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1.
Viruses ; 12(6)2020 06 24.
Article in English | MEDLINE | ID: covidwho-620517

ABSTRACT

The respiratory Influenza A Viruses (IAVs) and emerging zoonotic viruses such as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pose a significant threat to human health. To accelerate our understanding of the host-pathogen response to respiratory viruses, the use of more complex in vitro systems such as normal human bronchial epithelial (NHBE) cell culture models has gained prominence as an alternative to animal models. NHBE cells were differentiated under air-liquid interface (ALI) conditions to form an in vitro pseudostratified epithelium. The responses of well-differentiated (wd) NHBE cells were examined following infection with the 2009 pandemic Influenza A/H1N1pdm09 strain or following challenge with the dsRNA mimic, poly(I:C). At 30 h postinfection with H1N1pdm09, the integrity of the airway epithelium was severely impaired and apical junction complex damage was exhibited by the disassembly of zona occludens-1 (ZO-1) from the cell cytoskeleton. wdNHBE cells produced an innate immune response to IAV-infection with increased transcription of pro- and anti-inflammatory cytokines and chemokines and the antiviral viperin but reduced expression of the mucin-encoding MUC5B, which may impair mucociliary clearance. Poly(I:C) produced similar responses to IAV, with the exception of MUC5B expression which was more than 3-fold higher than for control cells. This study demonstrates that wdNHBE cells are an appropriate ex-vivo model system to investigate the pathogenesis of respiratory viruses.


Subject(s)
Influenza A Virus, H1N1 Subtype/physiology , Influenza, Human/virology , Respiratory Mucosa/cytology , Respiratory Mucosa/virology , Animals , Bronchi/cytology , Bronchi/virology , Cells, Cultured , Chemokines/metabolism , Cytokines/metabolism , Dogs , Host-Pathogen Interactions , Humans , Immunity, Innate , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/epidemiology , Intercellular Junctions , Madin Darby Canine Kidney Cells , Models, Biological , Mucin 5AC/metabolism , Pandemics , Virus Cultivation
2.
Viruses ; 12(9)2020 09 01.
Article in English | MEDLINE | ID: covidwho-742847

ABSTRACT

Until vaccines and effective therapeutics become available, the practical solution to transit safely out of the current coronavirus disease 19 (CoVID-19) lockdown may include the implementation of an effective testing, tracing and tracking system. However, this requires a reliable and clinically validated diagnostic platform for the sensitive and specific identification of SARS-CoV-2. Here, we report on the development of a de novo, high-resolution and comparative genomics guided reverse-transcribed loop-mediated isothermal amplification (LAMP) assay. To further enhance the assay performance and to remove any subjectivity associated with operator interpretation of results, we engineered a novel hand-held smart diagnostic device. The robust diagnostic device was further furnished with automated image acquisition and processing algorithms and the collated data was processed through artificial intelligence (AI) pipelines to further reduce the assay run time and the subjectivity of the colorimetric LAMP detection. This advanced AI algorithm-implemented LAMP (ai-LAMP) assay, targeting the RNA-dependent RNA polymerase gene, showed high analytical sensitivity and specificity for SARS-CoV-2. A total of ~200 coronavirus disease (CoVID-19)-suspected NHS patient samples were tested using the platform and it was shown to be reliable, highly specific and significantly more sensitive than the current gold standard qRT-PCR. Therefore, this system could provide an efficient and cost-effective platform to detect SARS-CoV-2 in resource-limited laboratories.


Subject(s)
Artificial Intelligence , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Pneumonia, Viral/virology , Animals , Chlorocebus aethiops , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Dogs , Humans , Madin Darby Canine Kidney Cells , Pandemics , Pneumonia, Viral/diagnosis , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Vero Cells
3.
Vet Microbiol ; 247: 108777, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-733593

ABSTRACT

Coronaviruses (CoVs) cause disease in a range of agricultural and companion animal species, and can be important causes of zoonotic infections. In humans, several coronaviruses circulate seasonally. Recently, a novel zoonotic CoV named SARS-CoV-2 emerged from a bat reservoir, resulting in the COVID-19 pandemic. With a focus on felines, we review here the evidence for SARS-CoV-2 infection in cats, ferrets and dogs, describe the relationship between SARS-CoV-2 and the natural coronaviruses known to infect these species, and provide a rationale for the relative susceptibility of these species to SARS-CoV-2 through comparative analysis of the ACE-2 receptor.


