scholarly journals Clinical and Histopathologic Features of a Feline SARS-CoV-2 Infection Model Are Analogous to Acute COVID-19 in Humans

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1550
Author(s):  
Jennifer M. Rudd ◽  
Miruthula Tamil Selvan ◽  
Shannon Cowan ◽  
Yun-Fan Kao ◽  
Cecily C. Midkiff ◽  
...  
Keyword(s):  
Animal Models ◽  
Diffuse Alveolar Damage ◽  
Significant Degree ◽  
Clinical Disease ◽  
Infection Model ◽  
Post Inoculation ◽  
Pulmonary Lesions ◽  
Viral Loads ◽  
Specific Pathogen ◽  
Feline Model

The emergence and ensuing dominance of COVID-19 on the world stage has emphasized the urgency of efficient animal models for the development of therapeutics for and assessment of immune responses to SARS-CoV-2 infection. Shortcomings of current animal models for SARS-CoV-2 include limited lower respiratory disease, divergence from clinical COVID-19 disease, and requirements for host genetic modifications to permit infection. In this study, n = 12 specific-pathogen-free domestic cats were infected intratracheally with SARS-CoV-2 to evaluate clinical disease, histopathologic lesions, and viral infection kinetics at 4 and 8 days post-inoculation; n = 6 sham-inoculated cats served as controls. Intratracheal inoculation of SARS-CoV-2 produced a significant degree of clinical disease (lethargy, fever, dyspnea, and dry cough) consistent with that observed in the early exudative phase of COVID-19. Pulmonary lesions such as diffuse alveolar damage, hyaline membrane formation, fibrin deposition, and proteinaceous exudates were also observed with SARS-CoV-2 infection, replicating lesions identified in people hospitalized with ARDS from COVID-19. A significant correlation was observed between the degree of clinical disease identified in infected cats and pulmonary lesions. Viral loads and ACE2 expression were also quantified in nasal turbinates, distal trachea, lungs, and other organs. Results of this study validate a feline model for SARS-CoV-2 infection that results in clinical disease and histopathologic lesions consistent with acute COVID-19 in humans, thus encouraging its use for future translational studies.

scholarly journals Clinicopathologic features of a feline SARS-CoV-2 infection model parallel acute COVID-19 in humans

2021 ◽  
Author(s):  
Jennifer Rudd ◽  
Miruthula Tamil Selvan ◽  
Shannon Cowan ◽  
Cecily Midkiff ◽  
Jerry Ritchey ◽  
...  
Keyword(s):  
Animal Models ◽  
Respiratory Disease ◽  
Diffuse Alveolar Damage ◽  
Significant Degree ◽  
Clinical Disease ◽  
Infection Model ◽  
Pulmonary Lesions ◽  
Viral Loads ◽  
Clinical Scoring ◽  
Feline Model

The emergence and ensuing dominance of COVID-19 on the world stage has emphasized the urgency of efficient animal models for the development of therapeutics and assessment of immune responses to SARS-CoV-2 infection. Shortcomings of current animal models for SARS-CoV-2 include limited lower respiratory disease, divergence from clinical COVID-19 disease, and requirements for host genetic modifications to permit infection. This study validates a feline model for SARS-CoV-2 infection that results in clinical disease and histopathologic lesions consistent with severe COVID-19 in humans. Intra-tracheal inoculation of concentrated SARS-CoV-2 caused infected cats to develop clinical disease consistent with that observed in the early exudative phase of COVID-19. A novel clinical scoring system for feline respiratory disease was developed and utilized, documenting a significant degree of lethargy, fever, dyspnea, and dry cough in infected cats. In addition, histopathologic pulmonary lesions such as diffuse alveolar damage, hyaline membrane formation, fibrin deposition, and proteinaceous exudates were observed due to SARS-CoV-2 infection, imitating lesions identified in people hospitalized with ARDS from COVID-19. A significant correlation exists between the degree of clinical disease identified in infected cats and pulmonary lesions. Viral loads and ACE2 expression were quantified in nasal turbinates, distal trachea, lung, and various other organs. Natural ACE2 expression, paired with clinicopathologic correlates between this feline model and human COVID-19, encourage use of this model for future translational studies.

scholarly journals Pathogenicity of an African swine fever virus strain isolated in Vietnam and alternative diagnostic specimens for early detection of viral infection

