Age-Related Susceptibility of Ferrets to SARS-CoV-2 Infection

Abstract

Susceptibility to SARS-CoV-2 and the outcome of COVID-19 have been linked to underlying health conditions and the age of affected individuals. Here we assessed the effect of age on SARS-CoV-2 infection using a ferret model. For this, young (6-month-old) and aged (18-to-39-month-old) ferrets were inoculated intranasally with various doses of SARS-CoV-2. By using infectious virus shedding in respiratory secretions and seroconversion, we estimated that the infectious dose of SARS-CoV-2 in aged animals is ∼32 plaque forming units (PFU) per animal while in young animals it was estimated to be ∼100 PFU. We showed that viral replication in the upper respiratory tract and shedding in respiratory secretions is enhanced in aged ferrets when compared to young animals. Similar to observations in humans, this was associated with higher transcription levels of two key viral entry factors - ACE2 and TMPRSS2 - in the upper respiratory tract of aged ferrets. Importance In humans, ACE2 and TMPRSS2 are expressed in various cells and tissues, and a differential expression have been described in young and old people, with a higher level of expressing cells being detected in the nasal brushing of older people when compared to young individuals. We described the same pattern occurring in ferrets and we demonstrated that age affects susceptibility of ferrets to SARS-CoV-2. Aged animals were more likely to get infected when exposed to lower infectious dose of the virus when compared to young animals and the viral replication in the URT and shedding is enhanced in aged ferrets. Together these results suggest that the higher infectivity and enhanced ability of SARS-CoV-2 to replicate in aged individuals is associated – at least in part – with transcription levels of ACE2 and TMPRSS2 at the sites of virus entry. The young and aged ferret model developed here may represent a great platform to assess age-related differences in SARS-CoV-2 infection dynamics and replication.

From Deer-to-Deer: SARS-CoV-2 is efficiently transmitted and presents broad tissue tropism and replication sites in white-tailed deer

“…The high amounts of infectious virus recovered from nasal turbinate and tonsils (viral titers ranged from 3.3 to 6.5 log10 TCID 50 .g -1 ) are consistent with intense viral RNA and N protein staining observed in situ and with the viral load and shedding patterns detected in respiratory secretions. This indicates that nasal turbinate and tonsil are likely the primary sites of viral replication during infection in WTD, which is similar to observations in other animal species and in humans [ 19 , 26 – 29 ]. Following infection and replication in these sites, the virus likely disseminates to draining lymph nodes, the lower respiratory (trachea and lung) tract and the CNS.…”

“…Our study extends the knowledge regarding SARS-CoV-2 infection dynamics in WTD, an animal species with the potential to serve as a reservoir for the virus in the field. We defined that SARS-CoV-2 has a short window of infectivity and transmissibility in WTD, which is similar to what has been described in humans and other animal species [ 19 , 21 , 27 , 29 , 36 – 38 ], and demonstrated that the virus presents a broad tissue tropism and multiple replication sites in this species. This information is critical to assess the relevance of natural SARS-CoV-2 infections in WTD populations and the potential risk of zoonotic spillback into humans.…”

ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points

“…Finally, studying older patients might determine whether the upregulation of ACE2 or the decrease in antibodies with senescence is significant ( 10 , 57 ). Moreover, the implications of ACE2 upregulation would lead to specific studies based on different symptoms in old and young patients.…”

“…The first study described a significant expression of ACE2 in older males in both mouse models and human organs ( 10 ). The second study demonstrated the overexpression of ACE2 and TMPRSS2 in the upper respiratory tract of aged ferrets compared to young animals ( 57 ). Moreover, a recent study found that ACE2 levels increase during aging in mouse and human lungs due to telomere shortening or dysfunction ( 58 ).…”

“…While aging decreases plasma levels of antibodies, studies have demonstrated increased ACE2 and TMPRSS2 expression in older adults ( 10 , 57 ). The first study described a significant expression of ACE2 in older males in both mouse models and human organs ( 10 ).…”