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 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 Influenza C and D viral load in cattle correlates with bovine respiratory disease (BRD): Emerging role of orthomyxoviruses in the pathogenesis of BRD

2020 ◽  
Author(s):  
Ruth H. Nissly ◽  
Noriza Zaman ◽  
Puteri Ainaa S. Ibrahim ◽  
Kaitlin McDaniel ◽  
Levina Lim ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Geometric Mean ◽  
Bovine Respiratory Disease ◽  
The United States ◽  
Influenza Viruses ◽  
Cattle Industry ◽  
Diarrhea Virus ◽  
Viral Loads ◽  
Influenza C Virus ◽  
Syncytial Virus

AbstractBovine respiratory disease (BRD) is the costliest disease affecting the cattle industry globally. Despite decades of research, the pathophysiology of BRD is not yet fully understood. It is widely believed that viruses predispose cattle to bacterial infection by causing direct damage to the respiratory tract and interfering with the immune system, leading to bacterial pneumonia. BRD remains a major challenge despite extensive vaccination against all major viral pathogens associated with the disease. Orthomyxoviruses (Influenza C & D viruses), have recently been found to infect cattle throughout the United States and are implicated to play a role in BRD. Here, we use the largest cohort study to date to investigate the association of influenza viruses in cattle with BRD. Cattle (n=599) from 3 locations were individually observed and scored for respiratory symptoms using the McGuirk scoring system. Deep pharyngeal and mid-nasal swabs were collected from each animal and were tested quantitatively for bovine viral diarrhea virus, bovine herpesvirus 1, bovine respiratory syncytial virus, bovine coronavirus, influenza C virus (ICV) and influenza D virus (IDV) by real-time PCR. Cattle that have higher viral loads of IDV and ICV also have greater numbers of co-infecting viruses than controls. More strikingly, in BRD-symptomatic cattle, the geometric mean of detectable IDV viral RNA was nearly 2 logs higher in co-infected animals (1.30×104) than those singly infected with IDV (2.19×102). This is strong evidence that viral coinfections can lead to higher replication of IDV. Our results strongly suggest that orthomyxoviruses may be significant contributors to BRD.

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.

Efficacy, Mechanism, and Safety of Herbal Medicine for Respiratory Disease Induced by Particulate Matter: a Protocol for a Scoping Review

2021 ◽  
Author(s):  
Jungtae Leem ◽  
Yohwan Kim ◽  
Kwan-Il Kim
Keyword(s):  
Particulate Matter ◽  
Animal Models ◽  
Respiratory Disease ◽  
Scoping Review ◽  
Respiratory Diseases ◽  
English Language ◽  
Herbal Medicines ◽  
Cochrane Central Register

Abstract Background: Particulate matter (PM) is an important environmental risk factor in the initiation and exacerbation of respiratory disease. Various herbal medicines have exhibited a reduction in symptoms of respiratory diseases induced by PM in animal models; however, their efficacy, mechanism, and safety have not been reviewed. This review will evaluate the efficacy, safety, and mechanism of action of herbal medicines in respiratory diseases caused by PM. Methods:We will follow the scoping review framework developed by Arksey and O’Malley. MEDLINE (via PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials will be searched for relevant English-language publications, and only peer-reviewed, controlled comparative in-vivo/in-vitro studies examining the effects of herbs in animal models of respiratory disease induced by PM will be included. The basic characteristics, research method, possible mechanism, and results will be extracted. The primary outcome will be pulmonary function; secondary outcomes will be inflammatory markers, reactive oxygen species, histology and mechanisms, and adverse events. Two researchers will independently perform the study selection, data extraction, and quality assessment. RevMan software (version 5.3) will be used for the quantitative data synthesis. When appropriate, data will be pooled for meta-analysis using fixed or random effects models; otherwise, evidence will be summarized qualitatively. Ethics and Dissemination: Ethical approval is not required because individual patient data will not be included. The findings will be disseminated through peer-reviewed publications or conference presentations.Registration number: This review protocol has been registered with the Open Science Framework on February 12, 2021 (https://osf.io/s7uvk/)

scholarly journals PSVI-24 Evolution and risk factors of pulmonary lesions evaluated with thoracic ultrasonography in pre-weaned beef calves at arrival at the rearing facilities

