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1.
Ann Lab Med ; 41(2): 129-138, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33063674

RESUMEN

Since its first report in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly emerged as a pandemic affecting nearly all countries worldwide. As the COVID-19 pandemic progresses, the need to identify genetic risk factors for susceptibility to this serious illness has emerged. Host genetic factors, along with other risk factors may help determine susceptibility to respiratory tract infections. It is hypothesized that the ACE2 gene, encoding angiotensin-converting enzyme 2 (ACE2), is a genetic risk factor for SARS-CoV-2 infection and is required by the virus to enter cells. Together with ACE2, transmembrane protease serine 2 (TMPRSS2) and dipeptidyl peptidase-4 (DPP4) also play an important role in disease severity. Evaluating the role of genetic variants in determining the direction of respiratory infections will help identify potential drug target candidates for further study in COVID-19 patients. We have summarized the latest reports demonstrating that ACE2 variants, their expression, and epigenetic factors may influence an individual's susceptibility to SARS-CoV-2 infection and disease outcome.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/patología , Variación Genética , Neumonía Viral/patología , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Susceptibilidad a Enfermedades , Expresión Génica , Humanos , Pandemias , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/virología , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Índice de Severidad de la Enfermedad
2.
J Infect Chemother ; 27(1): 70-75, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32950393

RESUMEN

OBJECTIVES: The symptoms of Coronavirus disease 2019 (COVID-19) vary among patients. The aim of this study was to investigate the clinical manifestation and disease duration in young versus elderly patients. METHODS: We retrospectively analyzed 187 patients (87 elderly and 100 young patients) with confirmed COVID-19. The clinical characteristics and chest computed tomography (CT) extent as defined by a score were compared between the two groups. RESULTS: The numbers of asymptomatic cases and severe cases were significantly higher in the elderly group (elderly group vs. young group; asymptomatic cases, 31 [35.6%] vs. 10 [10%], p < 0.0001; severe cases, 25 [28.7%] vs. 8 [8.0%], p = 0.0002). The proportion of asymptomatic patients and severe patients increased across the 10-year age groups. There was no significant difference in the total CT score and number of abnormal cases. A significant positive correlation between the disease duration and patient age was observed in asymptomatic patients (ρ = 0.4570, 95% CI 0.1198-0.6491, p = 0.0034). CONCLUSIONS: Although the extent of lung involvement did not have a significant difference between the young and elderly patients, elderly patients were more likely to have severe clinical manifestations. Elderly patients were also more likely to be asymptomatic and a source of COVID-19 viral shedding.


Asunto(s)
Infecciones Asintomáticas/epidemiología , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Esparcimiento de Virus , Adulto , Factores de Edad , Anciano , Betacoronavirus , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/patología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X
3.
Am J Hum Genet ; 108(1): 194-201, 2021 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-33357513

RESUMEN

Given the coronavirus disease 2019 (COVID-19) pandemic, investigations into host susceptibility to infectious diseases and downstream sequelae have never been more relevant. Pneumonia is a lung disease that can cause respiratory failure and hypoxia and is a common complication of infectious diseases, including COVID-19. Few genome-wide association studies (GWASs) of host susceptibility and severity of pneumonia have been conducted. We performed GWASs of pneumonia susceptibility and severity in the Vanderbilt University biobank (BioVU) with linked electronic health records (EHRs), including Illumina Expanded Multi-Ethnic Global Array (MEGAEX)-genotyped European ancestry (EA, n= 69,819) and African ancestry (AA, n = 15,603) individuals. Two regions of large effect were identified: the CFTR locus in EA (rs113827944; OR = 1.84, p value = 1.2 × 10-36) and HBB in AA (rs334 [p.Glu7Val]; OR = 1.63, p value = 3.5 × 10-13). Mutations in these genes cause cystic fibrosis (CF) and sickle cell disease (SCD), respectively. After removing individuals diagnosed with CF and SCD, we assessed heterozygosity effects at our lead variants. Further GWASs after removing individuals with CF uncovered an additional association in R3HCC1L (rs10786398; OR = 1.22, p value = 3.5 × 10-8), which was replicated in two independent datasets: UK Biobank (n = 459,741) and 7,985 non-overlapping BioVU subjects, who are genotyped on arrays other than MEGAEX. This variant was also validated in GWASs of COVID-19 hospitalization and lung function. Our results highlight the importance of the host genome in infectious disease susceptibility and severity and offer crucial insight into genetic effects that could potentially influence severity of COVID-19 sequelae.


