RESUMEN
Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non-hospitalized SARS-CoV-2-infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT-PCR confirmed, non-hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti-spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS-CoV-2 infection.
Asunto(s)
Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Antígenos Virales/inmunología , COVID-19/sangre , COVID-19/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Humanos , SalivaRESUMEN
Dried blood spot (DBS) samples can be used for the detection of severe acute respiratory syndrome coronavirus 2 spike antibodies. DBS sampling is comparable to matched serum samples with a relative 98.1% sensitivity and 100% specificity. Thus, DBS sampling offers an alternative for population-wide serologic testing in the coronavirus pandemic.
Asunto(s)
COVID-19/diagnóstico , Pruebas con Sangre Seca/métodos , Anticuerpos Antivirales/inmunología , Prueba Serológica para COVID-19/métodos , Estudios de Casos y Controles , Pruebas con Sangre Seca/economía , Humanos , Valor Predictivo de las Pruebas , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/aislamiento & purificaciónRESUMEN
OBJECTIVE: To determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers. DESIGN: A cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020. SETTING: University Hospitals Birmingham NHS Foundation Trust (UHBFT), UK. PARTICIPANTS: 545 asymptomatic healthcare workers were recruited while at work. Participants were invited to participate via the UHBFT social media. Exclusion criteria included current symptoms consistent with COVID-19. No potential participants were excluded. INTERVENTION: Participants volunteered a nasopharyngeal swab and a venous blood sample that were tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 spike glycoprotein antibodies, respectively. Results were interpreted in the context of prior illnesses and the hospital departments in which participants worked. MAIN OUTCOME MEASURE: Proportion of participants demonstrating infection and positive SARS-CoV-2 serology. RESULTS: The point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545). The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516). Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%, χ2=21.1034, p<0.0001) and quantitatively greater antibody responses than those who had remained asymptomatic. Seroprevalence was greatest among those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%), with lower rates observed in participants working in intensive care (14.8%). BAME (Black, Asian and minority ethnic) ethnicity was associated with a significantly increased risk of seropositivity (OR: 1.92, 95% CI 1.14 to 3.23, p=0.01). Working on the intensive care unit was associated with a significantly lower risk of seropositivity compared with working in other areas of the hospital (OR: 0.28, 95% CI 0.09 to 0.78, p=0.02). CONCLUSIONS AND RELEVANCE: We identify differences in the occupational risk of exposure to SARS-CoV-2 between hospital departments and confirm asymptomatic seroconversion occurs in healthcare workers. Further investigation of these observations is required to inform future infection control and occupational health practices.
Asunto(s)
Anticuerpos Antivirales/sangre , Enfermedades Asintomáticas , COVID-19/diagnóstico , Personal de Salud/estadística & datos numéricos , Pandemias , SARS-CoV-2/inmunología , Adulto , COVID-19/epidemiología , COVID-19/virología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/análisis , SARS-CoV-2/genética , Estudios SeroepidemiológicosRESUMEN
OBJECTIVES: The study aims to investigate the short-term associations between exposure to ambient air pollution (nitrogen dioxide (NO2), particulate matter pollution-particles with diameter<2.5 µm (PM2.5) and PM10) and incidence of asthma hospital admissions among adults, in Oxford, UK. DESIGN: Retrospective time-series study. SETTING: Oxford City (postcode areas OX1-OX4), UK. PARTICIPANTS: Adult population living within the postcode areas OX1-OX4 in Oxford, UK from 1 January 2015 to 31 December 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: Hourly NO2, PM2.5 and PM10 concentrations and meteorological data for the period 1 January 2015 to 31 December 2020 were analysed and used as exposures. We used Poisson linear regression analysis to identify independent associations between air pollutant concentrations and asthma admissions rate among the adult study population, using both single (NO2, PM2.5, PM10) and multipollutant (NO2 and PM2.5, NO2 and PM10) models, where they adjustment for temperature and relative humidity. RESULTS: The overall 5-year average asthma admissions rate was 78 per 100 000 population during the study period. The annual average rate decreased to 46 per 100 000 population during 2020 (incidence rate ratio 0.58, 95% CI 0.42 to 0.81, p<0.001) compared to the prepandemic years (2015-2019). In single-pollutant analysis, we observed a significantly increased risk of asthma admission associated with each 1 µg/m3 increase in monthly concentrations of NO2 4% (95% CI 1.009% to 1.072%), PM2.5 3% (95% CI 1.006% to 1.052%) and PM10 1.8% (95% CI 0.999% to 1.038%). However, in the multipollutant regression model, the effect of each individual pollutant was attenuated. CONCLUSIONS: Ambient NO2 and PM2.5 air pollution exposure increased the risk of asthma admissions in this urban setting. Improvements in air quality during COVID-19 lockdown periods may have contributed to a substantially reduced acute asthma disease burden. Large-scale measures to improve air quality have potential to protect vulnerable people living with chronic asthma in urban areas.
