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1.
BMJ Open Respir Res ; 9(1)2022 04.
Article in English | MEDLINE | ID: covidwho-1923267

ABSTRACT

There were respiratory consultant post vacancies in 82% of surveyed UK hospitals in 2021. Understanding respiratory trainees' career intentions is vital to plan and train a future respiratory workforce. In 2020, the British Thoracic Society surveyed trainee members (n=144) to assess career plans and perceived barriers and facilitators when applying for consultant posts. Most trainees (79, 55.6%) report intending to pursue UK-based posts with general internal medicine responsibilities. Consultant applications are influenced by location, hospital type, previous local experience and availability of subspecialty posts. Insufficient guidance is available regarding consultant applications.


Subject(s)
Career Choice , Pulmonary Medicine , Humans , Intention , Surveys and Questionnaires , United Kingdom
2.
Comput Biol Med ; 146: 105419, 2022 07.
Article in English | MEDLINE | ID: covidwho-1803804

ABSTRACT

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the vaccine effectiveness. Asymptomatic breakthrough infections have been a major problem in assessing vaccine effectiveness in populations globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines since whole virion vaccines generate antibodies against all the viral proteins. Here, we show how a statistical and machine learning (ML) based approach can be used to discriminate between SARS-CoV-2 infection and immune response to an inactivated whole virion vaccine (BBV152, Covaxin). For this, we assessed serial data on antibodies against Spike and Nucleocapsid antigens, along with age, sex, number of doses taken, and days since last dose, for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, our ensemble ML model classified 724 to be infected. For method validation, we determined the relative ability of a random subset of samples to neutralize Delta versus wild-type strain using a surrogate neutralization assay. We worked on the premise that antibodies generated by a whole virion vaccine would neutralize wild type more efficiently than delta strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, neutralization against Delta strain was more effective, indicating infection. We found 71.8% subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period. Our approach will help in real-world vaccine effectiveness assessments where whole virion vaccines are commonly used.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , Machine Learning , Pandemics , SARS-CoV-2 , Vaccines, Inactivated , Virion
3.
Nat Commun ; 13(1): 1726, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1773977

ABSTRACT

Immunization is expected to confer protection against infection and severe disease for vaccines while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies of an observational cohort of healthcare workers, we show that during a Severe Acute Respiratory Syndrome -Coronavirus 2 Delta-variant outbreak in Delhi, 25.3% (95% Confidence Interval 16.9-35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare workers were infected within less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, Inter Quartile Range 374) and without (342 U/ml, Inter Quartile Range 497), as was the induction of neutralization activity to wildtype. This was not vaccine failure since vaccine effectiveness estimate based on infection rates in an unvaccinated cohort were about 70% and most infections were asymptomatic. We find that while ChAdOx1-nCoV19 vaccination remains effective in preventing severe infections, it is unlikely to be completely able to block transmission and provide herd immunity.


Subject(s)
Asymptomatic Infections , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Health Personnel , Humans , Immunization , SARS-CoV-2 , Vaccination
4.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296195

ABSTRACT

Immunization is expected to confer protection against infection and severe disease for vaccinees, while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies, we show that during a severe SARS-CoV2 Delta-variant outbreak in Delhi, 25.3% (95% CI 16.9 - 35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare-workers (HCW) were infected within a period of less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, IQR 374) or not (342 U/ml, IQR 497), as was induction of neutralization activity to wildtype. Most infections were unrecognized. The Delta-variant thus causes frequent unrecognized breakthrough infections in adequately immunized subjects, reducing any herd-effect of immunity, and requiring reinstatement of preventive measures such as masking.

5.
Acta Med Acad ; 49(2): 130-143, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1414828

ABSTRACT

In this review, we discuss the latest developments in research pertaining to virus-induced asthma exacerbations and consider recent advances in treatment options. Asthma is a chronic disease of the airways that continues to impose a substantial clinical burden worldwide. Asthma exacerbations, characterised by an acute deterioration in respiratory symptoms and airflow obstruction, are associated with significant morbidity and mortality. These episodes are most commonly triggered by respiratory virus infections. The mechanisms underlying the pathogenesis of virus-induced exacerbations have been the focus of extensive biomedical research. Developing a robust understanding of the interplay between respiratory viruses and the host immune response will be critical for developing more efficacious, targeted therapies for exacerbations. CONCLUSION: There has been significant recent progress in our understanding of the mechanisms underlying virus-induced airway inflammation in asthma and these advances will underpin the development of future clinical therapies.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Antiviral Agents/therapeutic use , Asthma/drug therapy , Respiratory Tract Infections/drug therapy , Virus Diseases/drug therapy , Adenovirus Infections, Human/drug therapy , Adenovirus Infections, Human/immunology , Adenovirus Infections, Human/physiopathology , Administration, Inhalation , Asthma/immunology , Asthma/physiopathology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Disease Progression , Humans , Influenza, Human/drug therapy , Influenza, Human/immunology , Influenza, Human/physiopathology , Interferon-beta/therapeutic use , Macrolides/therapeutic use , Omalizumab/therapeutic use , Paramyxoviridae Infections/drug therapy , Paramyxoviridae Infections/immunology , Paramyxoviridae Infections/physiopathology , Picornaviridae Infections/drug therapy , Picornaviridae Infections/immunology , Picornaviridae Infections/physiopathology , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/physiopathology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/physiopathology , Virus Diseases/immunology , Virus Diseases/physiopathology
6.
Postgrad Med J ; 98(1159): 328-330, 2022 May.
Article in English | MEDLINE | ID: covidwho-1341342

ABSTRACT

The COVID-19 pandemic has had a significant impact on postgraduate medical training across all specialties. Although some traditional learning opportunities have been curtailed, there have been numerous examples of highly valuable educational experiences that have arisen during this time. Here, from a trainee perspective, we consider the educational merits of the re-emergence of 'firm-based' teams, new online learning opportunities, use of digital technologies and the rise of telephone clinics and new COVID-19 clinical services. As health services continue to recover from surges in COVID-19 cases, it is important to reflect on and recognise the value of these educational experiences so that helpful elements can be retained and embedded into training programmes for the benefit of both trainees and patients.


