Animal Models for COVID-19: More to the Picture Than ACE2, Rodents, Ferrets, and Non-human Primates. A Case for Porcine Respiratory Coronavirus and the Obese Ossabaw Pig

Abstract

The ongoing COVID-19 pandemic caused by infection with SARS-CoV-2 has created an urgent need for animal models to enable study of basic infection and disease mechanisms and for development of vaccines, therapeutics, and diagnostics. Most research on animal models for COVID-19 has been directed toward rodents, transgenic rodents, and non-human primates. The primary focus has been on the angiotensin-converting enzyme 2 (ACE2), which is a host cell receptor for SARS-CoV-2. Among investigated species, irrespective of ACE2 spike protein binding, only mild (or no) disease has occurred following infection with SARS-CoV-2, suggesting that ACE2 may be necessary for infection but is not sufficient to determine the outcome of infection. The common trait of all species investigated as COVID models is their healthy status prior to virus challenge. In contrast, the vast majority of severe COVID-19 cases occur in people with chronic comorbidities such as diabetes, obesity, and/or cardiovascular disease. Healthy pigs express ACE2 protein that binds the viral spike protein but they are not susceptible to infection with SARS-CoV-2. However, certain pig breeds, such as the Ossabaw pig, can reproducibly be made obese and show most aspects of the metabolic syndrome, thus resembling the more than 80% of the critically ill COVID-19 patients admitted to hospitals. We urge considering infection with porcine respiratory coronavirus of metabolic syndrome pigs, such as the obese Ossabaw pig, as a highly relevant animal model of severe COVID-19.

Phodopus roborovskii SH101 as a systemic infection model of SARS-CoV-2

“…It is made The fever induction and shaking chills are the most common and primary symptoms of COVID-19 that can be observed even in mild cases [26,27]. For the first time, we were able to show the cardinal symptoms of COVID-19, fever induction, shaking chills, and respiratory problems, in a SARS-CoV-2-infected animal just like in the human counterpart (Fig 1 It has been well studied that young animals were significantly less sensitive to SARS-CoV-2 [38,39]. While hACE2 transgenic mice and Syrian hamsters displayed age-dependent sensitivity, SH101 hamsters as young as two-month-old were able to show serious symptoms by SARS-CoV-…”

“…It has been well studied that young animals were significantly less sensitive to SARS-CoV-2 [38,39]. While hACE2 transgenic mice and Syrian hamsters displayed age-dependent sensitivity, SH101 hamsters as young as two-month-old were able to show serious symptoms by SARS-CoV-2 infection (Fig S4 ~ S7).…”

“…Multiple animal species have been investigated as an animal model for COVID-19 since the onset of the pandemic [38,39]. Among the developed animal models to study COVID-19, the hACE2 transgenic mice and Syrian hamsters are the most favorable animal models currently because of the merit of easy handling of small animals [13,15].…”

“…Unfortunately, none of the current COVID-19 animal models reproduce the salient clinical and pathological features of human COVID-19 22 . Even primate models, the closest animal models to humans, did not reproduce the clinical symptoms from the systemic infection of human COVID-19 [16,38]. It is therefore pivotal to develop an animal model for the systemic infection replicating most clinical aspects of human COVID-19.…”

“…Even primate models, the closest animal models to humans, did not reproduce the clinical symptoms from the systemic infection of human COVID-19 [16,38]. It is therefore pivotal to .…”