Nonhuman primate (NHP) models will expedite therapeutics and vaccines for COVID-19 into clinical trials. We compared acute SARS-CoV-2 infection in young and old rhesus macaques and baboons and old marmosets. Macaques had clinical signs of viral infection, mild-to-moderate pneumonitis and extra-pulmonary pathologies; both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage (BAL) was increased in old versus young baboons. Using techniques like CT imaging, immunophenotyping, alveolar/peripheral cytokine responses and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent Type I-interferon response. Macaques developed T cell memory phenotype/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.

Objective: To estimate the relative accuracy of a thoracic focused assessment with sonography for trauma (TFAST) protocol for rapid diagnosis of pneumothorax (PTX) and other thoracic injury in traumatized dogs. Design: Prospective case series. Setting: Private veterinary emergency center. Animals: One hundred and forty-five client-owned dogs evaluated within 24-hours of injury. Interventions: Thoracic focused assessment with sonography for trauma protocol. Measurements and Main Results: Traumatized dogs were evaluated with a conventional ultrasound (US) machine using a standardized 4-point thoracic FAST protocol before thoracic radiography (CXR) and thoracocentesis. PTX was diagnosed by the absence of the 'glide sign,' defined as the lack of the normal dynamic interface between lung margins gliding along the thoracic wall during respiration. Concurrent thoracic trauma was diagnosed by the presence of pleural or pericardial fluid or the presence of a 'step sign,' defined as an abnormal glide sign. Accuracy of TFAST was calculated relative to CXR findings. Results: Overall sensitivity (Se), specificity (Sp), and accuracy of TFAST relative to CXR were 78.1% (95% CI; 61.5, 89.9), 93.4% (95% CI; 87.4, 97.1), and 90.0%, respectively. Se and Sp were higher in dogs with penetrating trauma (93.3%, 96.0%) and for the evaluator with the most clinical experience (95.2%, 96.0%); only Se between the most experienced compared with others was statistically significant (Po0.05). TFAST documented other concurrent thoracic injury. Median time for TFAST was 3 minutes. Conclusions and Clinical Relevance: TFAST has the potential to rapidly diagnose PTX and other thoracic injury and guide therapy, including potentially life-saving interventions, in traumatized dogs.

In humans the dural tail is a sign seen on contrast enhanced T1 weighted magnetic resonance images. This finding is considered specific for meningioma. The purpose of this study was to determine how often the dural tail occurs in cats and dogs and whether it is a specific sign for meningiomas in these species. MR examinations for eighteen dogs and four cats with proven diagnoses were reviewed. Diagnoses included ten meningiomas (seven dogs and three cats), three gliomas, two pituitary tumors, single examples of two other tumor types and five patients with mass lesions due to inflammatory disease. Contrast enhanced T1 weighted images were evaluated independently by three of the authors for the presence of a dural tail, without knowledge of the diagnoses. The results were compared to the diagnosis for each patient and the performance of individual reviewers compared. When their results were averaged, the reviewers reported the presence of a dural tail in 6 of 10 (60%) meningiomas, although detection varied between observers from 40% to 80%. Each reviewer had one false positive result, two reported a dural tail with a chromophobe adenocarcinoma and one with a toxoplasma meningoencephalitis. When a dural tail is seen an associated mass is most likely a meningioma. It is uncertain whether the dural tail represents neoplastic infiltration beyond the margins of the meningioma. This should be considered when planning treatment.

SummaryThere are no known cures or vaccines for COVID-19, the defining pandemic of this era. Animal models are essential to fast track new interventions and nonhuman primate (NHP) models of other infectious diseases have proven extremely valuable. Here we compare SARS-CoV-2 infection in three species of experimentally infected NHPs (rhesus macaques, baboons, and marmosets). During the first 3 days, macaques developed clinical signatures of viral infection and systemic inflammation, coupled with early evidence of viral replication and mild-to-moderate interstitial and alveolar pneumonitis, as well as extra-pulmonary pathologies. Cone-beam CT scans showed evidence of moderate pneumonia, which progressed over 3 days. Longitudinal studies showed that while both young and old macaques developed early signs of COVID-19, both groups recovered within a two-week period. Recovery was characterized by low-levels of viral persistence in the lung, suggesting mechanisms by which individuals with compromised immune systems may be susceptible to prolonged and progressive COVID-19. The lung compartment contained a complex early inflammatory milieu with an influx of innate and adaptive immune cells, particularly interstitial macrophages, neutrophils and plasmacytoid dendritic cells, and a prominent Type I-interferon response. While macaques developed moderate disease, baboons exhibited prolonged shedding of virus and extensive pathology following infection; and marmosets demonstrated a milder form of infection. These results showcase in critical detail, the robust early cellular immune responses to SARS-CoV-2 infection, which are not sterilizing and likely impact development of antibody responses. Thus, various NHP genera recapitulate heterogeneous progression of COVID-19. Rhesus macaques and baboons develop different, quantifiable disease attributes making them immediately available essential models to test new vaccines and therapies.

OBJECTIVE To estimate reliability of interpretation of neurologic examination findings for localization of vestibular dysfunction in dogs. DESIGN Cross-sectional study. ANIMALS 496 dogs that underwent MRI of the head for diagnosis of a neurologic problem between September 2011 and September 2015. PROCEDURES Medical records were reviewed and data collected regarding signalment and neurologic examination, MRI, and CSF findings. Independent observers interpreted the findings, and agreement was assessed for a subset of dogs. Distributions of variables were compared between dogs with and without a neurologic findings-based interpretation of vestibular disease. RESULTS 37% (185/496) of dogs had signs of vestibular dysfunction, of which 82% (151/185) had MRI abnormalities. In 73% (110/151) of dogs with MRI abnormalities, lesions involved central vestibular structures, and in 19% (29/151), lesions involved peripheral vestibular structures. On the basis of neurologic findings interpretation, 86% (160/185) of dogs were classified as having central vestibular dysfunction, and 61% (98/160) of these had an MRI-identified central vestibular lesion. Agreement among 3 independent observers was good (κ = 0.72) regarding use of neurologic examination findings to diagnose central versus peripheral vestibular dysfunction and very good (κ = 0.85) regarding use of MRI to diagnose peripheral vestibular lesions. Despite this agreement, only 29% (7/24) of dogs with a consensus clinical interpretation of peripheral vestibular dysfunction had MRI-identified peripheral lesions. CONCLUSIONS AND CLINICAL RELEVANCE Although interobserver agreement was good for distinguishing central from peripheral vestibular dysfunction in dogs through interpretation of neurologic examination findings, this interpretation did not agree with the MRI-based diagnosis.