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 208-209
Author(s):  
Carolina Tejero ◽  
Maria Devant ◽  
Joan Pujols ◽  
Sonia Marti
Keyword(s):  
Risk Factors ◽  
Respiratory Disease ◽  
Mixed Effects ◽  
Mixed Effects Models ◽  
Beef Calves ◽  
Pulmonary Lesions ◽  
Current Health ◽  
D 12 ◽  
Over Time ◽  
Transport Type

Abstract Bovine respiratory disease (BRD) is one of the main health problems in in pre-weaning calves at rearing farms. The aim of this study was to evaluate the evolution of pulmonary lesions using a thoracic ultrasonography and its association with predictable risk factors. Thoracic ultrasonography was performed in 811 calves (45–56 kg of BW and 3–4 wk of age) on 5 different rearing facilities at arrival and from d 12 to d 27 after arrival. Thoracic ultrasonography score was classified based on Adams and Buczinski (2016). Weight (light vs heavy), breed (dairy vs crossbred), source (national vs international), season, and number of calves arriving at the facility were recorded and used to evaluate risk factors. Data were analyzed using mixed effects models. At arrival 31% of the calvespresented pulmonary lesions, 21% were mild and 10% severe. After 12–27 d the number of calves without lesion decreased (P < 0.001; 70.3 ± 3.93% vs 34.0 ± 3.93%), number of severe lesions increased (P < 0.001; 8.9% ± 4.78% vs 40.1% ± 4.78%), however mild lesions were constant over time. Percentage of severe pulmonary lesions were greater (P < 0.001) when calves arrived in fall than spring, summer and winter; when calf source (P < 0.001) was international than national; and when their breeds (P < 0.001) were crossbred than dairy. A tendency (P = 0.09) was observed with the increase of severe pulmonary lesions with an increase of animals received by batch. At arrival, calves already had pulmonary lesions that increased in severity over time, therefore current health protocols do not mitigate BRD and more attention should be taken on risk factors such as breed, transport type and season.

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 Comparative Analysis of Plant and Animal Models for Characterization of Burkholderia cepacia Virulence

2003 ◽  
Vol 71 (9) ◽  
pp. 5306-5313 ◽  
Author(s):  
Steve P. Bernier ◽  
Laura Silo-Suh ◽  
Donald E. Woods ◽  
Dennis E. Ohman ◽  
Pamela A. Sokol
Keyword(s):  
Comparative Analysis ◽  
Animal Models ◽  
Burkholderia Cepacia ◽  
Parent Strain ◽  
Lung Infection ◽  
Infection Model ◽  
Burkholderia Multivorans ◽  
Lung Infections

ABSTRACT A simple alfalfa model was developed as an alternative infection model for virulence studies of the Burkholderia cepacia complex. Symptoms of disease were observed in wounded alfalfa seedlings within 7 days following inoculation of 101 to 105 CFU of most strains of the B. cepacia complex. Strains from seven genomovars of the B. cepacia complex were tested for virulence in the alfalfa model, and the degree of virulence was generally similar in strains belonging to the same genomovar. Strains of Burkholderia multivorans and some strains of Burkholderia stabilis did not cause symptoms of disease in alfalfa seedlings. Representative strains were also tested for virulence using the rat agar bead model. Most of the strains tested were able to establish chronic lung infections; B. stabilis strains were the exception. Most of the strains that were virulent in the alfalfa infection model were also virulent in the lung infection model. The B. cepacia genomovar III mutants K56pvdA::tp and K56-H15 were significantly less virulent in the alfalfa infection model than their parent strain. Therefore, this alfalfa infection model may be a useful tool for assessing virulence of strains of the B. cepacia complex and identifying new virulence-associated genes.

Sign in / Sign up

Export Citation Format

Share Document