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PLoS Biol ; 19(12): e3001065, 2021 12.
Article in English | MEDLINE | ID: covidwho-1594053


The pandemic spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19), represents an ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 replication. Utilizing a three-dimensional (3D) air-liquid interface (ALI) model that closely mimics the natural tissue physiology of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. Respiratory tissue incubated at 40°C remained permissive to SARS-CoV-2 entry but refractory to viral transcription, leading to significantly reduced levels of viral RNA replication and apical shedding of infectious virus. We identify tissue temperature to play an important role in the differential regulation of epithelial host responses to SARS-CoV-2 infection that impact upon multiple pathways, including intracellular immune regulation, without disruption to general transcription or epithelium integrity. We present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication in respiratory epithelia. Our data identify an important role for tissue temperature in the epithelial restriction of SARS-CoV-2 independently of canonical interferon (IFN)-mediated antiviral immune defenses.

Epithelial Cells/immunology , Hot Temperature , Immunity, Innate/immunology , Interferons/immunology , Respiratory Mucosa/immunology , SARS-CoV-2/immunology , Virus Replication/immunology , Adolescent , Animals , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Chlorocebus aethiops , Epithelial Cells/metabolism , Epithelial Cells/virology , Female , Gene Expression Profiling/methods , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/genetics , Interferons/genetics , Interferons/metabolism , Male , Middle Aged , Models, Biological , RNA-Seq/methods , Respiratory Mucosa/metabolism , Respiratory Mucosa/virology , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Tissue Culture Techniques , Vero Cells , Virus Replication/genetics , Virus Replication/physiology
Cureus ; 13(3): e14114, 2021 Mar 25.
Article in English | MEDLINE | ID: covidwho-1204353


Background The coronavirus disease 2019 (COVID-19) pandemic has led to a focus on non-face-to-face (NF2F) orthopedic clinics. In this study, our aim was to establish whether NF2F clinics are sustainable according to the "triple bottom line" framework by taking into account the impact on patients, the planet, and the financial cost. Methodology This retrospective cohort study was carried out at a large district general hospital with 261 patients identified as having undergone face-to-face (F2F) or NF2F orthopedic consultations (April 2020). These patients were contacted by telephone to establish their experience, mode of transport, and preference for future consultations. Data were also collected relating to environmental and financial costs to the patient and the trust. Results The final analysis included 180 (69%) patients: 42% had an F2F consultation and 58% NF2F consultation. There was no significant difference between each group in terms of convenience, ease of communication, subjective patient safety, or overall satisfaction rating (p > 0.05). Overall, 80% of NF2F patients would be happy with virtual consultations in the future. The mean journey distance was 18.6 miles leading to a reduction in total carbon emissions of 563.9 kgCO2e (66%), equating to 2,106 miles in a medium-sized car. The hospital visit carbon cost (heating, lighting, and waste generation) was reduced by 3,967 kgCO2e (58%). The financial cost (petrol and parking) was also reduced by an average of £8.96 per person. Conclusions NF2F consultations are aligned to the National Health Service's "Long Term Plan": (i) delivering high patient satisfaction with equivalent outcomes as F2F consultations; (ii) reducing carbon emissions from transportation and hospital running; and (iii) becoming cheaper.

Vet Rec ; 188(8): e247, 2021 04.
Article in English | MEDLINE | ID: covidwho-1198417


OBJECTIVES: The aim of the study was to find evidence of SARS-CoV-2 infection in UK cats. DESIGN: Tissue samples were tested for SARS-CoV-2 antigen using immunofluorescence and for viral RNA by in situ hybridisation. A set of 387 oropharyngeal swabs that had been submitted for routine respiratory pathogen testing was tested for SARS-CoV-2 RNA using reverse transcriptase quantitative PCR. RESULTS: Lung tissue collected post-mortem from cat 1 tested positive for both SARS-CoV-2 nucleocapsid antigen and RNA. SARS-CoV-2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the viral genome revealed five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS-CoV-2 sequence, and this human virus contained eight SNPs compared to the original Wuhan-Hu-1 reference sequence. An analysis of the viral genome of cat 2 together with nine other feline-derived SARS-CoV-2 sequences from around the world revealed no shared cat-specific mutations. CONCLUSIONS: These findings indicate that human-to-cat transmission of SARS-CoV-2 occurred during the COVID-19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the ability of the new coronavirus to infect different species, it will be important to monitor for human-to-cat, cat-to-cat and cat-to-human transmission.

COVID-19/veterinary , Cat Diseases/virology , Lung/virology , SARS-CoV-2/isolation & purification , Zoonoses , Animals , COVID-19/epidemiology , COVID-19/transmission , Cats , Female , Humans , RNA, Viral , SARS-CoV-2/genetics , United Kingdom/epidemiology