Asunto(s)
/complicaciones , Interacciones Huésped-Patógeno/genética , Neumonía Viral/complicaciones , Neumonía Viral/genética , Bronquitis/genética , /fisiopatología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Bases de Datos Genéticas , Registros Electrónicos de Salud , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Hemoglobinas/genética , Humanos , Pacientes Internos , Desequilibrio de Ligamiento , Masculino , Pacientes Ambulatorios , Neumonía Viral/patología , Neumonía Viral/fisiopatología , Polimorfismo de Nucleótido Simple/genética , Análisis de Componente Principal , Enfermedad Pulmonar Obstructiva Crónica/genética , Reproducibilidad de los Resultados , Reino Unido
5.
PLoS One ; 15(12): e0243598, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33315903

RESUMEN

BACKGROUND: The search for a SARS-CoV-2 treatment has emerged as a worldwide priority. We evaluated the role of chloroquine and its derivatives in COVID-19 in Spanish individuals. METHODS: We performed a survey addressed to patients regularly taking chloroquine and its derivatives for the control of their autoimmune diseases. The survey was distributed with special attention to Spanish patient associations centred on autoimmune diseases and rheumatology and to the general population. A sample of untreated subjects was matched to the treated group according to sex, age range and incidence region. COVID-19 disease prevalence was compared between treated and untreated-matched control sample. RESULTS: A total of 319 surveys of patients regularly taking chloroquine and its derivatives were recovered for further analysis. The prevalence of declared COVID-19 status in the treated group was 5.3% and the mean prevalence among the untreated-matched groups was 3.4%. A community exposition to COVID-19 was associated with a greater prevalence of COVID-19 in both, treated (17.0% vs. 3.2%; p-value<0.001) and untreated groups (13.4% vs. 1.1%; p-value = 0.027). CONCLUSION: We did not find differences of reported COVID-19 cases between treated and untreated groups, indicating a lack of protection by regular administration of chloroquine and its derivative drugs on COVID-19 infection. Of relevance, data indicates that patients that regularly take chloroquine derivatives are exposed to SARS-CoV-2 infection and must take the same protection measures as the general population.


Asunto(s)
/tratamiento farmacológico , Cloroquina/uso terapéutico , Pandemias , /patogenicidad , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , Antivirales/uso terapéutico , /patología , Cloroquina/efectos adversos , Cloroquina/análogos & derivados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/patología , Neumonía Viral/terapia , Neumonía Viral/virología , Adulto Joven
6.
BMC Infect Dis ; 20(1): 961, 2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33334317