Subject(s)
Cat Diseases/virology , Coronavirus Infections/veterinary , Dog Diseases/virology , Evolution, Molecular , Pandemics/veterinary , Pneumonia, Viral/veterinary , Zoonoses/transmission , Animals , Betacoronavirus , Cats/virology , Dogs/virology , Ferrets/virology , Humans , Peptidyl-Dipeptidase A/metabolism , Receptors, Virus/genetics , Zoonoses/virology
4.
Open Vet J ; 10(2): 164-177, 2020 08.
Article in English | MEDLINE | ID: covidwho-724486

ABSTRACT

Viruses are having great time as they seem to have bogged humans down. Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and novel coronavirus (COVID-19) are the three major coronaviruses of present-day global human and animal health concern. COVID-19 caused by SARS-CoV-2 is identified as the newest disease, presumably of bat origin. Different theories on the evolution of viruses are in circulation, yet there is no denying the fact that the animal source is the skeleton. The whole world is witnessing the terror of the COVID-19 pandemic that is following the same path of SARS and MERS, and seems to be more severe. In addition to humans, several species of animals are reported to have been infected with these life-threatening viruses. The possible routes of transmission and their zoonotic potentialities are the subjects of intense research. This review article aims to overview the link of all these three deadly coronaviruses among animals along with their phylogenic evolution and cross-species transmission. This is essential since animals as pets or food are said to pose some risk, and their better understanding is a must in order to prepare a possible plan for future havoc in both human and animal health. Although COVID-19 is causing a human health hazard globally, its reporting in animals are limited compared to SARS and MERS. Non-human primates and carnivores are most susceptible to SARS-coronavirus and SARS-CoV-2, respectively, whereas the dromedary camel is susceptible to MERS-coronavirus. Phylogenetically, the trio viruses are reported to have originated from bats and have special capacity to undergo mutation and genomic recombination in order to infect humans through its reservoir or replication host. However, it is difficult to analyze how the genomic pattern of coronaviruses occurs. Thus, increased possibility of new virus-variants infecting humans and animals in the upcoming days seems to be the biggest challenge for the future of the world. One health approach is portrayed as our best way ahead, and understanding the animal dimension will go a long way in formulating such preparedness plans.


Subject(s)
Betacoronavirus/classification , Coronavirus Infections/veterinary , Middle East Respiratory Syndrome Coronavirus/classification , Pandemics/veterinary , Pneumonia, Viral/veterinary , SARS Virus/classification , Severe Acute Respiratory Syndrome/veterinary , Animals , Animals, Wild , Betacoronavirus/genetics , Camelids, New World/virology , Camelus/virology , Cats , Chiroptera/virology , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Disease Susceptibility/veterinary , Dogs , Eutheria/virology , Ferrets/virology , Humans , Lions/virology , Middle East Respiratory Syndrome Coronavirus/genetics , Phylogeny , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Primates/virology , Raccoon Dogs/virology , SARS Virus/genetics , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/transmission , Snakes/virology , Tigers/virology , Viverridae/virology
7.
Cell Rep ; 32(6): 108016, 2020 08 11.
Article in English | MEDLINE | ID: covidwho-670926

ABSTRACT

The influenza virus hemagglutinin (HA) and coronavirus spike (S) protein mediate virus entry. HA and S proteins are heavily glycosylated, making them potential targets for carbohydrate binding agents such as lectins. Here, we show that the lectin FRIL, isolated from hyacinth beans (Lablab purpureus), has anti-influenza and anti-SARS-CoV-2 activity. FRIL can neutralize 11 representative human and avian influenza strains at low nanomolar concentrations, and intranasal administration of FRIL is protective against lethal H1N1 infection in mice. FRIL binds preferentially to complex-type N-glycans and neutralizes viruses that possess complex-type N-glycans on their envelopes. As a homotetramer, FRIL is capable of aggregating influenza particles through multivalent binding and trapping influenza virions in cytoplasmic late endosomes, preventing their nuclear entry. Remarkably, FRIL also effectively neutralizes SARS-CoV-2, preventing viral protein production and cytopathic effect in host cells. These findings suggest a potential application of FRIL for the prevention and/or treatment of influenza and COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Fabaceae/chemistry , Orthomyxoviridae Infections/drug therapy , Plant Lectins/therapeutic use , Pneumonia, Viral/drug therapy , A549 Cells , Administration, Intranasal , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Chick Embryo , Chlorocebus aethiops , Dogs , Female , Humans , Influenza A Virus, H1N1 Subtype/drug effects , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred BALB C , Pandemics , Plant Lectins/administration & dosage , Plant Lectins/pharmacology , Protein Binding , Vero Cells , Viral Envelope Proteins/metabolism
8.
BMC Infect Dis ; 20(1): 536, 2020 Jul 23.
Article in English | MEDLINE | ID: covidwho-670669

