Abstract
We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.
Highlights
The unprecedented pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has had devastating effects on public health and the global economy
We recently reported the development of the first African green monkey (AGM) model for COVID-19 and showed that backchallenge of animals with SARS-CoV-2 5 weeks after initial exposure resulted in protection from reinfection [10]
We previously reported the development of the AGM as a promising animal model of human COVID-19 [10]
Summary
The unprecedented pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has had devastating effects on public health and the global economy. With the rapid development of 24 preventative vaccines in clinical evaluation [1], and nearly 200 more in the pipeline [2], coupled with the availability of nearly 300 candidate antivirals and disease modulators [2] it is impossible to investigate the safety and efficacy of all of these various interventions in humans. Both small animal models and nonhuman primates (NHP) may prove valuable in triaging the most promising medical countermeasures prior to use in humans. Among the nonhuman primate models evaluated the African green monkey (AGM) appears to best recapitulate the most salient features of human COVID-19 [10,11,12]
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