Subject(s)
COVID-19 , Education, Distance , COVID-19/epidemiology , Humans , Learning , Pandemics
7.
BMJ Open Respir Res ; 8(1)2021 04.
Article in English | MEDLINE | ID: covidwho-1172762

ABSTRACT

BACKGROUND: The symptoms, radiography, biochemistry and healthcare utilisation of patients with COVID-19 following discharge from hospital have not been well described. METHODS: Retrospective analysis of 401 adult patients attending a clinic following an index hospital admission or emergency department attendance with COVID-19. Regression models were used to assess the association between characteristics and persistent abnormal chest radiographs or breathlessness. RESULTS: 75.1% of patients were symptomatic at a median of 53 days post discharge and 72 days after symptom onset and chest radiographs were abnormal in 47.4%. Symptoms and radiographic abnormalities were similar in PCR-positive and PCR-negative patients. Severity of COVID-19 was significantly associated with persistent radiographic abnormalities and breathlessness. 18.5% of patients had unscheduled healthcare visits in the 30 days post discharge. CONCLUSIONS: Patients with COVID-19 experience persistent symptoms and abnormal blood biomarkers with a gradual resolution of radiological abnormalities over time. These findings can inform patients and clinicians about expected recovery times and plan services for follow-up of patients with COVID-19.


Subject(s)
Aftercare , Biomarkers/analysis , COVID-19 , Patient Discharge/standards , Radiography, Thoracic , Symptom Assessment , Aftercare/methods , Aftercare/organization & administration , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/epidemiology , COVID-19/physiopathology , Female , Humans , Male , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Radiography, Thoracic/methods , Radiography, Thoracic/statistics & numerical data , Recovery of Function , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , Time Factors , United Kingdom/epidemiology
8.
Eur Heart J ; 42(19): 1866-1878, 2021 05 14.
Article in English | MEDLINE | ID: covidwho-1087735

ABSTRACT

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.


Subject(s)
COVID-19 , Myocarditis , Contrast Media , Female , Gadolinium , Humans , Magnetic Resonance Imaging, Cine , Magnetic Resonance Spectroscopy , Male , Myocarditis/diagnostic imaging , Myocardium , Predictive Value of Tests , SARS-CoV-2 , Troponin , Ventricular Function, Left
9.
Future Healthc J ; 7(3): e88-e92, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-890684

ABSTRACT

Integration of primary and secondary care for the management of respiratory disease is a long-held ambition. Here, we describe how respiratory specialists at a large NHS trust, working with primary care clinicians in the area, set up a GP hotline and respiratory support service in response to the COVID-19 pandemic, with the aim of enhancing delivery of care to patients in this unprecedented time. Working across traditional organisational boundaries in this way confers benefits to patients and clinicians, illustrating the value of new, integrated models of care.

10.
Ann Am Thorac Soc ; 17(10): 1186-1194, 2020 10.
Article in English | MEDLINE | ID: covidwho-659009

ABSTRACT

The rapid global spread and significant mortality associated with the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection has spurred an urgent race to find effective treatments. Repurposing existing drugs is a particularly attractive approach as pharmacokinetic and safety data already exist; thus, development can leapfrog straight to clinical trials of efficacy, generating results far more quickly than de novo drug development. This review summarizes the state of play for the principle drugs identified as candidates to be repurposed for treating COVID-19 grouped by broad mechanism of action: antiviral, immune enhancing, and antiinflammatory or immunomodulatory. Patient selection, particularly with regard to disease stage, is likely to be key. To date, only dexamethasone and remdesivir have been shown to be effective, but several other promising candidates are in trials.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections , Immunologic Factors/pharmacology , Pandemics , Pneumonia, Viral , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Drug Discovery/methods , Drug Repositioning/methods , Humans , Patient Selection , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , SARS-CoV-2
11.
Am J Physiol Lung Cell Mol Physiol ; 318(6): L1244-L1247, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-260033

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a new rapidly spreading infectious disease. Current guidance from the World Health Organization (WHO) highlights asthmatics as a high-risk group for severe illness from COVID-19. Viruses are common triggers of asthma exacerbations and the current SARS-CoV-2 pandemic raises several questions regarding the optimum management strategies. Here, we discuss the contentious issue of whether the mainstay therapy systemic corticosteroids should be used in the routine management of COVID-19-associated asthma exacerbations. Recent guidance from the WHO has advised against the use of corticosteroids if COVID-19 is suspected due to concerns that these agents may impair protective innate antiviral immune responses. This may not be appropriate in the unique case of asthma exacerbation, a syndrome associated with augmented type 2 inflammation, a disease feature that is known to directly inhibit antiviral immunity. Corticosteroids, through their suppressive effects on type 2 inflammation, are thus likely to restore impaired antiviral immunity in asthma and, in contrast to non-asthmatic subjects, have beneficial clinical effects in the context of SARS-CoV-2 infection.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Asthma/drug therapy , Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , Antiviral Agents/therapeutic use , Asthma/virology , COVID-19 , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2
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