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Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies.
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PMID:Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. 1707 15

Infection with the SARS-associated coronavirus (SARS-CoV) induces an atypical pulmonary disease with a high lethality rate. Although the initial SARS epidemic was contained, sporadic outbreaks of the disease still occur, suggesting a continuous need for a vaccine against this virus. We therefore explored exosome-based vaccines containing the spike S proteins of SARS-CoV. S-containing exosomes were obtained by replacing the transmembrane and cytoplasmic domains of the S protein by those of VSV-G. The immunogenicity and efficacy of the S-containing exosomes were tested in mice and compared to an adenoviral vector vaccine expressing the S protein. Both, S-containing exosomes and the adenoviral vector vaccine induced neutralizing antibody titers. After priming with the SARS-S exosomal vaccine and boosting with the adenoviral vector the neutralizing antibody titers exceeded those observed in the convalescent serum of a SARS patient. Both approaches were effective in a SARS-S-expressing tumor challenge model and thus warrant further investigation.
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PMID:Exosomal vaccines containing the S protein of the SARS coronavirus induce high levels of neutralizing antibodies. 1725 82

Hospital infection prevalence surveys were performed in our 1400-bed University medical centre in Hong Kong from 1985 to 1988. We investigated the rates of four major hospital-acquired infections (HAIs) (pneumonia, symptomatic urinary tract infection, surgical site infection and laboratory-confirmed bloodstream infection) in order to identify current distribution and any changes after 15 years. A one-day point prevalence study was performed on 7 September 2005. All inpatients were surveyed for HAIs, community-acquired infections (CAIs), risk factors, pathogenic isolates and antibiotics prescribed. Infections were diagnosed according to Centers for Disease Control and Prevention (CDC) criteria. In total, 1021 patients were surveyed; of these, 41 had 42 HAIs (4% prevalence) and 389 (38%) were receiving antibiotics. The commonest HAI was pneumonia (1.4%) followed by bloodstream infection (0.9%) and symptomatic urinary tract infection (0.8%). The prevalence of postoperative surgical site infection was 5.6%. The nosocomial prevalence rate was highest in the Intensive Care Unit, followed by the Pediatric and Neonatal Intensive Care Units, Children's Cancer Centre/Bone Marrow Transplant Unit and Orthopaedics with Traumatology. Meticillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were the commonest pathogens. The rates are significantly lower than previously and reflect the increased resources for infection control made available following the outbreak of severe acute respiratory syndrome (SARS).
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PMID:Prevalence of hospital infection and antibiotic use at a university medical center in Hong Kong. 1727 59

Many viruses encode antagonists to prevent interferon (IFN) induction. Infection of fibroblasts with the murine hepatitis coronavirus (MHV) and SARS-coronavirus (SARS-CoV) did not result in nuclear translocation of interferon-regulatory factor 3 (IRF3), a key transcription factor involved in IFN induction, and induction of IFN mRNA transcription. Furthermore, MHV and SARS-CoV infection could not prevent IFN induction by poly (I:C) or Sendai virus, suggesting that these CoVs do not inactivate IRF3-mediated transcription regulation, but apparently prevent detection of replicative RNA by cellular sensory molecules. Our data indicate that shielding of viral RNA to host cell sensors might be the main general mechanism for coronaviruses to prevent IFN induction.
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PMID:Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition. 1731 33

Infection is the leading cause of morbidity and mortality in immunocompromised patients such as hematopoietic/solid organ transplant recipients and individuals with human immunodeficiency virus. Community respiratory virus infections are increasingly recognized as a significant threat to these patients. This article reviews current information in the clinical field of community respiratory viruses, including several newly discovered respiratory viruses. Respiratory syncytial virus, influenza viruses, parainfluenza viruses, and adenoviruses cause the most serious disease in immunocompromised hosts, but other respiratory viruses are becoming increasingly appreciated as a cause of both upper and lower respiratory tract disease. The clinical impact of these new viruses, including human metapneumovirus, non-SARS human coronaviruses, and human bocavirus, is not yet clear. Modern molecular technology has made the discovery of new viruses possible; the use of these new technologies in direct patient care is not yet standard but is becoming increasingly utilized. Clinicians should appreciate the potential for the development of antiviral resistance to influenza antivirals in immunocompromised patients.
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PMID:Community respiratory virus infections in immunocompromised patients: hematopoietic stem cell and solid organ transplant recipients, and individuals with human immunodeficiency virus infection. 1745 76

