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1.
Adv Exp Med Biol ; 1318: 449-468, 2021.
Artículo en Inglés | MEDLINE | ID: covidwho-1222729

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel zoonotic virus identified as the cause of coronavirus disease 2019 (COVID-19) that has crossed species and infected humans. In order to develop new insights on the immune-based treatments against this disease, it is vital to understand the immunopathology of the COVID-19, implications of the immune response to SARS-CoV-2, and immune dysfunction in response to SARS-CoV-2. There is no approved drug for the treatment of COVID-19. It is, thus, promising to design immune-based treatments that inhibit the infectious mechanism of the virus, improve the inadequate immune response, or regulate the hyperactivated immune response in severely ill patients. According to the antiviral immune response against the virus, antibody-based immunotherapies of COVID-19 include injection of convalescent plasma from recovered patients, high-dose intravenous immunoglobulins (IVIG), monoclonal antibodies, and polyclonal antibodies. Also, cell-based treatment, vaccine-based approaches, cytokine-based immunotherapy, immune checkpoint inhibitors, JAK inhibitors, decoy receptors, and immunosuppressive drugs are discussed in this chapter.


Asunto(s)
Infecciones por Coronavirus , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Humanos , Inmunización Pasiva
3.
PLoS One ; 15(11): e0241959, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-1218365

RESUMEN

The coronavirus disease 2019 (Covid-19) pandemic, caused by SARS-CoV-2, has resulted in a global testing supply shortage. In response, pooled testing has emerged as a promising strategy that can immediately increase testing capacity. In pooled sample testing, multiple samples are combined (or pooled) together and tested as a single unit. If the pool is positive, the individual samples can then be individually tested to identify the positive case(s). Here, we provide support for the adoption of sample pooling with the point-of-care Cepheid Xpert® Xpress SARS-CoV-2 molecular assay. Corroborating previous findings, the limit of detection of this assay was comparable to laboratory-developed reverse-transcription quantitative PCR SARS-CoV-2 tests, with observed detection below 100 copies/mL. The Xpert® Xpress assay detected SARS-CoV-2 after samples with minimum viral loads of 461 copies/mL were pooled in groups of six. Based on these data, we recommend the adoption of pooled testing with the Xpert® Xpress SARS-CoV-2 assay where warranted based on public health needs. The suggested number of samples per pool, or the pooling depth, is unique for each point-of-care testing site and can be determined by the positive test rates. To statistically determine appropriate pooling depth, we have calculated the pooling efficiency for numerous combinations of pool sizes and test rates. This information is included as a supplemental dataset that we encourage public health authorities to use as a guide to make recommendations that will maximize testing capacity and resource conservation.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , ARN Viral/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/virología , Pruebas en el Punto de Atención , ARN Viral/genética , Juego de Reactivos para Diagnóstico , Manejo de Especímenes , Carga Viral
4.
Appl Environ Microbiol ; 86(18)2020 09 01.
Artículo en Inglés | MEDLINE | ID: covidwho-1218186

RESUMEN

Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data regarding coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D values (i.e., the time to obtain a log10 reduction of virus infectivity), including values for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global data set of D values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points, or any coronavirus strains belonging to Alphacoronavirus and Betacoronavirus genera.IMPORTANCE The prediction of the persistence of SARS-CoV-2 on fomites is essential in investigating the importance of contact transmission. This study collects available information on inactivation kinetics of coronaviruses in both solid and liquid fomites and creates a mathematical model for the impact of temperature and relative humidity on virus persistence. The predictions of the model can support more robust decision-making and could be useful in various public health contexts. A calculator for the natural clearance of SARS-CoV-2 depending on temperature and relative humidity could be a valuable operational tool for public authorities.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/virología , Modelos Biológicos , Neumonía Viral/virología , Inactivación de Virus , Fómites/virología , Humanos , Humedad , Pandemias , Salud Pública , Suspensiones , Temperatura
6.
Int J Clin Pract ; 74(8): e13512, 2020 08.
Artículo en Inglés | MEDLINE | ID: covidwho-1218110
9.
Clin Exp Dermatol ; 45(6): 748-749, 2020 08.
Artículo en Inglés | MEDLINE | ID: covidwho-1218094
12.
Clin Infect Dis ; 71(15): 863-865, 2020 07 28.
Artículo en Inglés | MEDLINE | ID: covidwho-1217826

RESUMEN

We analyzed age-/sex-specific morbidity and mortality data from the SARS-CoV-2 pandemic in China and Republic of Korea (ROK). Data from China exhibit a Gaussian distribution with peak morbidity in the 50-59-year cohort, while the ROK data have a bimodal distribution with the highest morbidity in the 20-29-year cohort.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/mortalidad , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Adulto , Betacoronavirus/patogenicidad , China/epidemiología , Infecciones por Coronavirus/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Pandemias , Neumonía Viral/virología , República de Corea/epidemiología , Adulto Joven
13.
Clin Infect Dis ; 71(15): 786-792, 2020 07 28.
Artículo en Inglés | MEDLINE | ID: covidwho-1217824

