Ferrets not infected by SARS-CoV-2 in a high-exposure domestic setting

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Ferrets not infected by SARS-CoV-2 in a high-exposure domestic setting

Added 25 November 2020

Sawatzki, K. et al. (2020) Ferrets not infected by SARS-CoV-2 in a high-exposure domestic setting. bioRxiv. https://doi.org/10.1101/2020.08.21.254995

This study reports on the results of a “natural experiment” where 29 ferrets in one home had prolonged, direct contact and constant environmental exposure to two humans with symptomatic COVID-19. The authors observed no evidence of SARS-CoV-2 transmission from humans to ferrets based on RT-PCR and ELISA.

This research was carried out as part of the Coronavirus Epidemiological Response and Surveillance (CoVERS) study, set up at Tufts University to investigate the potential for human-to animal spill over and onward transmission in domestic, farm and wildlife species.

A household with 29 free-roaming ferrets cared for by two adults was enrolled as part of the CoVERS study. Individual 1 experienced fever and fatigue from 25 March-6 April and individual 2 experienced a sore throat, anosmia, migraine and fatigue from 28 March-13 April. Individual 2 tested positive for SARS-CoV-2/COVID-19 infection by nasopharyngeal swab and RT-PCR on 1 April. Individual 1 was a probable positive due to the timing and symptoms but was not tested. Neither person was hospitalised, and both cared for the ferrets during the entirety of their disease courses.

A two-week, in-home sample collection scheme was designed to begin during the household quarantine period, the ferrets were free to move in all spaces of the home during this period and were handled as usual, including regular petting, feeding and grooming.  A home sampling kit sent to the participants including material to safely collect and store ferret oral swabs. One participant had significant animal handling experience and performed all sample collection to standardise sampling procedures. Thirty oral swabs were collected and held in viral transport media in the participants’ freezer until the end of the study period. Frozen samples were directly transferred to a lab member and processed.

Oral swabs were collected from all ferrets in the home over a two-week period, beginning 10 April, concurrent with symptomatic disease in individual 2. One ferret (3) was sampled twice. Two 7-year-old ferrets (12 and 16) died during the study period, one by euthanasia due to chronic disease, the other cause is unknown. Thirty samples from 29 ferret oral swabs were tested by semi-quantitative real time RT-PCR and ELISA.

All samples were confirmed to have viable RNA (by a preliminary screen for constitutively expressed ß-actin) but results of semi-quantitative real time RT-PCR and ELISA were below the limit of detection and determined to be negative for active or recent infection by SARS-CoV-2.

As ferrets have been shown to be susceptible to infection and onward transmission in experimental laboratory infections the researchers undertook further analysis to better understand this discrepancy in experimental and natural infection in ferrets.

They compared SARS-CoV-2 sequences from natural and experimental mustelid infections and identified two surface glycoprotein (Spike) mutations. Evidence found that while ACE2 provides a weak host barrier, one mutation only seen in ferrets is located in the novel S1/S2 cleavage site and is computationally predicted to decrease furin activity. They conclude that the data support that host factors interacting with the  novel S1/S2 cleavage site may be a barrier in ferret SARS-CoV-2 susceptibility and that  domestic ferrets are at low risk of natural infection from currently circulating SARS-CoV-2. This may be overcome in laboratory settings using concentrated viral inoculum, but the effects of ferret host-adaptations require additional investigation.

This study is a pre-print, made available by bioRxiv, as such it is only a preliminary report and has not yet been peer-reviewed

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