ABSTRACT

BACKGROUND: As the COVID-19 pandemic continues to spread, early, ideally real-time, identification of SARS-CoV-2 infected individuals is pivotal in interrupting infection chains. Volatile organic compounds produced during respiratory infections can cause specific scent imprints, which can be detected by trained dogs with a high rate of precision. METHODS: Eight detection dogs were trained for 1 week to detect saliva or tracheobronchial secretions of SARS-CoV-2 infected patients in a randomised, double-blinded and controlled study. RESULTS: The dogs were able to discriminate between samples of infected (positive) and non-infected (negative) individuals with average diagnostic sensitivity of 82.63% (95% confidence interval [CI]: 82.02-83.24%) and specificity of 96.35% (95% CI: 96.31-96.39%). During the presentation of 1012 randomised samples, the dogs achieved an overall average detection rate of 94% (±3.4%) with 157 correct indications of positive, 792 correct rejections of negative, 33 incorrect indications of negative or incorrect rejections of 30 positive sample presentations. CONCLUSIONS: These preliminary findings indicate that trained detection dogs can identify respiratory secretion samples from hospitalised and clinically diseased SARS-CoV-2 infected individuals by discriminating between samples from SARS-CoV-2 infected patients and negative controls. This data may form the basis for the reliable screening method of SARS-CoV-2 infected people.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Mass Screening/methods , Odorants/analysis , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Animals , Bronchi/chemistry , Bronchi/virology , Case-Control Studies , Dogs , Double-Blind Method , Humans , Pandemics/prevention & control , Pilot Projects , Saliva/chemistry , Saliva/virology , Sensitivity and Specificity
9.
J Virol ; 94(15)2020 07 16.
Article in English | MEDLINE | ID: covidwho-661225

ABSTRACT

The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptors allows the definition of residues important for binding. From the 20 amino acids in ACE2 that contact S, up to 7 can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or acquisition of N-glycosylation sites located near the S interface. Of note, pigs and dogs, which are not infected or are not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with that from bat coronavirus strain RaTG13 (Bat-CoV-RaTG13) and pangolin coronavirus (Pangolin-CoV) strain hCoV-19/pangolin/Guangdong/1/2019 revealed that the latter contains only one substitution, whereas Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibits seven changes relative to human ACE2, and a similar number of substitutions is present in ACE2 of bats, raccoon dogs, and civets, suggesting that SARS-CoV-2 may not be especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2.IMPORTANCE SARS-CoV-2 is threatening people worldwide, and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear, and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes, indicating that the species barrier might be low. Exceptions are dogs and especially pigs, which revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/metabolism , Virus Attachment , Animals , Animals, Domestic , Betacoronavirus/metabolism , Chiroptera/virology , Coronavirus Infections/metabolism , Dogs , Glycosylation , Host-Pathogen Interactions , Humans , Models, Animal , Pandemics , Pets , Pneumonia, Viral/metabolism , Protein Binding , Protein Conformation , Protein Interaction Domains and Motifs , Raccoons/virology , Sequence Alignment , Sequence Analysis, Protein , Swine , Viverridae/virology
10.
Cell ; 182(5): 1284-1294.e9, 2020 09 03.
Article in English | MEDLINE | ID: covidwho-652603

ABSTRACT

The spike protein of SARS-CoV-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here, we investigated 80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious, but variants including A475V, L452R, V483A, and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious, whereas deletion of both N331 and N343 glycosylation drastically reduced infectivity, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in the development of vaccine and therapeutic antibodies.