RESUMEN

BACKGROUND: Rapid identification of COVID-19 cases, which is crucial to outbreak containment efforts, is challenging due to the lack of pathognomonic symptoms and in settings with limited capacity for specialized nucleic acid-based reverse transcription polymerase chain reaction (PCR) testing. METHODS: This retrospective case-control study involves subjects (7-98 years) presenting at the designated national outbreak screening center and tertiary care hospital in Singapore for SARS-CoV-2 testing from 26 January to 16 February 2020. COVID-19 status was confirmed by PCR testing of sputum, nasopharyngeal swabs, or throat swabs. Demographic, clinical, laboratory, and exposure-risk variables ascertainable at presentation were analyzed to develop an algorithm for estimating the risk of COVID-19. Model development used Akaike's information criterion in a stepwise fashion to build logistic regression models, which were then translated into prediction scores. Performance was measured using receiver operating characteristic curves, adjusting for overconfidence using leave-one-out cross-validation. RESULTS: The study population included 788 subjects, of whom 54 (6.9%) were SARS-CoV-2 positive and 734 (93.1%) were SARS-CoV-2 negative. The median age was 34 years, and 407 (51.7%) were female. Using leave-one-out cross-validation, all the models incorporating clinical tests (models 1, 2, and 3) performed well with areas under the receiver operating characteristic curve (AUCs) of 0.91, 0.88, and 0.88, respectively. In comparison, model 4 had an AUC of 0.65. CONCLUSIONS: Rapidly ascertainable clinical and laboratory data could identify individuals at high risk of COVID-19 and enable prioritization of PCR testing and containment efforts. Basic laboratory test results were crucial to prediction models.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/virología , Pruebas Diagnósticas de Rutina/métodos , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Pandemias , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa/métodos , Estudios Retrospectivos , Singapur/epidemiología , Esputo/virología , Adulto Joven
14.
Clin Infect Dis ; 71(15): 778-785, 2020 07 28.
Artículo en Inglés | MEDLINE | ID: covidwho-1217823

RESUMEN

BACKGROUND: The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. METHODS: The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. RESULTS: The median duration of IgM and IgA antibody detection was 5 (IQR, 3-6) days, while IgG was detected 14 (IQR, 10-18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). CONCLUSIONS: The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.


Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/inmunología , Inmunidad Humoral/inmunología , Neumonía Viral/diagnóstico , Neumonía Viral/inmunología , Adulto , Secuencia de Aminoácidos , Anticuerpos Antivirales/inmunología , Niño , Preescolar , Infecciones por Coronavirus/virología , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa/métodos
15.
Clin Infect Dis ; 71(15): 769-777, 2020 07 28.
Artículo en Inglés | MEDLINE | ID: covidwho-1217822

RESUMEN

BACKGROUND: From December 2019 to February 2020, 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. Related clinical features are needed. METHODS: We reviewed 69 patients who were hospitalized in Union hospital in Wuhan between 16 January and 29 January 2020. All patients were confirmed to be infected with SARS-CoV-2, and the final date of follow-up was 4 February 2020. RESULTS: The median age of 69 enrolled patients was 42.0 years (interquartile range 35.0-62.0), and 32 patients (46%) were men. The most common symptoms were fever (60 [87%]), cough (38 [55%]), and fatigue (29 [42%]). Most patients received antiviral therapy (66 [98.5%] of 67 patients) and antibiotic therapy (66 [98.5%] of 67 patients). As of 4 February 2020, 18 (26.9%) of 67 patients had been discharged, and 5 patients had died, with a mortality rate of 7.5%. According to the lowest SpO2 during admission, cases were divided into the SpO2 ≥ 90% group (n = 55) and the SpO2 < 90% group (n = 14). All 5 deaths occurred in the SpO2 < 90% group. Compared with SpO2 ≥ 90% group, patients of the SpO2 < 90% group were older and showed more comorbidities and higher plasma levels of interleukin (IL) 6, IL10, lactate dehydrogenase, and C reactive protein. Arbidol treatment showed tendency to improve the discharging rate and decrease the mortality rate. CONCLUSIONS: COVID-19 appears to show frequent fever, dry cough, and increase of inflammatory cytokines, and induced a mortality rate of 7.5%. Older patients or those with underlying comorbidities are at higher risk of death.


Asunto(s)
Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Neumonía Viral/patología , Neumonía Viral/virología , Adulto , Anciano , Betacoronavirus/patogenicidad , Proteína C-Reactiva/metabolismo , China , Infecciones por Coronavirus/metabolismo , Tos/metabolismo , Tos/patología , Tos/virología , Femenino , Fiebre/metabolismo , Fiebre/patología , Fiebre/virología , Hospitalización , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Pandemias , Alta del Paciente , Neumonía Viral/metabolismo
16.
Lancet ; 395(10238): 1705-1714, 2020 05 30.
Artículo en Inglés | MEDLINE | ID: covidwho-1217628

RESUMEN

BACKGROUND: Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19. METHODS: In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437. FINDINGS: We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39·0%) were female and the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62-2·41) and risk factors (1·46, 1·23-1·73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77-1·15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64-1·00) or angiotensin-receptor blockers (1·10, 0·88-1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI 0·34-0·80). The adjusted ORs were similar across severity degrees of COVID-19. INTERPRETATION: RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19. FUNDING: Instituto de Salud Carlos III.


Asunto(s)
Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Infecciones por Coronavirus/epidemiología , Hospitalización/estadística & datos numéricos , Neumonía Viral/epidemiología , Sistema Renina-Angiotensina , Anciano , Anciano de 80 o más Años , Comorbilidad , Infecciones por Coronavirus/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Pandemias , Neumonía Viral/complicaciones , Renina/antagonistas & inhibidores , Factores de Riesgo , España/epidemiología
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