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hu Suk Lee ◽  
Vuong Nghia Bui ◽  
Duy Tung Dao ◽  
Ngoc Anh Bui ◽  
Thanh Duy Le ◽  
...  
Keyword(s):  
Early Detection ◽  
Oral Fluid ◽  
African Swine Fever Virus ◽  
Fluid Collection ◽  
Clinical Signs ◽  
African Swine Fever ◽  
Post Inoculation ◽  
Tissue Samples ◽  
Viral Loads ◽  
Specimen Collection

Abstract Background African swine fever (ASF), caused by the ASF virus (ASFV), was first reported in Vietnam in 2019 and spread rapidly thereafter. Better insights into ASFV characteristics and early detection by surveillance could help control its spread. However, the pathogenicity and methods for early detection of ASFV isolates from Vietnam have not been established. Therefore, we investigated the pathogenicity of ASFV and explored alternative sampling methods for early detection. Results Ten pigs were intramuscularly inoculated with an ASFV strain from Vietnam (titer, 103.5 HAD50/mL), and their temperature, clinical signs, and virus excretion patterns were recorded. In addition, herd and environmental samples were collected daily. The pigs died 5–8 days-post-inoculation (dpi), and the incubation period was 3.7 ± 0.5 dpi. ASFV genome was first detected in the blood (2.2 ± 0.8) and then in rectal (3.1 ± 0.7), nasal (3.2 ± 0.4), and oral (3.6 ± 0.7 dpi) swab samples. ASFV was detected in oral fluid samples collected using a chewed rope from 3 dpi. The liver showed the highest viral loads, and ear tissue also exhibited high viral loads among 11 tissues obtained from dead pigs. Overall, ASFV from Vietnam was classified as peracute to acute form. The rope-based oral fluid collection method could be useful for early ASFV detection and allows successful ASF surveillance in large pig farms. Furthermore, ear tissue samples might be a simple alternative specimen for diagnosing ASF infection in dead pigs. Conclusions Our data provide valuable insights into the characteristics of a typical ASFV strain isolated in Vietnam and suggest an alternative, non-invasive specimen collection strategy for early detection.

scholarly journals Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathrin Becker ◽  
Georg Beythien ◽  
Nicole de Buhr ◽  
Stephanie Stanelle-Bertram ◽  
Berfin Tuku ◽  
...  
Keyword(s):  
Animal Models ◽  
Syrian Hamster ◽  
Neutrophil Extracellular Traps ◽  
Virus Antigen ◽  
Endothelial Damage ◽  
Vascular Lesions ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Pulmonary Lesions ◽  
Extracellular Traps

Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed. SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models. Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients. Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans. Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far. Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19. Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi. Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations. In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi. Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis.

scholarly journals Comparative study of egg contamination with Salmonella Heidelberg and Salmonella Typhimurium

2019 ◽  
Vol 56 (1) ◽  
pp. e150479
Author(s):  
Germana Vizzotto Osowski ◽  
Lana Flávia Baron ◽  
Arlei Codebella ◽  
Francisco Noé Fonseca ◽  
Sandra Camile Almeida Mota ◽  
...  
Keyword(s):  
Bacterial Pathogen ◽  
Negative Control ◽  
Infection Model ◽  
Hostile Environment ◽  
Specific Pathogen Free ◽  
Foreign Markets ◽  
Serological Tests ◽  
Statistical Software ◽  
Bacterial Penetration ◽  
Specific Pathogen

Cases of salmonellosis in humans have been associated with consumption of eggs contaminated with this bacterial pathogen due to insufficient heat treatment. The most prevalent serotypes of Salmonella in Brazil include serotypes Enteritidis, Typhimurium, and Heidelberg. The first two serotypes are major causes for eggs to be withheld from sale and for recalls over Salmonella contamination concerns in both domestic and foreign markets. Eggs may be contaminated through transovarian infection (transovarial transmission) due to the presence of the microorganism in the hen’s oviduct and bacterial penetration of the eggshell. There is little data in the literature on the susceptibility of egg contamination and eggshell penetration by Brazilian serotypes of Salmonella. The present study aimed to evaluate the ability of S. Heidelberg and S. Typhimurium serotypes to penetrate through the eggshell and detect these bacteria in the albumen and yolk according to the thickness of the eggshell. SPF (specific-pathogen-free) eggs were artificially contaminated by contact with moist cotton containing Salmonella (15 x 108 CFU/ml). Eggs were divided into the following groups: negative control (not contaminated), S. Heidelberg, and S. Typhimurium. Subsequently, these eggs were incubated at 37°C, and their contents analyzed after 4 h and 24 h of incubation. The evaluation (assessment) of the contamination was performed by traditional bacteriology and confirmed by biochemical and serological tests. Treatments were compared with Fisher’s test using a SAS statistical software. For S. Heidelberg, the percentage of positivity (positive cases) was lower in both albumen and yolk at 4 h and 24 h intervals (33.33% and 3.7%, and 3.7% and 3.7%, respectively) compared to S. Typhimurium (26.63% and 7.41%, and 33.33% and 33.33%, respectively). These findings suggest that the former strain (S. Heidelberg) was unable to survive in the hostile environment of the albumen. In contrast, eggshell thickness had no significant correlation with the number of positive samples. In conclusion, the results obtained in the egg infection model show that the Salmonella strains tested were able to penetrate the eggshell and multiply in both the albumen and yolk and that S. Typhimurium proved to be the most efficient to grow within these portions of the egg.

