ARDS is associated with a cytokine storm or the presence of circulatory proinflammatory cytokines. A progression of the disease is characterized as declining viral loads and elevated cytokine levels. Inflammatory responses may play a role in disease immunopathology. Continued research is necessary to understand the severe infections of Covid-19 and develop therapeutics that can prevent unnecessary hospitalizations and lower mortality rates. 

Immunological Implications (In Vivo)

Acute Respiratory Disease, ARDS, can be fatal in certain cases. Severely affected individuals present with a fever, cough, dyspnea and bilateral radiographic opacities (filling of the pulmonary tree with foreign materials). In critically ill patients these pathologies can progress to ARDS. 

Tulane University

In this study performed by the Tulane National Primate Research Center, reports of physiological symptoms similar to patients with severe infections of SARS-CoV-2 were confirmed. Two cases of ARDS in African green monkeys (AGMs) and mild infections in 2 AGMs and 4 RMs infected with Covid-19 were observed. All the AGMs had increased levels of plasma IL-6 and three of the four infected AGMs had high levels of circulating cytokines. All of these factors indicate an immune response similar to those in humans and support the use of AGMs as animal models useful for observing the in vivo effects of ARDS. 

Study of the Application of Green African Monkeys

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

Acute Respiratory Disease

- Virus
- Animals and Procedure
- Histopathologic Scoring
- Immunohistochemistry
- Cytokine Production in Plasma
- Detection of Binding IgG Antibodies in Plasma
- Statistical Analysis

Materials and Methods

Four AGMs and four RMs were exposed to SARS-CoV-2 either through aerosolization or via multiple routes. 
Experimental Group 1:
Four animals exposed to SARS-CoV-2 via small particle aerosol

- AGM1
- AGM4
- RM3
- RM4

Four animals exposed to SARS-CoV-2 via multiple route installation

- AGM2
- AGM3
- RM1
- RM2

RNA from the virus was detected in mucosal swabs and samples from the pharynx and nasal cavity of all eight animals. Analysis of rectal swabs showed high levels of viral RNA. 


Results of the Study

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. 

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