Table 3.
Summary of publications using rhesus macaque models of COVID-19.
| Number, species,§, gender, age | Virus strain, inoculation route†, (number exposed) | Clinical signs, (dpi)* | Gross and histologic lung pathology#, dpi* euthanized | Viral detection‡, (dpi)* | (Ref) |
|---|---|---|---|---|---|
| 13 RM M/F 6-12 y (Sex ratio not listed) | 2019-nCoV/USA-WA1-A12/2020 Combined IN, IT | Refer to Table 4 Reference 11 | 2 euthanized 2 and 4 dpi Lung consolidation, inflammation, endothelialitis, Microthrombi and fibrin in alveolar septae, endothelial hyperplasia narrowing vessel lumina, collagen I deposition in lung parenchyma, -vWF throughout lung | Refer to Table 4 Reference 11 | 2 |
| 4 RM 3 M/ 1 F 13-15 y | 2019-nCoV/USA-WA1-A12/2020 Aerosol (2) Combined IT, IN, PO, CJ (2) | Mild transient change in temperature and SpO2- Appetite | Euthanized 27-28 dpi 3/ 4 grossly normal 1/ 4 focal pulmonary scar in right caudal lung lobe surrounded by acute hemorrhage 4/4 minimal to mild interstitial inflammation | Nose, throat, rectum (2-7) Shorter viral shedding from mucosal sites when compared with AGMs | 6,34 |
| 5 RM 5M 3-5 y | SARS-CoV-2/WH-09/ human/ 2020/CHN CJ (2) IT (1) IG (2) | No clinical signs reported | 1 of each route euthanized at 7 dpi CJ: mild, focal, interstitial pneumonia, minimal alveolar exudate IT: moderate, diffuse interstitial pneumonia, - alveolar exudate and inflammation GI: None | CJ /IT: nose/ throat (1-7) CJ: conjunctiva (1) IG none CJ - virus load in nasolacrimal and ocular tissues IT- virus in lung | 27 |
| 4 RM M/ F Adult (Sex ratio not listed) | 2019-nCoV/USA-WA1/2020 Aerosol | 4/4 - respiratory sounds 3/ 4 Mild hypoxia, periocular erythema 1/4 increased respiratory effort | Euthanized 8 dpi Gross: Not described Histopathology: 3/3 DAD | Nose, throat (3) Rectal swab (3 7) | 53 |
| 8 Chinese RM 4 M/ 4 F 3-6 y | SARS-CoV-2 Korean isolate Combined IT, IN, CJ, IV | 3/ 4 -activity (data acquired on 4/8 RM with activity collars) 6/8 -temperature (1-3) | 4 euthanized at 4 dpi Multifocal interstitial pneumonia, endotheliitis | Highest in respiratory swabs and lung tissue early in infection | 58 |
| 14 RM | SARS-CoV-2 from CDC, Guangdong Province China Combined IT, IN, CJ | 11/14 -temperature 11/14 weight loss at 10 dpi (5.88% to 28.57%) | Euthanized | Nose (2-14) | 67 |
| 4 Juvenile | 1 adult at 4, 7 and 12 dpi | ||||
| 6 Adult | 1 Juvenile and 1 old at 14 dpi | Blood (2-10) | |||
| 4 Old (Sex ratio not listed) | Interstitial pneumonia, diffuse hemorrhage and necrosis in lung, hilar and mesenteric lymphadenopathy | Prolonged viral shedding in feces | |||
| More interstitial pattern on radiographs in old than juvenile RM | |||||
| 8 RM 4 M/ 4 F Adult | SARS-CoV-2 isolate nCoV-WA1–2020 Combined IT, IN, PO, CJ | 8/8 piloerection, - appetite, hunched posture, tachypnea/ dyspnea, weigh loss 8/8-Temperature 1 dpi, then returned to normal | 4 euthanized 3 dpi and 4 at 21 dpi Pulmonary edema, mild to moderate interstitial pneumonia, DAD | Serum (10) | 79 |