Subject(s)
Antigens, Viral/genetics , Betacoronavirus/pathogenicity , Mutation , Spike Glycoprotein, Coronavirus/genetics , A549 Cells , Animals , Antigens, Viral/immunology , Betacoronavirus/genetics , Betacoronavirus/immunology , Binding Sites , Cattle , Chlorocebus aethiops , Cricetinae , Dogs , Glycosylation , HEK293 Cells , HeLa Cells , Humans , Macaca mulatta , Madin Darby Canine Kidney Cells , Mice , RAW 264.7 Cells , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Swine , Vero Cells , Virulence/genetics
11.
Euro Surveill ; 25(25)2020 06.
Article in English | MEDLINE | ID: covidwho-649992

ABSTRACT

The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen's eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.


Subject(s)
Chickens/immunology , Coronavirus/physiology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Madin Darby Canine Kidney Cells , Receptors, Virus/metabolism , Virus Cultivation/methods , Virus Replication , Animals , Betacoronavirus , Cell Line , Chickens/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Dogs , Eggs , Humans , Pandemics , Pneumonia, Viral , Severe Acute Respiratory Syndrome
12.
Mol Biol Evol ; 37(9): 2706-2710, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-641314

ABSTRACT

Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans. Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures. However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong. Here, we dispute the conclusions of Xia (2020. Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol. doi:10.1093/molbev/masa095) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor. We highlight major flaws in Xia's inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts. Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited.


Subject(s)
Alphacoronavirus/genetics , Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Genome, Viral , Pandemics , Pneumonia, Viral/epidemiology , Reassortant Viruses/genetics , Alphacoronavirus/classification , Alphacoronavirus/pathogenicity , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Biological Evolution , Chiroptera/virology , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Coronavirus Infections/virology , CpG Islands , Dogs , Eutheria/virology , Humans , Immune Evasion/genetics , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Protein Binding , RNA, Viral/genetics , RNA, Viral/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/immunology , RNA-Binding Proteins/metabolism , Reassortant Viruses/classification , Reassortant Viruses/pathogenicity , Virus Replication
13.
Euro Surveill ; 25(25)2020 06.
Article in English | MEDLINE | ID: covidwho-615420

ABSTRACT

The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen's eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.


Subject(s)
Chickens/immunology , Coronavirus/physiology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Madin Darby Canine Kidney Cells , Receptors, Virus/metabolism , Virus Cultivation/methods , Virus Replication , Animals , Betacoronavirus , Cell Line , Chickens/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Dogs , Eggs , Humans , Pandemics , Pneumonia, Viral , Severe Acute Respiratory Syndrome
14.
Vet Microbiol ; 247: 108777, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-611218

ABSTRACT

Coronaviruses (CoVs) cause disease in a range of agricultural and companion animal species, and can be important causes of zoonotic infections. In humans, several coronaviruses circulate seasonally. Recently, a novel zoonotic CoV named SARS-CoV-2 emerged from a bat reservoir, resulting in the COVID-19 pandemic. With a focus on felines, we review here the evidence for SARS-CoV-2 infection in cats, ferrets and dogs, describe the relationship between SARS-CoV-2 and the natural coronaviruses known to infect these species, and provide a rationale for the relative susceptibility of these species to SARS-CoV-2 through comparative analysis of the ACE-2 receptor.


Subject(s)
Cat Diseases/virology , Coronavirus Infections/veterinary , Dog Diseases/virology , Evolution, Molecular , Pandemics/veterinary , Pneumonia, Viral/veterinary , Zoonoses/transmission , Animals , Betacoronavirus , Cats/virology , Dogs/virology , Ferrets/virology , Humans , Peptidyl-Dipeptidase A/metabolism , Receptors, Virus/genetics , Zoonoses/virology
16.
Vaccine ; 38(33): 5123-5130, 2020 07 14.
Article in English | MEDLINE | ID: covidwho-592011