RESUMEN

BACKGROUND: The clinical characteristics of patients with confirmed 2019 novel coronavirus disease (COVID-19) in Jilin Province, China were investigated. METHODS: Clinical, laboratory, radiology, and treatment data of 41 hospitalized patients with confirmed COVID-19 were retrospectively collected. The population was stratified by disease severity as mild, moderate, or severe, based on guidelines of the National Health and Medical Commission of China. RESULTS: The 41 hospitalized patients with COVID-19 were studied, and the median age was 45 years (interquartile range [IQR], 31-53; range, 10-87 years) and 18 patients (43.9%) were female. All of the patients had recently visited Wuhan or other places (ie, Beijing, Thailand) or had Wuhan-related exposure. Common symptoms included fever (32[78%]) and cough (29[70.7%]). All patients were without hepatitis B/C virus hepatitis. CRP (C-reactive protein, 11.3 mg/L [interquartile range {IQR}, 2.45-35.2]) was elevated in 22 patients (53.7%), and cardiac troponin I (1.5 ng/mL [IQR, 0.8-5.0]) was elevated in 41 patients (100%). Chest computed tomographic scans showed bilateral ground glass opacity (GGO) or GGO with consolidation in the lungs of 27(65.9%) patients. 31(75.6%) patients had an abnormal electrocardiograph (ECG). Comparing the three groups, the levels of CRP and cardiac troponin I, GGO distribution in bilateral lungs, and electrocardiogram changes were statistically significant (p < 0.05). Cardiac troponin I had a strong positive correlation with CRP (r = 0.704, p = 0.042) and LDH (r = 0.738, p = 0.037). CONCLUSION: Significant differences among the groups suggest that several clinical parameters may serve as biomarkers of COVID-19 severity at hospital admission. Elevated cTnI could be considered as a predictor of severe COVID-19, reflecting the prognosis of patients with severe COVID-19. The results warrant further inspection and confirmation.


Asunto(s)
/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , /patología , Niño , China/epidemiología , Femenino , Corazón/fisiopatología , Hospitalización , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Persona de Mediana Edad , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/patología , Neumonía Viral/fisiopatología , Pronóstico , Estudios Retrospectivos , Adulto Joven
7.
Rev. Hosp. Ital. B. Aires (2004) ; 40(4): 227-232, dic. 2020. ilus, tab
Artículo en Español | LILACS | ID: biblio-1145596

RESUMEN

La enfermedad producida por el nuevo coronavirus SARS-CoV-2 se identificó por primera vez en diciembre de 2019 en la ciudad de Wuhan, en la República Popular China, y en pocos meses se convirtió en una pandemia. Desde el comienzo ha sido un desafío mundial, que amenazó la salud pública y obligó a tomar medidas estrictas de aislamiento social. Como consecuencia de la emergencia sanitaria se ha producido una reducción importante de la actividad asistencial, que puso en riesgo el acceso y la continuidad de los métodos anticonceptivos, exponiendo a mujeres a embarazos no intencionales. Los derechos sexuales y reproductivos resultan esenciales y deben garantizarse siempre. (AU)


The disease caused by the new coronavirus SARS-CoV-2 was identified for the first time in December 2019 in the city of Wuhan, in the People's Republic of China, and within a few months it became a pandemic. From the beginning, it has been a global challenge, threatening public health, having to take strict measures of social isolation. As a consequence of the health emergency, there has been a significant reduction in healthcare activity, putting access and continuity of contraceptive methods at risk, exposing women to unintended pregnancies. Sexual and reproductive rights are essential and must always be guaranteed. (AU)


Asunto(s)
Humanos , Femenino , Neumonía Viral/complicaciones , Infecciones por Coronavirus/complicaciones , Anticoncepción Hormonal/métodos , Neumonía Viral/patología , Embarazo no Deseado , Infecciones por Coronavirus/patología , Anticonceptivos/administración & dosificación , Anticonceptivos/clasificación , Anticonceptivos/provisión & distribución , Derechos Sexuales y Reproductivos , Coagulación Intravascular Diseminada/etiología , Tromboembolia Venosa/etiología , Pandemias , Betacoronavirus , Accesibilidad a los Servicios de Salud
8.
In Vivo ; 34(6): 3723-3730, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33144490