| 6 RM 3 M/ 3 F 2-4 y | SARS-CoV-2/ Victoria/01/2020 IT, IN | None | Euthanized: | Nose and Throat (2) | 96 |
| 2 NHP at 4/5 dpi | BALF (4-5) | ||||
| 2 NHP at 14/15 dpi | Rectum (1-9) | ||||
| 2 NHP at 18/19 dpi | 1/6 Whole blood (3) | ||||
| Gross: Mild to moderate consolidation | |||||
| Histopathology: Multifocal to coalescing interstitial pneumonia, DAD | |||||
| 16 RM 8 Juvenile | SARS-CoV-2 isolate USA-WA1/2020 | 4 used acutely (2 juvenile/ 2 old) euthanized 3 dpi: No fever or weight loss, -serum C-reactive protein and serum CO2 12 euthanized 14–17 dpi (6 juvenile, 6 old juvenile): Same as acute study, but majority lost weight | Acute 3 dpi: | Acute 3 dpi: Nose, mouth, BALF | 106 |
| 4 M/ F | Combined | 3/ 4 no gross abnormalities | (1-3) | ||
| 8 Old | IT, IN, CJ | 1/ 4 multifocal to coalescing red discoloration left lung lobes | 14-17 dpi: 10/12 BALF (3) | ||
| 2 M/ 4 F | ** IN, IT via mucosal atomization device | Histopathology: multifocal mild to moderate interstitial pneumonia, fibrin deposition, edema, vasculitis, necrosis, consolidation | 6/12 Nose (3-17) | ||
| 14-17 dpi group: grossly unremarkable, histopathology similar | 2/12 Rectum (3-9) None in serum | ||||
| 5 RM 3 juvenile 3-5 y 2 Aged 15 y (Sex ratio not listed) | BetaCoV/Wuhan/IVDC-HB-01/2020 IT | 4/5 weight loss, lethargy | 1 juvenile and 1 aged euthanized 7 dpi Juvenile: interstitial pneumonia | Rectum (3-11) | 140 |
| Aged: Diffuse, severe, interstitial pneumonia, more viral antigen in lung than juvenile RM | Respiratory tract (3) | ||||
| 8 Chinese RM 4 M 5 y 4 M >16 y | SARS-CoV-2/ strain 107/ Guangdong ChinaIT | Juvenile Adults: no clinical signs, - respiratory rate, -pCO2, fever 11 dpi Aged Adults: Weight loss 5-11 dpi, fever 7 dpi | 2 euthanized at 7 dpi | Trachea (3) | 107 |
| Both groups – abnormal blood exudation, congestion and inflammation around trachea. More severe pathology in juvenile than aged. | |||||
| 6 euthanized at 15 dpi | |||||
| Juvenile - interstitial pneumonia, pulmonary fibrosis | |||||
| Aged – No interstitial pneumonia detected, but inflammation around trachea persisted | |||||
| 14 RM 14 M 8-12 mo | SARS-CoV-2-KMS1/2020IN | 14/14 Fever, -appetite and activity Clinically normal by 10 dpi | Euthanized: | Throat (2 – 14) | 142 |
| 2 NHP at 3 and 5 dpi | Nose – peaked at 2 and 5 dpi, shed until 27 dpi | ||||
| 3 NHP at 7 and 9 dpi | Rectum (9-27) | ||||
| 2 NHP at 21 dpi | Blood (5) | ||||
| 2 NHP not euthanized | |||||
| Gross: | |||||
| 12/12 Red lesions in lungs | |||||
| 1/2 Severe scattered pleural adhesions 5 dpi | |||||
| Histopathology: | |||||
| Patchy edema, mild to marked interstitial pneumonia, DAD |
§ RM rhesus macaque, F female, M male, † IT intratracheal, IN intranasal, PO per oral, CJ conjunctival, IV intravenous, IG intragastric, * dpi days postinfection, # CM cynomolgus macaque, DAD diffuse alveolar damage, vWF von Willebrand factor, ‡ AGM African green monkey, BALF bronchoalveolar lavage fluid.