scholarly journals Coxiella burnetii Intratracheal Aerosol Infection Model in Mice, Guinea Pigs, and Nonhuman Primates

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
A. E. Gregory ◽  
E. J. van Schaik ◽  
K. E. Russell-Lodrigue ◽  
A. P. Fratzke ◽  
J. E. Samuel
Keyword(s):  
Animal Models ◽  
Coxiella Burnetii ◽  
Guinea Pigs ◽  
Nonhuman Primates ◽  
Q Fever ◽  
Febrile Illness ◽  
Cell Vaccine ◽  
Infection Model ◽  
Atypical Pneumonia ◽  
Content Type

ABSTRACT Coxiella burnetii, the etiological agent of Q fever, is a Gram-negative bacterium transmitted to humans by inhalation of contaminated aerosols. Acute Q fever is often self-limiting, presenting as a febrile illness that can result in atypical pneumonia. In some cases, Q fever becomes chronic, leading to endocarditis that can be life threatening. The formalin-inactivated whole-cell vaccine (WCV) confers long-term protection but has significant side effects when administered to presensitized individuals. Designing new vaccines against C. burnetii remains a challenge and requires the use of clinically relevant modes of transmission in appropriate animal models. We have developed a safe and reproducible C. burnetii aerosol challenge in three different animal models to evaluate the effects of pulmonary acquired infection. Using a MicroSprayer aerosolizer, BL/6 mice and Hartley guinea pigs were infected intratracheally with C. burnetii Nine Mile phase I (NMI) and demonstrated susceptibility as determined by measuring bacterial growth in the lungs and subsequent dissemination to the spleen. Histological analysis of lung tissue showed significant pathology associated with disease, which was more severe in guinea pigs. Infection using large-particle aerosol (LPA) delivery was further confirmed in nonhuman primates, which developed fever and pneumonia. We also demonstrate that vaccinating mice and guinea pigs with WCV prior to LPA challenge is capable of eliciting protective immunity that significantly reduces splenomegaly and the bacterial burden in spleen and lung tissues. These data suggest that these models can have appreciable value in using the LPA delivery system to study pulmonary Q fever pathogenesis as well as designing vaccine countermeasures to C. burnetii aerosol transmission.

scholarly journals Feline Model of Acute Nipah Virus Infection and Protection with a Soluble Glycoprotein-Based Subunit Vaccine

2006 ◽  
Vol 80 (24) ◽  
pp. 12293-12302 ◽  
Author(s):  
Bruce A. Mungall ◽  
Deborah Middleton ◽  
Gary Crameri ◽  
John Bingham ◽  
Kim Halpin ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Case Reports ◽  
Mammalian Species ◽  
Nipah Virus ◽  
Disease Onset ◽  
Hendra Virus ◽  
Clinical Disease ◽  
Pcr Analysis ◽  
Wide Range ◽  
Feline Model

ABSTRACT Nipah virus (NiV) and Hendra virus (HeV) are paramyxoviruses capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. Case reports from outbreaks and previous challenge experiments have suggested that cats were highly susceptible to NiV infection, responding with a severe respiratory disease and systemic infection. Here we have assessed the cat as a model of experimental NiV infection and use it in the evaluation of a subunit vaccine comprised of soluble G glycoprotein (sG). Two groups of two adult cats each were inoculated subcutaneously with either 500 or 5,000 50% tissue culture infective dose(s) (TCID50) of NiV. Animals were monitored closely for disease onset, and extensive analysis was conducted on samples and tissues taken during infection and at necropsy to determine viral load and tissue tropism. All animals developed clinical disease 6 to 9 days postinfection, a finding consistent with previous observations. In a subsequent experiment, two cats were immunized with HeV sG and two were immunized with NiV sG. Homologous serum neutralizing titers were greater than 1:20,000, and heterologous titers were greater than 1:20,000 to 16-fold lower. Immunized animals and two additional naive controls were then challenged subcutaneously with 500 TCID50 of NiV. Naive animals developed clinical disease 6 to 13 days postinfection, whereas none of the immunized animals showed any sign of disease. TaqMan PCR analysis of samples from naive animals revealed considerable levels of NiV genome in a wide range of tissues, whereas the genome was evident in only two immunized cats in only four samples and well below the limit of accurate detection. These results indicate that the cat provides a consistent model for acute NiV infection and associated pathogenesis and an effective subunit vaccine strategy appears achievable.

