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1.
J Infect Chemother ; 27(1): 70-75, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32950393

RESUMO

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.


Assuntos
Infecções Assintomáticas/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Eliminação de Partículas Virais , Adulto , Fatores Etários , Idoso , Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
2.
Ann Lab Med ; 41(2): 129-138, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33063674

RESUMO

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.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/patologia , Variação Genética , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Suscetibilidade a Doenças , Expressão Gênica , Humanos , Pandemias , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Índice de Gravidade de Doença
3.
Am J Hum Genet ; 108(1): 194-201, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33357513

RESUMO

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.


Assuntos
/complicações , Interações Hospedeiro-Patógeno/genética , Pneumonia Viral/complicações , Pneumonia Viral/genética , Bronquite/genética , /fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Bases de Dados Genéticas , Registros Eletrônicos de Saúde , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Hemoglobinas/genética , Humanos , Pacientes Internados , Desequilíbrio de Ligação , Masculino , Pacientes Ambulatoriais , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética , Análise de Componente Principal , Doença Pulmonar Obstrutiva Crônica/genética , Reprodutibilidade dos Testes , Reino Unido
4.
BMC Infect Dis ; 20(1): 961, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334317

RESUMO

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.


Assuntos
/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , /patologia , Criança , China/epidemiologia , Feminino , Coração/fisiopatologia , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
5.
PLoS One ; 15(12): e0243598, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315903

RESUMO

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.


Assuntos
/tratamento farmacológico , Cloroquina/uso terapêutico , Pandemias , /patogenicidade , Adolescente , Adulto , Idoso , Antivirais/efeitos adversos , Antivirais/uso terapêutico , /patologia , Cloroquina/efeitos adversos , Cloroquina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Adulto Jovem
6.
Rev. Hosp. Ital. B. Aires (2004) ; 40(4): 227-232, dic. 2020. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1145596

RESUMO

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)


Assuntos
Humanos , Feminino , Pneumonia Viral/complicações , Infecções por Coronavirus/complicações , Contracepção Hormonal/métodos , Pneumonia Viral/patologia , Gravidez não Desejada , Infecções por Coronavirus/patologia , Anticoncepcionais/administração & dosagem , Anticoncepcionais/classificação , Anticoncepcionais/provisão & distribução , Direitos Sexuais e Reprodutivos , Coagulação Intravascular Disseminada/etiologia , Tromboembolia Venosa/etiologia , Pandemias , Betacoronavirus , Acesso aos Serviços de Saúde
7.
Indian J Med Microbiol ; 38(3 & 4): 252-260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154232

RESUMO

The world is challenged with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic. Although preventive measures such as social distancing, personal protective equipment and isolation would decrease the spread of the infection, a definitive treatment is still under way. Antivirals, immunisation, convalescent plasma (CP) and many more modalities are under trial, and there has been no definite answer to the management of COVID-19 infection. All patients so far have received the standard and symptomatic care. It is shown that the SARS-CoV 2 is a respiratory pathogen, and 80% of the infected patients would recover from the illness and it is the 20% of the infected patients require hospitalisation and even critical care. CP has been used to treat recent epidemic respiratory infections such as Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) infections with promising results. The CP of a recovered individual contains antibodies which neutralise the virus and decrease the viral replication in the patient. It is a classic adaptive immunotherapy and has been applied in the prevention and treatment of many infectious diseases. CP is plasma taken from a person who has recovered from an infection, which contains neutralising antibodies against the said infection. Giving CP to susceptible individuals or infected patients is a form of passive antibody therapy and in the case of SARS-CoV-2, is expected to provide protection by viral neutralisation and antibody-dependent cytotoxicity and phagocytosis. The adaptive response is to a specific antigen-binding array of molecules that are foreign to the host. The human response to viruses uses both the innate and the adaptive arms in its attempt to rid the host of the invading pathogen. The humoral response is a component of the adaptive immune response that allows for antibodies to bind to foreign invading pathogens, marks the pathogens and their toxins for phagocytosis and recruits further phagocytic cells to the site via the activation of the complement system and eventually prevents the pathogen from infecting target cells. Studies from Wuhan from various institutions during the research on COVID-19 infections during December 2019 have also shown promising results. Till date, randomised controlled studies for the use of CP in SARS-CoV-2 infection are lacking, and many countries have invited institutions to participate in clinical trials. The Indian Council of Medical research and the Central Drugs Standard Control Organisation, Government of India, have allowed the use of CP as an investigational drug under a trial basis. Internationally, agencies such as the USFDA, American Association of Blood Banks, European Blood Safety and British Blood Transfusion Society have also come out with various guidelines for the use of CP in COVID-19 infection. This article will review the current guidelines for the use of CP and compare the various guidelines of different agencies.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Infecções por Coronavirus/terapia , Imunoterapia/métodos , Pneumonia Viral/terapia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Feminino , Guias como Assunto , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/métodos , Masculino , Testes de Neutralização , Pandemias , Pneumonia Viral/patologia , Glicoproteína da Espícula de Coronavírus/imunologia
8.
Indian J Med Microbiol ; 38(3 & 4): 261-264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154233

RESUMO

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.


