Monkey See, Monkey Do: Mimicking COVID-19 in Macaques

A rhesus macaque model of COVID-19 suggests that primates can shed SARS-CoV-2 virus from the nose and stool for nearly a month after infection.

AsianScientist (Dec. 7, 2020) – In a development that could help us understand the transmission of COVID-19 better, researchers from China have established a new rhesus macaque model that mimics SARS-CoV-2 infection via the nose. Their results were published in PLOS Pathogens.

Over the years, animal models have proven be an indispensable tool for biological research. Analyzing the complex interactions among cells, organs and even organ systems in healthy and diseased states requires living organisms ranging from mice and rabbits to the humble fruit fly and even monkeys.

As scientists around the world race to stop the coronavirus, effective animal models are needed more than ever. Primates like rhesus macaques have emerged as a promising animal model in the fight against COVID-19. Given that we share 93 percent of our DNA sequence with macaques, these primates also reflect key features of our bodily systems, including immunity. While macaque models of COVID-19 have previously been explored, these models have yet to address the immune response induced by SARS-CoV-2 infection.

To close this gap, researchers from the Chinese Academy of Medical Sciences and Peking Union Medical College infected macaques with SARS-CoV-2 via the nasal route. Since COVID-19 is a respiratory disease, the nasal route represents a common way of viral transmission.

Remarkably, their results revealed that the virus was shed in the macaques’ nose and stool for up to 27 days. According to the authors, this pattern of long-term viral shedding in macaques is strikingly similar to that observed in so-called COVID-19 ‘long-haulers.’ The team also found another similarity between the COVID-19 human patients and macaque models, namely the progression of interstitial pneumonia—an inflammatory condition marked by lung tissue scarring.

The researchers also noted changes in the T-cell response and levels of cytokine production. T-cells typically carry out multiple functions, including the killing of infected host cells. In this study, the macaques’ T-cells were found to secrete small proteins called cytokines that play a critical role in regulating inflammation.

In fact, two waves of enhanced cytokine production were observed in lung tissue. This finding mirrors the ‘cytokine storm’ observed in many severe COVID-19 cases, where an overproduction of cytokines causes the body to essentially attack itself. Based on these findings, the authors state that T-cell response and changes in cytokine levels should also be used to evaluate the development of COVID-19 vaccines and treatments.

“Several animal models of SARS-CoV-2 focused on revealing the virus shedding period, the development of interstitial pneumonia and virus dissemination in the respiratory tract,” said the authors. “Here, we observed that the response of T-cell subsets and local cytokine changes in the respiratory tract [are] important evaluation parameters for a successful animal model of COVID-19.”

The article can be found at: Zheng et al. (2020) Virulence and Pathogenesis of SARS-CoV-2 Infection in Rhesus Macaques: A Nonhuman Primate Model of COVID-19 Progression.


Source: PLOS; Photo illustration: Lam Oi Keat/Asian Scientist Magazine.
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