ABSTRACT

The current pandemic of COVID-19 has set off an urgent search for an effective vaccine. This search may well benefit from the experiences of the animal health profession in the development and use of coronavirus vaccines in domestic animal species. These animal vaccines will in no way protect humans against COVID-19 but knowledge of the difficulties encountered in vaccinating animals may help avoid or minimize similar problems arising in humans. Diverse coronaviruses can infect the domestic species from dogs and cats, to cattle and pigs to poultry. Many of these infections are controlled by routine vaccination. Thus, canine coronavirus vaccines are protective in puppies but the disease itself is mild and self-limiting. Feline coronavirus infections may be mild or may result in a lethal immune-mediated disease - feline infectious peritonitis. As a result, vaccination of domestic cats must seek to generate- protective immunity without causing immune-mediated disease. Vaccines against bovine coronavirus are widely employed in cattle where they protect against enteric and respiratory disease in young calves. Two major livestock species suffer from economically significant and severe coronavirus diseases. Thus, pigs may be infected with six different coronaviruses, one of which, porcine epidemic diarrhea, has proven difficult to control despite the development of several innovative vaccines. Porcine epidemic diarrhea virus undergoes frequent genetic changes. Likewise, infectious bronchitis coronavirus causes an economically devastating disease of chickens. It too undergoes frequent genetic shifts and as a result, can only be controlled by extensive and repeated vaccination. Other issues that have been encountered in developing these animal vaccines include a relatively short duration of protective immunity, and a lack of effectiveness of inactivated vaccines. On the other hand, they have been relatively cheap to make and lend themselves to mass vaccination procedures.


Subject(s)
Coronavirus Infections/veterinary , Livestock , Pets , Vaccination/veterinary , Viral Vaccines/therapeutic use , Animals , Cats , Cattle , Coronavirus Infections/prevention & control , Dogs , Poultry , Swine
17.
J Vet Emerg Crit Care (San Antonio) ; 30(4): 493-497, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-621233

ABSTRACT

BACKGROUND: The COVID-19 pandemic has presented veterinary emergency hospitals with unique challenges. Rapid online surveys represent an efficient way of collating responses to rapidly shifting circumstances. METHODS: Fifty, 24-h small animal emergency veterinary hospital representatives were recruited to participate in weekly surveys in April 2020 to catalog changes due to COVID-19 pandemic. KEY FINDINGS: The majority of emergency veterinary hospitals surveyed reported significant changes to day-to-day operations as a result of the COVID-19 pandemic. SIGNIFICANCE: Reporting of weekly survey results provides useful information on how emergency veterinary hospitals with similar challenges are responding to the COVID-19 pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Hospitals, Animal/trends , Pneumonia, Viral/epidemiology , Animals , Burnout, Professional/epidemiology , Burnout, Professional/etiology , Cats , Dogs , Emergencies/veterinary , Emergency Service, Hospital/trends , Female , Ferrets , Hospitals, Animal/economics , Male , Occupational Stress/epidemiology , Occupational Stress/etiology , Pandemics , Personal Protective Equipment/supply & distribution , Pharmaceutical Preparations/supply & distribution , Surveys and Questionnaires , United States/epidemiology
20.
J Pharmacokinet Pharmacodyn ; 47(3): 189-198, 2020 06.
Article in English | MEDLINE | ID: covidwho-324441

ABSTRACT

To face SARS-CoV-2 pandemic various attempts are made to identify potential effective treatments by repurposing available drugs. Among them, indomethacin, an anti-inflammatory drug, was shown to have potent in-vitro antiviral properties on human SARS-CoV-1, canine CCoV, and more recently on human SARS-CoV-2 at low micromolar range. Our objective was to show that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 and to provide criteria for comparing benefits of alternative dosage regimens using a model-based approach. A multi-stage model-based approach was developed to characterize % of recovery and viral load in CCoV-infected dogs, to estimate the PK of indomethacin in dog and human using published data after administration of immediate (IR) and sustained-release (SR) formulations, and to estimate the expected antiviral activity as a function of different assumptions on the effective exposure in human. Different dosage regimens were evaluated for IR formulation (25 mg and 50 mg three-times-a-day, and 25 mg four-times-a-day), and SR formulation (75 mg once and twice-a-day). The best performing dosing regimens were: 50 mg three-times-a-day for the IR formulation, and 75 mg twice-a-day for the SR formulation. The treatment with the SR formulation at the dose of 75 mg twice-a-day is expected to achieve a complete response in three days for the treatment in patients infected by the SARS-CoV-2 coronavirus. These results suggest that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 whose potential therapeutic effect need to be further assessed in a prospective clinical trial.


Subject(s)
Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Drug Dosage Calculations , Indomethacin/administration & dosage , Indomethacin/therapeutic use , Models, Biological , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/pharmacokinetics , Betacoronavirus/drug effects , Coronavirus Infections/virology , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/therapeutic use , Dogs , Humans , Indomethacin/pharmacokinetics , Pandemics , Pneumonia, Viral/virology , Viral Load/drug effects
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