Assuntos
Infecções por Coronavirus/patologia , Gastroenteropatias/diagnóstico , Gastroenteropatias/patologia , Trato Gastrointestinal/patologia , Pneumonia Viral/patologia , Betacoronavirus , Criança , Infecções por Coronavirus/diagnóstico , Fezes/virologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Humanos , Doenças Inflamatórias Intestinais/patologia , Pandemias , Pneumonia Viral/diagnóstico , RNA Viral/isolamento & purificação
9.
Open Biol ; 10(11): 200213, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33171068

RESUMO

COVID-19 pandemic has caused a global lockdown in many countries throughout the world. Faced with a new reality, and until a vaccine or efficient treatment is found, humanity must figure out ways to keep the economy going, on one hand, while keeping the population safe, on the other hand, especially those that are susceptible to this virus. Here, we use a Watts-Strogatz network simulation, with parameters that were drawn from what is already known about the virus, to explore five different scenarios of partial lockdown release in two geographical locations with different age distributions. We find that separating age groups by reducing interactions between them protects the general population and reduces mortality rates. Furthermore, the addition of new connections within the same age group to compensate for the lost connections outside the age group still has a strong beneficial influence and reduces the total death toll by about 62%. While complete isolation from society may be the most protective scenario for the elderly population, it would have an emotional and possibly cognitive impact that might outweigh its benefit. Therefore, we propose creating age-related social recommendations or even restrictions, thereby allowing social connections while still offering strong protection for the older population.


Assuntos
Simulação por Computador , Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adolescente , Adulto , Fatores Etários , Betacoronavirus/isolamento & purificação , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Lactente , Recém-Nascido , Israel/epidemiologia , Itália/epidemiologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Adulto Jovem
10.
EBioMedicine ; 61: 103104, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33158808

RESUMO

BACKGROUND: COVID-19 is a deadly pulmonary disease with peculiar characteristics, which include variable clinical course and thrombophilia. A thorough understanding of the pathological correlates of the disease is still missing. METHODS: Here we report the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. Histological analysis is complemented by immunohistochemistry for cellular and viral antigens and the detection of viral genomes by in situ RNA hybridization. FINDINGS: COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%). Thrombi were in different stages of organization, consistent with their local origin. Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease. An additional feature was the common presence of a large number of dysmorphic pneumocytes, often forming syncytial elements (36/41, 87%). Despite occasional detection of virus-positive cells, no overt signs of viral infection were detected in other organs, which showed non-specific alterations. INTERPRETATION: COVID-19 is a unique disease characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia. Several of COVID-19 features might be consequent to the persistence of virus-infected cells for the duration of the disease. FUNDING: This work was supported by a King's Together Rapid COVID-19 Call grant from King's College London. MG is supported by the European Research Council (ERC) Advanced Grant 787971 "CuRE" and by Programme Grant RG/19/11/34633 from the British Heart Foundation.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , RNA Viral/metabolismo , Trombose/etiologia , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais Alveolares/citologia , Células Epiteliais Alveolares/virologia , Autopsia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Cuidados Críticos , Células Endoteliais/virologia , Feminino , Células Gigantes/citologia , Células Gigantes/virologia , Humanos , Pulmão/patologia , Pulmão/virologia , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo
11.
Sci Rep ; 10(1): 18926, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144676

RESUMO

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.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Aprendizado de Máquina , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Infecções por Coronavirus/patologia , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia
12.
Sci Rep ; 10(1): 19630, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184506

RESUMO

The novel coronavirus SARS-CoV-2 causes COVID-19, a highly pathogenic viral infection threatening millions. The majority of the individuals infected are asymptomatic or mildly symptomatic showing typical clinical signs of common cold. However, approximately 20% of the patients can progress to acute respiratory distress syndrome (ARDS), evolving to death in about 5% of cases. Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for virus entry into host target cells. The upregulation of ACE2 in patients with comorbidities may represent a propensity for increased viral load and spreading of infection to extrapulmonary tissues. This systemic infection is associated with higher neutrophil to lymphocyte ratio in infected tissues and high levels of pro-inflammatory cytokines leading to an extensive microthrombus formation with multiorgan failure. Herein we investigated whether SARS-CoV-2 can stimulate extracellular neutrophils traps (NETs) in a process called NETosis. We demonstrated for the first time that SARS-CoV-2 in fact is able to activate NETosis in human neutrophils. Our findings indicated that this process is associated with increased levels of intracellular Reactive Oxygen Species (ROS) in neutrophils. The ROS-NET pathway plays a role in thrombosis formation and our study suggest the importance of this target for therapy approaches against disease.


Assuntos
Infecções por Coronavirus/imunologia , Armadilhas Extracelulares/metabolismo , Neutrófilos/citologia , Pneumonia Viral/imunologia , Adolescente , Idoso , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pandemias , Fagocitose , Pneumonia Viral/patologia , Espécies Reativas de Oxigênio/metabolismo
13.
Cells ; 9(11)2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33202960

RESUMO

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was declared a pandemic by the WHO on 19 March 2020. This pandemic is associated with markedly elevated blood glucose levels and a remarkable degree of insulin resistance, which suggests pancreatic islet ß-cell dysfunction or apoptosis and insulin's inability to dispose of glucose into cellular tissues. Diabetes is known to be one of the top pre-existing co-morbidities associated with the severity of COVID-19 along with hypertension, cardiocerebrovascular disease, advanced age, male gender, and recently obesity. This review focuses on how COVID-19 may be responsible for the accelerated development of type 2 diabetes mellitus (T2DM) as one of its acute and suspected long-term complications. These observations implicate an active role of metabolic syndrome, systemic and tissue islet renin-angiotensin-aldosterone system, redox stress, inflammation, islet fibrosis, amyloid deposition along with ß-cell dysfunction and apoptosis in those who develop T2DM. Utilizing light and electron microscopy in preclinical rodent models and human islets may help to better understand how COVID-19 accelerates islet and ß-cell injury and remodeling to result in the long-term complications of T2DM.


Assuntos
Apoptose , Infecções por Coronavirus/patologia , Diabetes Mellitus Tipo 2/patologia , Pneumonia Viral/patologia , Animais , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 2/complicações , Humanos , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Síndrome Metabólica/complicações , Síndrome Metabólica/patologia , Estresse Oxidativo , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Sistema Renina-Angiotensina/fisiologia
14.
Nat Commun ; 11(1): 5859, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203833

RESUMO

The outbreak of COVID-19 has become a worldwide pandemic. The pathogenesis of this infectious disease and how it differs from other drivers of pneumonia is unclear. Here we analyze urine samples from COVID-19 infection cases, healthy donors and non-COVID-19 pneumonia cases using quantitative proteomics. The molecular changes suggest that immunosuppression and tight junction impairment occur in the early stage of COVID-19 infection. Further subgrouping of COVID-19 patients into moderate and severe types shows that an activated immune response emerges in severely affected patients. We propose a two-stage mechanism of pathogenesis for this unusual viral infection. Our data advance our understanding of the clinical features of COVID-19 infections and provide a resource for future mechanistic and therapeutics studies.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Betacoronavirus/patogenicidade , Biomarcadores/urina , Infecções por Coronavirus/urina , Progressão da Doença , Humanos , Tolerância Imunológica , Pandemias , Pneumonia/imunologia , Pneumonia/patologia , Pneumonia/urina , Pneumonia Viral/urina , Proteoma/análise , Junções Íntimas/patologia
15.
Nat Commun ; 11(1): 5838, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203860

RESUMO

Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Fator de Transcrição STAT2/metabolismo , Transdução de Sinais , Animais , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Cricetinae , Imunidade Inata , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Pulmão/patologia , Pulmão/virologia , Camundongos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Fator de Transcrição STAT2/genética , Replicação Viral
16.
Int J Mol Sci ; 21(22)2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207699

RESUMO

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target. To date, the present study provides the largest untargeted metabolomics and lipidomics analysis of plasma from COVID-19 patients and control groups, identifying new mechanisms associated with the host response to COVID-19, potential plasma biomarkers, and therapeutic targets.


Assuntos
Infecções por Coronavirus/metabolismo , Metaboloma , Pneumonia Viral/metabolismo , Idoso , Idoso de 80 Anos ou mais , Aminoácidos/sangue , Ácido Araquidônico/sangue , Biomarcadores/sangue , Ciclo do Ácido Cítrico , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Feminino , Gluconeogênese , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Oleico/sangue , Pandemias , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Fosfolipases A2/sangue , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Triglicerídeos/sangue
17.
J Forensic Leg Med ; 76: 102036, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33208233

RESUMO

The COVID-19 pandemic has forced forensic practitioners to consider how we perform our normal duties, especially when those duties involve humans. The potential for contracting the virus from working in close contact with living sufferers is high, and we have yet to fully determine the risk of infection from the deceased. In an attempt to support the community, the Journal of Forensic & Legal Medicine has drawn together three articles which underline the importance of continued forensic medical practice during the pandemic and highlight some factors to consider in a Roadmap towards safe practice. Our Roadmap has intentionally taken an international perspective and supports other work we have published in the Journal on our collective response to the COVID-19 crisis.


