The race to outpace severe acute respiratory syndrome (SARS).
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ABSTRACT:
SUBMITTER: Patrick DM
PROVIDER: S-EPMC154183 | biostudies-literature | 2003 May
REPOSITORIES: biostudies-literature
Publications
The race to outpace severe acute respiratory syndrome (SARS).
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20030501 10
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Project description:Severe acute respiratory syndrome (SARS) is a new human disease caused by an animal coronavirus that adapted to efficient human-to-human transmission. The disease first emerged in November 2002 in Guangdong Province, China and spread globally within months. The SARS coronavirus (SARS CoV) affects multiple organ systems with severe viral pneumonia as its main clinical manifestation but with diarrhea, lymphopenia, and mild liver dysfunction being common extra-pulmonary manifestations. Increasing age and the presence of underlying respiratory diseases worsens the prognosis. Unlike other respiratory viral infections, transmission of SARS was less frequent in the first 5 days of illness and correlated with low viral load in the upper respiratory tract at this stage of the illness. This fortuitous feature of the disease allowed the public health measures of case detection and patient isolation to interrupt virus transmission in the community and abort the SARS outbreak. Bats are a reservoir of a virus closely related to SARS CoV and this may be the likely precursor from which the human-adapted SARS CoV emerged. Small mammals such as ‘civet-cats’ (Paguma larvata) within live animal markets in southern China serve as amplifiers of infection and these markets were the likely interface where zoonotic transmission occurred. The viral spike protein is necessary and sufficient for inducing protective antibody responses and has been a key target in the development of candidate vaccines.
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Project description:We used cDNA microarrays to systematically analyze host responses in SARS-infected individuals from onset of symptoms to discharge from hospital or death. We modeled gene expression in 60 datasets from 40 unique patients of varied clinical evolution with emphasis on correlating innate and adaptive immune responses with discrete clinical phases of the disease. Keywords: Comparative patient class comparision, SARS patients relative to healthy controls
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Project description:Three major human coronavirus disease outbreaks, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and 2019 coronavirus disease (COVID-19), occurred in the twenty-first century and were caused by different coronaviruses (CoVs). All these viruses are considered to have originated from bats and transmitted to humans through intermediate hosts. SARS-CoV-1 and SARS-CoV-2, disease agent of COVID-19, shared around 80% genomic similarity, and thus belong to SARS-related CoVs. As a natural reservoir of viruses, bats harbor numerous other SARS-related CoVs that could potentially infect humans around the world, causing SARS or COVID-19 like outbreaks in the future. In this review, we summarized the current knowledge of CoVs on geographical distribution, genetic diversity, cross-species transmission potential and possible pathogenesis in humans, aiming for a better understanding of bat SARS-related CoVs in the context of prevention and control.
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Project description:The 3C-like proteinase (3CL(pro)) of the severe acute respiratory syndrome (SARS) coronavirus plays a vital role in virus maturation and is proposed to be a key target for drug design against SARS. Various in vitro studies revealed that only the dimer of the matured 3CL(pro) is active. However, as the internally encoded 3CL(pro) gets matured from the replicase polyprotein by autolytic cleavage at both the N-terminal and the C-terminal flanking sites, it is unclear whether the polyprotein also needs to dimerize first for its autocleavage reaction. We constructed a large protein containing the cyan fluorescent protein (C), the N-terminal flanking substrate peptide of SARS 3CL(pro) (XX), SARS 3CL(pro) (3CLP), and the yellow fluorescent protein (Y) to study the autoprocessing of 3CL(pro) using fluorescence resonance energy transfer. In contrast to the matured 3CL(pro), the polyprotein, as well as the one-step digested product, 3CLP-Y-His, were shown to be monomeric in gel filtration and analytic ultracentrifuge analysis. However, dimers can still be induced and detected when incubating these large proteins with a substrate analog compound in both chemical cross-linking experiments and analytic ultracentrifuge analysis. We also measured enzyme activity under different enzyme concentrations and found a clear tendency of substrate-induced dimer formation. Based on these discoveries, we conclude that substrate-induced dimerization is essential for the activity of SARS-3CL(pro) in the polyprotein, and a modified model for the 3CL(pro) maturation process was proposed. As many viral proteases undergo a similar maturation process, this model might be generally applicable.
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Project description:From early March 2003 to late May 2003, severe acute respiratory syndrome (SARS) was detected in Singapore. The increase in workload and new infection control procedures were thought to affect resuscitation and airway management. