Table 2.
Clinical Signs, Pulmonary and Extrapulmonary Pathology, and Viral Distribution in Spontaneous Animal Models of COVID-19
| Viral Replication and Tissue Tropism | Clinical Signs | Pulmonary Pathology | Extrapulmonary Pathology | Immunohistochemical Localization of SARS-CoV-2 |
|---|---|---|---|---|
| Rhesus macaque21,54,60,61 | ||||
| Viral RNA: Nasal wash, throat swabs, bronchoalveolar lavage, respiratory tissues, lymphoid tissue, and intestine Infectious virus: Bronchoalveolar lavage, shedding peaks in first few days, declines thereafter | Asymptomatic or fever, weight loss, occasional cough, reduced activity and appetite; peak within first week, resolution at 9-14 dpi; age enhanced disease | Gross pulmonary hemorrhage, radiographically evident interstitial pneumonia with diffuse alveolar damage | In some animals, lymphoid hyperplasia, pericardial effusion | Respiratory: Type I and II pneumocytes, alveolar macrophages; nasal and airway epithelium Intestine: lymphocytes and macrophages in lamina propria |
| Cynomologus macaque21,55,62 | ||||
| Viral RNA: Abundant nasal shedding by 2 dpi (and up to 21 dpi), intermittent throat shedding, rare fecal shedding; no virus detectable in blood | Asymptomatic or fever, weight loss in first week dpi; no age enhanced disease | Acute or proliferative advanced diffuse alveolar damage with epithelial syncitia; serial CT reveals ground-glass opacities, reticulation, paving, or alveolar consolidation | No | Respiratory: Type I and II pneumocytes, ciliated epithelial cells of airways and nasal mucosa |
| African Green monkeys66 | ||||
| Viral RNA: Nasal, bronchoalveolar lavage, oral and rectal swabs from 2–3 dpi, absent from blood; shedding persisted for 15 (nasal) to 21 (rectal) d | No overt clinical signs, reduced appetite | Diffuse alveolar damage and interstitial pneumonia with hyaline membrane formation, type II pneumocyte hyperplasia, pulmonary edema, and hemorrhage | No | Respiratory: Type I and II pneumocytes, bronchial epithelial cells |
| Common marmoset21 | ||||
| Viral RNA: Nasal, low levels, 2 wk dpi | None | Very mild interstitial mononuclear infiltration | No | Not done |
| Ferret74,75 | ||||
| Viral RNA: Nasal, low copy numbers in rectal swabs; nasal turbinate, soft palate, tonsils; absent in lung Infectious virus: Nasal washes only | Rare clinical signs of fever, weight loss, and inappetance 10 and 12 dpi | Interstitial pneumonia with hyaline membrane formation, type II pneumocyte hyperplasia, lymphoplasmacytic perivasculitis and vasculitis | No | Respiratory: epithelial cells nasal turbinate, trachea, pulmonary interstitum Intestinal: intestinal lamina propria |
| Mink63,76,77 | ||||
| Viral RNA: Conchae, lung, throat, and rectal swabs, rare liver and intestine | Respiratory signs, anorexia, death | Diffuse alveolar damage and interstitial pneumonia with hyaline membrane formation | No | Respiratory: epithelial cells nasal turbinate, trachea, pulmonary epithelium, macrophages |
| Syrian hamster18,67–69,71 | ||||
| Viral RNA: Nasal turbinates, trachea, lungs (high), intestine (mid), salivary glands, heart, liver, spleen, lymph nodes, kidney, brain, blood (low) up to 7 dpi Infectious virus: Lung up to 4 dpi | Hunched, lethargic, rapid breathing, piloerection, weight loss in first week; age enhanced disease | Rhinitis, tracheitis, diffuse alveolar destruction, hyaline membrane formation, marked mononuclear cell infiltration; consolidation and hemorrhage, syncitia, peak at 4 dpi | Intestinal: necrosis, damaged and lamina propria mononuclear cell infiltration at 4 dpi Spleen: white pulp atrophy and apoptosis (2–4 dpi) followed by lymphoid hyperplasia (7 dpi) Heart: myofiber degeneration and interstitial edema | Respiratory: bronchiolar epithelial cells, alveolar macrophages, and type I and II pneumocyte, Intestinal: enterocytes |
| Deer mouse73 | ||||
| Viral RNA: Lungs, up to 14 dpi Infectious virus: Lungs, 3 and 6 dpi |
No clinical signs | 3 dpi: broncho-interstitial pneumonia and leucocytoclastic vasculitis, multinucleate epithelial cells, fibrinopurulent rhinitis and sinusitis | CNS: neutrophilic infiltration of afferent ethmoidal, olfactory, maxillary, and other sensory nerves; frontal cortical encephalitis, gliosis, and immunoreactivity for SARS-CoV-2 in brainstem nuclei is evident | Nasal: sustentacular, olfactory, basal cells Tongue: mucosal epithelium CNS: sensory ganglia, olfactory bulb, brain, microglia Eye: retinal ganglion cells, inner nuclear layer Intestinal: crypt epithelium, lamina propria, macrophages, ileum and duodenum |
| Cat22 | ||||
| Viral RNA: nasal turbinate, soft palate, tonsil, trachea, lungs, small intestine, rarely rectal, up to 12 dpi Infectious virus: nasal turbinates, soft palates, tonsils, tracheas, lungs up to 6 dpi |
No clinical signs | 3 dpi: massive lesions in nasal and tracheal mucosa, and lungs | No | Not done |
| Dog22 | ||||
| Viral RNA: intermittent rare rectal, up to 6 dpi Infectious virus: none |
No studies to date | No studies to date | No studies to date | No studies to date |
Abbreviations, CT: Computed tomography, Dpi: days post-infection, RNA: ribonucleic acid