Assuntos
Betacoronavirus , Infecções por Coronavirus/patologia , Controle de Infecções/organização & administração , Práticas Mortuárias/organização & administração , Equipamento de Proteção Individual/estatística & dados numéricos , Pneumonia Viral/patologia , Contenção de Riscos Biológicos/métodos , Infecções por Coronavirus/prevenção & controle , Medicina Legal/organização & administração , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle
18.
BMC Infect Dis ; 20(1): 859, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213360

RESUMO

BACKGROUND: Efficient control and management in the ongoing COVID-19 pandemic needs to carefully balance economical and realizable interventions. Simulation models can play a cardinal role in forecasting possible scenarios to sustain decision support. METHODS: We present a sophisticated extension of a classical SEIR model. The simulation tool CovidSIM Version 1.0 is an openly accessible web interface to interactively conduct simulations of this model. The simulation tool is used to assess the effects of various interventions, assuming parameters that reflect the situation in Austria as an example. RESULTS: Strict contact reduction including isolation of infected persons in quarantine wards and at home can substantially delay the peak of the epidemic. Home isolation of infected individuals effectively reduces the height of the peak. Contact reduction by social distancing, e.g., by curfews, sanitary behavior, etc. are also effective in delaying the epidemic peak. CONCLUSIONS: Contact-reducing mechanisms are efficient to delay the peak of the epidemic. They might also be effective in decreasing the peak number of infections depending on seasonal fluctuations in the transmissibility of the disease.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Interface Usuário-Computador , Áustria/epidemiologia , Betacoronavirus/isolamento & purificação , Simulação por Computador , Busca de Comunicante , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Quarentena
19.
BMC Infect Dis ; 20(1): 862, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213364

RESUMO

BACKGROUND: The speed and reach of the COVID-19 pandemic has created special scenarios to be considered, such as those in where patients who meet criteria for hospitalization due to moderate/severe disease cannot be hospitalized due to economic constraints and saturation of national health systems. The aim of this report is to present an unusual case of a severe COVID-19 patient managed at home in a developing country, and to discuss some of the available guidelines and potential therapeutic options for this type of cases. CASE PRESENTATION: A 60-year-old female seeking medical attention through teleconsultation presents with profound dyspnea, oppressive chest pain, fatigue, episodic hallucinations, and difficulty sleeping, for what she originally sought medical attention at an ER but could not be admitted due to saturation of the health system. A positive PCR test for COVID-19, and a CT scan of the chest showing bilateral consolidations with ground-glass opacities confirmed the diagnosis. The patient was managed at home, with corticosteroids, nitazoxanide and a single dose of 40 mg of subcutaneous enoxaparin. Colchicine was added at the third day of treatment. Standard oxygen therapy through nasal cannula was also recommended. Daily follow-ups were established to monitor for signs of clinical improvement. Two weeks later from the initial consultation the patient presents marked improvement in her symptoms, as well as in her CT scan, which prompted in discontinuation of the medications and the oxygen therapy. CONCLUSIONS: There are several limitations in this report regarding the clinical data and the management, but such limitations do also reflect the state of emergency and the chaos that resides in the health care systems of developing nations. For the ambulatory care of COVID-19 patients, several aspects of disease management may differ from current guidelines and basic requirements may represent a huge challenge to cover. Further research is needed to assist physicians in the daily clinical decision making, to optimize patient outcomes, and to reduce the probability of adverse scenarios of patients with COVID-19 managed in the ambulatory setting.


Assuntos
Assistência Ambulatorial , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Corticosteroides/uso terapêutico , Antiparasitários , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Enoxaparina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Telemedicina , Tiazóis/uso terapêutico , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X
20.
BMC Infect Dis ; 20(1): 860, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213370

RESUMO

BACKGROUND: The accuracy of a new optical biosensor (OB) point-of-care device for the detection of severe infections is studied. METHODS: The OB emits different wavelengths and outputs information associated with heart rate, pulse oximetry, levels of nitric oxide and kidney function. At the first phase, recordings were done every two hours for three consecutive days after hospital admission in 142 patients at high-risk for sepsis by placing the OB on the forefinger. At the second phase, single recordings were done in 54 patients with symptoms of viral infection; 38 were diagnosed with COVID-19. RESULTS: At the first phase, the cutoff value of positive likelihood of 18 provided 100% specificity and 100% positive predictive value for the diagnosis of sepsis. These were 87.5 and 91.7% respectively at the second phase. OB diagnosed severe COVID-19 with 83.3% sensitivity and 87.5% negative predictive value. CONCLUSIONS: The studied OB seems valuable for the discrimination of infection severity.


Assuntos
Técnicas Biossensoriais/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Sepse/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Área Sob a Curva , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença
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