RESUMEN

BACKGROUND/AIM: Influenza viruses, corona viruses and related pneumotropic viruses cause sickness and death partly by inducing cytokine storm, a hyper-proinflammatory host response by immune cells and cytokines in the host airway. Based on our in vivo experience with digitoxin as an inhibitor of TNFα-driven NFĸB signaling for cytokine expression in prostate cancer in rats and in cystic fibrosis in humans, we hypothesize that this drug will also block a virally-activated cytokine storm. Materials Methods: Digitoxin was administered intraperitoneally to cotton rats, followed by intranasal infection with 107TCID50/100 g of cotton rat with influenza strain A/Wuhan/H3N2/359/95. Daily digitoxin treatment continued until harvest on day 4 of the experiment. RESULTS: The cardiac glycoside digitoxin significantly and differentially suppressed levels of the cytokines TNFα, GRO/KC, MIP2, MCP1, and IFNγ, in the cotton rat lung in the presence of influenza virus. CONCLUSION: Since cytokine storm is a host response, we suggest that digitoxin may have a therapeutic potential not only for influenza and but also for coronavirus infections.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Digitoxina/farmacología , Pulmón/virología , Neumonía Viral/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Citocinas/biosíntesis , Citocinas/genética , Modelos Animales de Enfermedad , Humanos , Gripe Humana/tratamiento farmacológico , Gripe Humana/metabolismo , Gripe Humana/virología , Pulmón/patología , Masculino , FN-kappa B/genética , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/patología , Neumonía Viral/virología , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/virología , Ratas , Factor de Necrosis Tumoral alfa/genética
9.
In Vivo ; 34(6): 3747-3751, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33144493

RESUMEN

BACKGROUND/AIM: Tracheostomy performed on patients with Coronavirus disease 2019 (COVID-19) may lead to the infection of operators and medical staff. To date, there are no established methods of infection control. The aim of this study was to provide helpful and useful information regarding tracheostomy during the COVID-19 pandemic. PATIENTS AND METHODS: We performed a retrospective analysis on 12 patients with severe COVID-19 who were intubated and underwent tracheostomy in our hospital. RESULTS: Percutaneous tracheostomy was performed in eight cases, and open tracheostomy was performed in four cases. Open tracheostomy in the operating room was performed under a negative pressure closed-space system using a surgical drape to prevent aerosolization. CONCLUSION: Our experience suggests that bedside percutaneous tracheostomy may be a useful option in patients with COVID-19. In cases where percutaneous tracheostomy is anticipated to be difficult, open tracheostomy using a negative pressure closure may be useful in preventing aerosolization and reducing the risk of infection of healthcare workers.


Asunto(s)
Infecciones por Coronavirus/terapia , Intubación/métodos , Pandemias , Neumonía Viral/terapia , Traqueostomía/métodos , Adulto , Anciano , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Viral/patología , Neumonía Viral/virología
10.
Sci Rep ; 10(1): 18926, 2020 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33144676

RESUMEN

To explore the possibility of predicting the clinical types of Corona-Virus-Disease-2019 (COVID-19) pneumonia by analyzing the non-focus area of the lung in the first chest CT image of patients with COVID-19 by using automatic machine learning (Auto-ML). 136 moderate and 83 severe patients were selected from the patients with COVID-19 pneumonia. The clinical and laboratory data were collected for statistical analysis. The texture features of the Non-focus area of the first chest CT of patients with COVID-19 pneumonia were extracted, and then the classification model of the first chest CT of COVID-19 pneumonia was constructed by using these texture features based on the Auto-ML method of radiomics, The area under curve(AUC), true positive rate(TPR), true negative rate (TNR), positive predictive value(PPV) and negative predictive value (NPV) of the operating characteristic curve (ROC) were used to evaluate the accuracy of the first chest CT image classification model in patients with COVID-19 pneumonia. The TPR, TNR, PPV, NPV and AUC of the training cohort and test cohort of the moderate group and the control group, the severe group and the control group, the moderate group and the severe group were all greater than 95% and 0.95 respectively. The non-focus area of the first CT image of COVID-19 pneumonia has obvious difference in different clinical types. The AUTO-ML classification model of Radiomics based on this difference can be used to predict the clinical types of COVID-19 pneumonia.


