2 dpi and subsequent tissue repairing at 14 dpi, accompanied by presence of viral antigens in nasal epithelial cells and in olfactory sensory neurons. This ability to infect nasal mucosa might explain the temporary anosmia reported in COVID-19 patients.

When three donor hamsters were inoculated intranasally with SARS-CoV-2, with each transferred to a new cage and co-housed with one naïve hamster at 24 hours post-inoculation, transmission of SARS-CoV-2 from donor to naïve hamsters occurred within 6 days. Viral RNA became detectable in nasal washes in co-housed hamsters at 1 day post-contact (dpc), with peak viral load detected at 3 dpc followed by a rapid decline of viral titer. A similar pattern of decline of viral titer was detected from the nasal washes of donor hamsters, whilst viral RNA was continuously detected for 14 days. The onward transmissibility from donors to co-housed contacts was thus correlated with the detection of SARS-CoV-2, but not with viral RNA, in donor nasal washes.

Neutralizing antibodies were detected at 14 dpi and 13 dpc in donors and contacts, respectively. A reversible maximal mean weight loss of 11.97 kg for donor hamsters at 6 dpi and 10.68 kg for naïve hamsters at 6 dpc was observed, respectively.

Transmission of SARS-CoV-2 among hamsters was more efficient via aerosols than with fomites, with infectious virus detectable in nasal washes from contacts at 1 dpc and a peak in viral load detected at 3 dpc via aerosols. Its transmissibility via aerosols was assessed by placing three pairs of donors and naïve aerosol contacts in two adjacent wire cages 1.8 cm apart for 8 hours at 1 dpi, in a single-housed manner.

In contrast, a low titer of infectious virus was detected from the bedding, cage side surface, and water bottle nozzle among naïve fomite contacts who were each introduced to a soiled cage housed by one donor at 0–2 dpi, and then single-housed in soiled cages for 48 hours and each transferred to a new cage at 2 dpc.

“Our findings support recent changes in the criteria used in Hong Kong for discharging COVID-19 patients,” said Dr Hui-Ling Yen of the School of Public Health, HKU. “Results of the animal study not only explain the mechanism of the loss of sense of smell reported by infected patients, but also show that the damage to nasal epithelium and associated neurons is unlikely to be permanent.”