Asunto(s)
Contaminación del Aire , Asma , COVID-19 , Contaminantes Ambientales , Adulto , Humanos , Dióxido de Nitrógeno , Pandemias , Estudios Retrospectivos , Control de Enfermedades Transmisibles , Material Particulado , Hospitales , Reino UnidoRESUMEN
BACKGROUND: In January 2020 reports of unidentified severe respiratory illness were described in Wuhan, China. A rapid expansion in cases affecting most countries around the globe led to major changes in the way people live their daily lives. In the United Kingdom, the Department of Health and Social Care directed healthcare providers to establish additional resources to manage the anticipated surge in cases that could overwhelm the health services. A priority area was testing for SARS-CoV-2 RNA and its detection by qualitative RT-PCR. DESIGN: A laboratory workflow twinning research environment with clinical laboratory capabilities was implemented and validated in the University of Birmingham within 4 days of the project initiation. The diagnostic capability was centred on an IVD CE-marked RT-PCR kit and designed to provide surge capacity to the nearby Queen Elizabeth Hospital. The service was initially tasked with testing healthcare workers (HCW) using throat swabs, and subsequently the process investigated the utility of using saliva as an alternative sample type. RESULTS: Between the 8th April 2020 and the 30th April 2020, the laboratory tested a total of 1282 HCW for SARS-CoV-2 RNA in throat swabs. RNA was detected in 54 % of those who reported symptoms compatible with COVID-19, but in only 4% who were asymptomatic. CONCLUSION: This capability was established rapidly and utilised a cold-chain free methodology, applicable to a wide range of settings, and which can provide surge capacity and support to clinical laboratories facing increasing pressure during periods of national crisis.
Asunto(s)
Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , ARN Viral/sangre , Betacoronavirus/genética , COVID-19 , Prueba de COVID-19 , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/virología , SARS-CoV-2 , Saliva/virología , Capacidad de Reacción , Reino Unido , Flujo de TrabajoRESUMEN
BACKGROUND: Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. METHODS: We systemically developed an ELISA assay, optimising different antigens and amplification steps, in serum and saliva from symptomatic and asymptomatic SARS-CoV-2-infected subjects. RESULTS: Using trimeric spike glycoprotein, rather than nucleocapsid enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike, but not nucleocapsid, IgG, IgA and IgM antibody responses were readily detectable in saliva from non-hospitalized symptomatic and asymptomatic individuals. Antibody responses in saliva and serum were largely independent of each other and symptom reporting. CONCLUSIONS: Detecting antibody responses in both saliva and serum is optimal for determining virus exposure and understanding immune responses after SARS-CoV-2 infection. FUNDING: This work was funded by the University of Birmingham, the National Institute for Health Research (UK), the NIH National Institute for Allergy and Infectious Diseases, the Bill and Melinda Gates Foundation and the University of Southampton.
RESUMEN
BACKGROUND: All health care professionals in the UK are expected to have the medical leadership and management (MLM) skills necessary for improving patient care, as stipulated by the UK General Medical Council (GMC). CONTEXT: Newly graduated doctors reported insufficient knowledge about leadership and quality improvement skills, despite all UK medical schools reporting that MLM is taught within their curriculum. INNOVATION: A medical student society organised a series of extracurricular educational events focusing on leadership topics. The society recognised that the events needed to be useful and interesting to attract audiences. Therefore, clinical leaders in exciting fields were invited to talk about their experiences and case studies of personal leadership challenges. The emphasis on personal stories, from respected leaders, was a deliberate strategy to attract students and enhance learning. Evaluation data were collected from the audiences to improve the quality of the events and to support a business case for an intercalated degree in MLM. IMPLICATIONS: When leadership and management concepts are taught through personal stories, students find it interesting and are prepared to give up their leisure time to engage with the subject. Students appear to recognise the importance of MLM knowledge to their future careers, and are able to organise their own, and their peers', learning and development. Organising these events and collecting feedback can provide students with opportunities to practise leadership, management and quality improvement skills. These extracurricular events, delivered through a student society, allow for subjects to be discussed in more depth and can complement an already crowded undergraduate curriculum. Newly graduated doctors reported insufficient knowledge about leadership and quality improvement skills.