Asunto(s)
Infecciones por Coronavirus/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Aprendizaje Automático , Neumonía Viral/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Infecciones por Coronavirus/patología , Femenino , Humanos , Pulmón/patología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/patología
11.
ACS Chem Neurosci ; 11(22): 3704-3706, 2020 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-33147014

RESUMEN

Postinfection complications of coronavirus disease 2019 (COVID-19) are still unknown, and one of the long-term concerns in infected people are brain pathologies. The question is that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may be an environmental factor in accelerating the sporadic neurodegeneration in the infected population. In this regard, induction of protein aggregation in the brain by SARS-CoV-2 intact structure or a peptide derived from spike protein subunits needs to be considered in futures studies. In this paper, we discuss these possibilities using pieces of evidence from other viruses.


Asunto(s)
Betacoronavirus/metabolismo , Encéfalo/metabolismo , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/metabolismo , Neumonía Viral/complicaciones , Neumonía Viral/metabolismo , Agregado de Proteínas/fisiología , Encéfalo/patología , Encéfalo/virología , Infecciones por Coronavirus/patología , Humanos , Pandemias , Neumonía Viral/patología , Factores de Tiempo
12.
PLoS One ; 15(11): e0241663, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33147270

RESUMEN

BACKGROUND/AIM: The coronavirus disease 2019 (COVID-19) had become a big threat worldwide. Liver injury is not uncommon in patients with COVID-19, and clarifying its characteristics is needed. This study aimed to identify factors associated with liver injury and to develop a new classification of predictive severity in patients with COVID-19. METHODS: Confirmed patients with COVID-19 (n = 60) were recruited retrospectively from Musashino Red Cross Hospital. The factors of liver injury especially on the elevation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were analyzed. Grading was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: During a median hospitalization follow-up of 15 (4-41) days, 51 (85.0%) patients had COVID-19 pneumonia. In clinical courses, oxygenation was needed for 25 (41.6%) patients and intubation was needed for 9 (15.0%) patients. A total of 27 (45.0%) patients had gastrointestinal symptoms (GS), such as appetite loss, diarrhea, and nausea. A logistic regression analysis revealed that C-reactive protein (CRP) at baseline, oxygenation, intubation, and GS were significant factors of liver injury. Based on these results, patients were classified into three groups: group 1, no oxygenation pneumonia; group 2, pneumonia with oxygenation or GS; and group 3, intubation. We classified 25 (41.7%), 26 (43.3%), and 9 (15.0%) patients into mild, moderate, and severe groups, respectively. The peak of AST and ALT levels was significantly stratified with this criteria (mild [median AST, 28 IU/L; median ALT, 33 IU/L], moderate [median AST, 48 IU/L; median ALT, 47.5 IU/L], and severe [median AST, 109 IU/L; median ALT, 106 IU/L]; P<0.001 and P = 0.0114, respectively). CONCLUSION: COVID-19-related liver injury was significantly stratified based on GS and severity of pneumonia.


Asunto(s)
Infecciones por Coronavirus/patología , Enfermedades del Sistema Digestivo/patología , Enfermedades del Sistema Digestivo/virología , Hepatopatías/patología , Hepatopatías/virología , Neumonía Viral/patología , Neumonía/patología , Neumonía/virología , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismo , Proteína C-Reactiva/metabolismo , Enfermedades del Sistema Digestivo/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Hígado/metabolismo , Hígado/patología , Hígado/virología , Hepatopatías/metabolismo , Masculino , Persona de Mediana Edad , Pandemias , Neumonía/metabolismo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
13.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(10): 941-947, 2020 Oct.
Artículo en Chino | MEDLINE | ID: mdl-33148390

