Upregulation of cytokines was observed in both animals that had manifested ARDS. Furthermore, all 4 AGMS at 7 DPI had increased concentrations of IFN-γ, with the two AGMs with ARDS having the highest plasma concentrations. Thus, increased levels of IFN-γ could be used as a biological predictor of severe disease phenotypes of Covid-19. 

Tulane University

Other studies recently published have demonstrated the progression of SARS-CoV-2 in AGMs and RMs. Both animals are capable of modeling mild to moderate disease and can be used to analyze the efficacy of vaccines and other therapeutics. However, these other studies have not demonstrated the clinical manifestation, ARDS, of the Covid-19 infection. Results of this study show that aged AGMs infected with Covid-19 can develop ARDS (signified by cytokine elevations similar to those in humans). The study’s findings are associated with the results from other studies, with AGMs presenting mild clinical disease, pathology and viral shedding. 

Analysis of Study and Future Research

Blair, R. V., Vaccari, M., Doyle-Meyers, L. A., Roy, C. J., Russell-Lodrigue, K., Fahlberg, M., . . . Rappaport, J. (2021). Acute respiratory distress in aged, sars-cov-2–infected african green monkeys but not rhesus macaques. The American Journal of Pathology, 191(2), 274-282. doi:10.1016/j.ajpath.2020.10.016

Acute Respiratory Distress in Aged, SARS-CoV-2–Infected African Green Monkeys but Not Rhesus Macaques

The RMs, similar to the AGMS, exhibited mild manifestations of the disease and shorter viral shedding from mucosal sites. Thus, these findings support the conclusion that both AGMs and RMs can be used for testing SARS-CoV-2 vaccines and therapeutics. 

AGMs are Successful Animal Models

Two of the AGMs developed acute respiratory distress (measured by oxygen saturation through pulse oximetry, 77%) that progressed over a 24-hour period. Postmortem findings, of alveolar damage with no evidence of congestive heart disease, support the diagnosis of ARDS in AGM1 and AGM2. The authors make note of the health implications of procedure-related complications; however, there is sufficient evidence to support that routine laboratory protocols do not cause ARDS, despite procedural complications. Increases in plasma cytokines, indicative of a cytokine storm, were found in the AGMs that had progressive ARDS. 

Manifestation of ARDS in AGMs

Proinflammatory cytokines had been elevated during the acute phases of lung damage. These observable cytokines include:

- Tumor necrosis factor-α
- IL-1β
- IL-8
- IL-6 (in human infection, this cytokine relates to abnormalities of pneumonia observed in radiographic imaging)
- Granulocyte colony-stimulating factor
- Monocyte chemoattractant protein 1
- Macrophage inflammatory protein 1


Evidence of Cytokine Production

Elevated IFN-γ

Several factors, including age, weight and sex, are predisposing factors for developing this particular clinical manifestation of Covid-19. All the AGMs were aged, with a median age of 16 years, and animals that progressed to the severe disease phenotype were female with low weight. This data differs with patients who developed ARDS, where the male sex and obesity is correlated with a higher prevalence of ARDS. In this study, the AGMs were imported from nondomestic sites and remained at the Tulane National Primate Research Center. Although they were physically healthy at the start of the study, historical factors may have predisposed the animals to ARDS.  

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