This short-term observational study of infection control practice was performed in the medical emergency outpatient department (EMOPD) of a tertiary-care hospital in India when threatened by an outbreak of severe acute respiratory syndrome (SARS). An investigator attended the lobby daily to screen patients with symptoms for SARS. Patient/attendant load, patient flow, medical staff working practices and position in the EMOPD were observed. Infection control measures such as fumigation and cleaning were noted, as was the EMOPD laboratory function, use of personnel protection and display of information on infectious diseases. A total of 162 (7.4%) of the 2165 patients surveyed had respiratory symptoms but no cases of SARS were found. The flow of patients and their attendants was not systematic. No laboratory tests for SARS were available, and no educational material on SARS was displayed. The EMOPDs in key hospitals need be able to screen for infectious diseases, especially in view of the threats from SARS and Avian influenza.
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PMID:Preparations and limitations for prevention of severe acute respiratory syndrome in a tertiary care centre of India. 1751 34

Identification of the nature of severe acute respiratory syndrome (SARS)-infected cells is crucial toward understanding the pathogenesis. Using multicolor colocalization techniques, we previously reported that SARS(+) cells in the lung of fatally infected patients expressed the only known functional receptor, angiotensin-converting enzyme 2, and also a binding receptor, liver/lymph node-specific ICAM-3-grabbing non-integrin (CD209L). In this study, we show that SARS-infected cells also express the stem/progenitor cell markers CD34 and Oct-4, and do not express cytokeratin or surfactant. These putative lung stem/progenitor cells can also be identified in some non-SARS individuals and can be infected by SARS-coronavirus ex vivo. Infection of these cells may contribute to the loss of lung repair capacity that leads to respiratory failure as clinically observed.
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PMID:A novel subset of putative stem/progenitor CD34+Oct-4+ cells is the major target for SARS coronavirus in human lung. 1792 1

Although the local public health response to the severe acute respiratory syndrome outbreak in Canada was critical to the diagnosis, management and treatment of patients, such a rapid research response required a national effort to engage the research and stakeholder communities. The Canadian research effort, coordinated through the Institute of Infection and Immunity of the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research, has provided insight into the mechanisms required to ensure the rapid development of strategical initiatives in response to emerging infectious diseases. It has also provided a rational basis to set up a national network to be engaged if needed in the future.
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PMID:Innovation and challenges in funding rapid research responses to emerging infectious diseases: Lessons learned from the outbreak of severe acute respiratory syndrome. 1815 88

Infection of humans with the severe acute respiratory syndrome coronavirus (SARS-CoV) results in substantial morbidity and mortality, with death resulting primarily from respiratory failure. While the lungs are the major site of infection, the brain is also infected in some patients. Brain infection may result in long-term neurological sequelae, but little is known about the pathogenesis of SARS-CoV in this organ. We previously showed that the brain was a major target organ for infection in mice that are transgenic for the SARS-CoV receptor (human angiotensin-converting enzyme 2). Herein, we use these mice to show that virus enters the brain primarily via the olfactory bulb, and infection results in rapid, transneuronal spread to connected areas of the brain. This extensive neuronal infection is the main cause of death because intracranial inoculation with low doses of virus results in a uniformly lethal disease even though little infection is detected in the lungs. Death of the animal likely results from dysfunction and/or death of infected neurons, especially those located in cardiorespiratory centers in the medulla. Remarkably, the virus induces minimal cellular infiltration in the brain. Our results show that neurons are a highly susceptible target for SARS-CoV and that only the absence of the host cell receptor prevents severe murine brain disease.
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PMID:Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. 1849 71

The newly emergent human coronavirus HKU1 (HCoV-HKU1) was first identified in Hong Kong in 2005. Infection by HCoV-HKU1 occurs worldwide and causes syndromes such as the common cold, bronchitis, and pneumonia. The CoV main protease (M(pro)), which is a key enzyme in viral replication via the proteolytic processing of the replicase polyproteins, has been recognized as an attractive target for rational drug design. In this study, we report the structure of HCoV-HKU1 M(pro) in complex with a Michael acceptor, inhibitor N3. The structure of HCoV-HKU1 provides a high-quality model for group 2A CoVs, which are distinct from group 2B CoVs such as severe acute respiratory syndrome CoV. The structure, together with activity assays, supports the relative conservation at the P1 position that was discovered by sequencing the HCoV-HKU1 genome. Combined with structural data from other CoV M(pro)s, the HCoV-HKU1 M(pro) structure reported here provides insights into both substrate preference and the design of antivirals targeting CoVs.
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PMID:Structure of the main protease from a global infectious human coronavirus, HCoV-HKU1. 1856 31


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