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection would stimulate human immune system, trigger the activation and aggregation of various immune cells, and lead to the secretion of a large number of chemokines and cytokines, including interleukin 6 (IL-6), IL-10, granulocyte colony-stimulating factor (G-CSF), interferon γ (IFN-γ), tumor necrosis factor γ (TNF-γ), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 10 (CXCL10) and other cytokines. The development of uncontrolled systemic inflammatory response is a key factor in patients with critical COVID-19. Mild patients have milder inflammation and mild symptoms, but the lung inflammation in critical ones is more severe: the inflammatory factor expression levels are abnormally high; the infiltration of lung inflammatory cells is obvious along with the histopathological changes of viral pneumonia and inflammatory pneumonia. Continuous immunity response causes the accumulation of lung fibrin, permeability change, injury of the pulmonary blood vessels, and ultimately destroys the lung structure and affects ventilation and circulatory function of the lung. Therefore, continuous and severe inflammation is closely related to acute respiratory distress syndrome, multiple organ dysfunction syndrome, and disseminated intravascular coagulation in critical COVID-19 patients, which is the key point for the transition from mild to critical patients.


Asunto(s)
Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/virología , Neumonía Viral/inmunología , Betacoronavirus , Infecciones por Coronavirus/patología , Citocinas , Humanos , Pandemias , Neumonía Viral/patología
14.
Front Immunol ; 11: 583373, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33149733

RESUMEN

Coronaviruses (CoVs) are members of the genus Betacoronavirus and the Coronaviridiae family responsible for infections such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and more recently, coronavirus disease-2019 (COVID-19). CoV infections present mainly as respiratory infections that lead to acute respiratory distress syndrome (ARDS). However, CoVs, such as COVID-19, also present as a hyperactivation of the inflammatory response that results in increased production of inflammatory cytokines such as interleukin (IL)-1ß and its downstream molecule IL-6. The inflammasome is a multiprotein complex involved in the activation of caspase-1 that leads to the activation of IL-1ß in a variety of diseases and infections such as CoV infection and in different tissues such as lungs, brain, intestines and kidneys, all of which have been shown to be affected in COVID-19 patients. Here we review the literature regarding the mechanism of inflammasome activation by CoV infection, the role of the inflammasome in ARDS, ventilator-induced lung injury (VILI), and Disseminated Intravascular Coagulation (DIC) as well as the potential mechanism by which the inflammasome may contribute to the damaging effects of inflammation in the cardiac, renal, digestive, and nervous systems in COVID-19 patients.


Asunto(s)
Caspasa 1/metabolismo , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Síndrome de Liberación de Citoquinas/patología , Inflamasomas/inmunología , Neumonía Viral/inmunología , Neumonía Viral/patología , Betacoronavirus/inmunología , Coagulación Intravascular Diseminada/patología , Humanos , Inflamación/patología , Interleucina-1beta/metabolismo , Pandemias , Síndrome Respiratorio Agudo Grave/patología , Lesión Pulmonar Inducida por Ventilación Mecánica/patología
15.
Int J Mol Sci ; 21(21)2020 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-33153161

RESUMEN

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.


Asunto(s)
Plaquetas/patología , Enfermedades Cardiovasculares/virología , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/patología , Eritrocitos/patología , Ferritinas/sangre , Selectina-P/sangre , Neumonía Viral/sangre , Neumonía Viral/patología , Betacoronavirus/aislamiento & purificación , Coagulación Sanguínea/fisiología , Plaquetas/virología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/patología , Infecciones por Coronavirus/virología , Eritrocitos/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/virología , Trombosis/patología , Trombosis/virología
16.
Indian J Med Microbiol ; 38(3 & 4): 261-264, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33154233

RESUMEN

Although children with novel coronavirus infection (COVID-19) typically present with fever and respiratory symptoms, some children have reported gastrointestinal (GI) symptoms including vomiting and diarrhoea during the course of the disease. The continuous positive detection of the viral RNA from faeces in children even after nasopharyngeal swabs turned negative suggests that the GI tract may shed virus and a tentative faecal-oral transmission. The presence of angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2, which are the key proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry process, in the GI tract can explain the digestive symptoms in COVID-19. COVID-19 has implications for the management of children with chronic luminal diseases. There is increasing concern regarding the risk that children with inflammatory bowel disease being infected with SARS-CoV-2.