scholarly journals Experimental Feline Infectious Enteritis in the Germfree Cat

1967 ◽  
Vol 4 (4) ◽  
pp. 391-410 ◽  
Author(s):  
M. W. Rohovsky ◽  
R. A. Griesemer
Keyword(s):  
Inclusion Body ◽  
Temperature Rise ◽  
Clinical Disease ◽  
Post Inoculation ◽  
Normal Range ◽  
Diagnostic Significance ◽  
Cell Hyperplasia ◽  
Macroscopic Lesion

In the absence of other microorganisms the virus of feline infectious enteritis produced a mild, non-fatal clinical disease in germfree cats. A biphasic temperature rise occurred on post inoculation day (PID) 2 and 4. All of the germfree cats began to recover by PID 7. Absolute lymphopenia occurred on the first day followed by absolute neutropenia on PID 4. The leucocyte counts were within the normal range by PID 10. Severe atrophy of the thymus was the only macroscopic lesion produced. Depletion of mature lymphocytes and reticuloendothelial cell hyperplasia occurred in all other lymphocytic tissue. No inclusion body considered to be of diagnostic significance could be demonstrated. There was no evidence of enteritis grossly or microscopically in germfree cats.

scholarly journals Histopathologic Findings and Energy Dispersive X-ray Spectroscopic Analysis of Experimentally Induced Foreign-body Pneumonias in Rats

1989 ◽  
Vol 26 (6) ◽  
pp. 479-487 ◽  
Author(s):  
R. F. Slocombe ◽  
M. G. Evans ◽  
F. J. Derksen
Keyword(s):  
Foreign Body ◽  
Alveolar Macrophages ◽  
Energy Dispersive Spectroscopy ◽  
Mineral Oil ◽  
Energy Dispersive ◽  
Post Inoculation ◽  
Diagnostic Features ◽  
Pulmonary Lesions ◽  
Microscopic Features

To document the diagnostic features of foreign-body pneumonias, four commonly used orally administered medicaments were instilled into the lungs of Sprague-Dawley rats. Rats in each group received a single 0.4 ml dose of either barium sulfate suspension (BaSO4), mineral oil, Pepto-bismol®, or Kaopectate® inoculated into a lung via a mainstem bronchus. The other lung served as a non-inoculated control. Rats were euthanatized on post-inoculation day 2 or 7 in order to document fully-developed, acute pulmonary lesions and developing, chronic pulmonary lesions, respectively. Light microscopic features of BaSO4-inoculated lungs were distinctive from changes in mineral oil-inoculated lungs at both post-inoculation days. On post-inoculation day 2, rats inoculated with BaSO4 had pneumonia characterized by large numbers of alveolar macrophages containing green-to-brown granular material. There was minimal interstitial involvement. On post-inoculation day 2, mineral oil caused pneumonia characterized by giant cells and alveolar macrophages that had cytoplasms distended with variably-sized clear vacuoles. Lungs inoculated with BaSO4 or mineral oil had changed little on post-inoculation day 7 compared to the light microscopic features observed on day 2. On post-inoculation day 2, rats inoculated with either Pepto-bismol® or Kaopectate® had broncho-interstitial pneumonia with areas of necrosis and hemorrhage. On post-inoculation day 7, lungs inoculated with Pepto-bismol® or Kaopectate® had extensive fibrosis within alveolar lumens. Energy dispersive spectroscopy performed on sections of lung from rats given BaSO4, Pepto-bismol®, and Kaopectate® yielded a unique elemental spectrum for each compound in situ on post-inoculation days 2 and 7. We conclude that pulmonary responses differ among these compounds and that energy dispersive spectroscopy is a useful diagnostic adjunct for the definitive identification of elements comprising BaSO4, Pepto-bismol®, and Kaopectate® in situ in affected lungs.

Sign in / Sign up

Export Citation Format

Share Document