Pathology and Immunity After SARS-CoV-2 Infection in Male Ferrets Is Affected by Age and Inoculation Route.

Koen Van De Ven,Tanja Schouten,Paul Roholl,Puck B Van Kasteren,Stefanie Lenz,Jolanda Kool,Lisa Wijsman,Angéla Gomersbach,Jørgen De Jonge,Harry Van Dijken,Adam Meijer

doi:10.3389/fimmu.2021.750229

Koen Van De Ven, Tanja Schouten + Show 9 more

Open Access

https://doi.org/10.3389/fimmu.2021.750229

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Abstract

Improving COVID-19 intervention strategies partly relies on animal models to study SARS-CoV-2 disease and immunity. In our pursuit to establish a model for severe COVID-19, we inoculated young and adult male ferrets intranasally or intratracheally with SARS-CoV-2. Intranasal inoculation established an infection in all ferrets, with viral dissemination into the brain and gut. Upon intratracheal inoculation only adult ferrets became infected. However, neither inoculation route induced observable COVID-19 symptoms. Despite this, a persistent inflammation in the nasal turbinates was prominent in especially young ferrets and follicular hyperplasia in the bronchi developed 21 days post infection. These effects -if sustained- might resemble long-COVID. Respiratory and systemic cellular responses and antibody responses were induced only in animals with an established infection. We conclude that intranasally-infected ferrets resemble asymptomatic COVID-19 and possibly aspects of long-COVID. Combined with the increasing portfolio to measure adaptive immunity, ferrets are a relevant model for SARS-CoV-2 vaccine research.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in patients near the end of 2019 and soon started a new pandemic [1]
In this study we assessed the role of age and infection route on SARS-CoV-2 disease and immunity in ferrets, in an attempt to model the COVID-19 observed in humans
A slightly more watery defecation was observed in some animals towards the end of the study, but occurrences were too few to confidently attribute this to SARS-CoV-2 infection

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in patients near the end of 2019 and soon started a new pandemic [1]. Effective SARS-CoV-2 vaccines were rapidly developed and implemented. Many of these vaccines have proven to be effective in limiting mortality and morbidity [2], it remains a point of concern that SARS-CoV-2 mutants might escape vaccine-induced immunity [3]. Much remains unknown about the pathology and long-term effects of SARS-CoV-2 infection and protective immunity. Animal models are essential for investigating these issues and the scientific community has made unprecedented advances in their development since the outbreak [4, 5]. There are still some remaining knowledge gaps that limit the evaluation of outstanding questions

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