Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase
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.
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Supplementary Figure 1: Longitudinal temperature monitoring of SARS-CoV-2 infected AGMs. Temperature was longitudinally monitored for all animals via surgically-implanted temperature loggers (see Materials and methods). Data shown for all animals begins 1 day prior to infection (-1) and terminates in the morning of day 5 post-infection, when AGM-1, AGM-2, and AGM-3 were euthanized. Periods of elevated temperature are indicated in red. Arrows denote time of challenge.
Supplementary Table 1: Clinical description and outcome of African green monkeys following SARS-CoV-2 challenge.
Supplementary Table 2: Gross lung lesion severity scores in AGMs infected with SARS-CoV-2
Posted 13 Aug, 2020
On 18 Aug, 2020
On 07 Aug, 2020
On 07 Aug, 2020
On 06 Aug, 2020
On 06 Aug, 2020
On 30 Jul, 2020
On 29 Jul, 2020
Invitations sent on 29 Jul, 2020
On 29 Jul, 2020
On 28 Jul, 2020
On 28 Jul, 2020
On 27 Jul, 2020
Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase
Posted 13 Aug, 2020
On 18 Aug, 2020
On 07 Aug, 2020
On 07 Aug, 2020
On 06 Aug, 2020
On 06 Aug, 2020
On 30 Jul, 2020
On 29 Jul, 2020
Invitations sent on 29 Jul, 2020
On 29 Jul, 2020
On 28 Jul, 2020
On 28 Jul, 2020
On 27 Jul, 2020
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5