Asunto(s)
Infecciones por Coronavirus/patología , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/patología , Tracto Gastrointestinal/patología , Neumonía Viral/patología , Betacoronavirus , Niño , Infecciones por Coronavirus/diagnóstico , Heces/virología , Microbioma Gastrointestinal/fisiología , Tracto Gastrointestinal/microbiología , Humanos , Enfermedades Inflamatorias del Intestino/patología , Pandemias , Neumonía Viral/diagnóstico , ARN Viral/aislamiento & purificación
17.
IEEE Trans Med Imaging ; 39(8): 2615-2625, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-33156775

RESUMEN

Accurate and rapid diagnosis of COVID-19 suspected cases plays a crucial role in timely quarantine and medical treatment. Developing a deep learning-based model for automatic COVID-19 diagnosis on chest CT is helpful to counter the outbreak of SARS-CoV-2. A weakly-supervised deep learning framework was developed using 3D CT volumes for COVID-19 classification and lesion localization. For each patient, the lung region was segmented using a pre-trained UNet; then the segmented 3D lung region was fed into a 3D deep neural network to predict the probability of COVID-19 infectious; the COVID-19 lesions are localized by combining the activation regions in the classification network and the unsupervised connected components. 499 CT volumes were used for training and 131 CT volumes were used for testing. Our algorithm obtained 0.959 ROC AUC and 0.976 PR AUC. When using a probability threshold of 0.5 to classify COVID-positive and COVID-negative, the algorithm obtained an accuracy of 0.901, a positive predictive value of 0.840 and a very high negative predictive value of 0.982. The algorithm took only 1.93 seconds to process a single patient's CT volume using a dedicated GPU. Our weakly-supervised deep learning model can accurately predict the COVID-19 infectious probability and discover lesion regions in chest CT without the need for annotating the lesions for training. The easily-trained and high-performance deep learning algorithm provides a fast way to identify COVID-19 patients, which is beneficial to control the outbreak of SARS-CoV-2. The developed deep learning software is available at https://github.com/sydney0zq/covid-19-detection.


Asunto(s)
Infecciones por Coronavirus/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Pulmón/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Aprendizaje Automático Supervisado , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus , Niño , Infecciones por Coronavirus/patología , Femenino , Humanos , Pulmón/patología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/patología , Estudios Retrospectivos , Tórax/diagnóstico por imagen , Adulto Joven
18.
Cell Death Dis ; 11(11): 957, 2020 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-33159040

RESUMEN

A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases1. Age represents a key factor in COVID-19 morbidity and mortality2. Understanding age-associated immune signatures of patients are therefore important to identify preventive and therapeutic strategies. In this study, we investigated the immune profile of COVID-19 hospitalized patients identifying a distinctive age-dependent immune signature associated with disease severity. Indeed, defined circulating factors - CXCL8, IL-10, IL-15, IL-27, and TNF-α - positively correlate with older age, longer hospitalization, and a more severe form of the disease and may thus represent the leading signature in critical COVID-19 patients.


Asunto(s)
Infecciones por Coronavirus/patología , Citocinas/metabolismo , Neumonía Viral/patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Betacoronavirus/aislamiento & purificación , Análisis por Conglomerados , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Femenino , Humanos , Inmunoglobulina G/sangre , Interleucina-10/metabolismo , Interleucina-8/metabolismo , Tiempo de Internación , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/virología , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/metabolismo
20.
PLoS One ; 15(11): e0240784, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33166287

RESUMEN

Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (67/128; 52.3%) at median of 10 weeks after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.


Asunto(s)
Infecciones por Coronavirus/patología , Fatiga/etiología , Neumonía Viral/patología , Adulto , Anciano , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/virología , Fatiga/epidemiología , Femenino , Humanos , Subunidad alfa del Receptor de Interleucina-2/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/virología , Prevalencia , Índice de Severidad de la Enfermedad
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