RESUMEN
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by respiratory distress, multiorgan dysfunction, and, in some cases, death. The pathological mechanisms underlying COVID-19 respiratory distress and the interplay with aggravating risk factors have not been fully defined. Lung autopsy samples from 18 patients with fatal COVID-19, with symptom onset-to-death times ranging from 3 to 47 days, and antemortem plasma samples from 6 of these cases were evaluated using deep sequencing of SARS-CoV-2 RNA, multiplex plasma protein measurements, and pulmonary gene expression and imaging analyses. Prominent histopathological features in this case series included progressive diffuse alveolar damage with excessive thrombosis and late-onset pulmonary tissue and vascular remodeling. Acute damage at the alveolar-capillary barrier was characterized by the loss of surfactant protein expression with injury to alveolar epithelial cells, endothelial cells, respiratory epithelial basal cells, and defective tissue repair processes. Other key findings included impaired clot fibrinolysis with increased concentrations of plasma and lung plasminogen activator inhibitor-1 and modulation of cellular senescence markers, including p21 and sirtuin-1, in both lung epithelial and endothelial cells. Together, these findings further define the molecular pathological features underlying the pulmonary response to SARS-CoV-2 infection and provide important insights into signaling pathways that may be amenable to therapeutic intervention.
Asunto(s)
COVID-19 , Senescencia Celular , Fibrinólisis , Humanos , Pulmón , SARS-CoV-2RESUMEN
We need to understand and quantify the dominant variables that govern the SARS-CoV-2 outbreak, rather than relying exclusively on confirmed cases and their geospatial spread.
Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus , Interacciones Huésped-Patógeno , Difusión de la Información , Modelos Teóricos , Pandemias/prevención & control , Neumonía Viral , COVID-19 , China/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Monitoreo Epidemiológico , Europa (Continente)/epidemiología , Predicción , Humanos , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Salud Pública , Cuarentena , SARS-CoV-2 , Condiciones Sociales , Estados Unidos/epidemiologíaAsunto(s)
Bioterrorismo , Defensa Civil , Ciencias Forenses , Laboratorios/organización & administración , Medidas de Seguridad , Bioterrorismo/prevención & control , Centers for Disease Control and Prevention, U.S. , Defensa Civil/organización & administración , Dermatoglifia del ADN , Humanos , Medidas de Seguridad/organización & administración , Estados Unidos , United States Government AgenciesRESUMEN
To illustrate the usefulness of mathematical models to the microbiology and medical communities, we explain how to construct and apply a simple transmission model of an emerging pathogen. We chose to model, as a case study, a large (>8,000 reported cases) on-going outbreak of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) in the Los Angeles County Jail. A major risk factor for CA-MRSA infection is incarceration. Here, we show how to design a within-jail transmission model of CA-MRSA, parameterize the model and reconstruct the outbreak. The model is then used to assess the severity of the outbreak, predict the epidemiological consequences of a catastrophic outbreak and design effective interventions for outbreak control.
Asunto(s)
Brotes de Enfermedades , Modelos Estadísticos , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/transmisión , Humanos , Los Angeles/epidemiología , Resistencia a la Meticilina , Prisiones , Infecciones Estafilocócicas/microbiologíaRESUMEN
The World Health Organization Influenza Program is one of the best developed and longest running infectious disease surveillance systems that exists. It maintains a worldwide watch of influenza's evolution to assist delivery of appropriately formulated vaccines in time to blunt seasonal epidemics and unpredictable pandemics. Despite the program's success, however, much more is possible with today's advanced technologies. This article summarizes ongoing human influenza surveillance activities worldwide. It shows that the technology to establish a high-throughput laboratory network that can process and test influenza viruses more quickly and more accurately is available. It also emphasizes the practical public health and scientific applications of such a network.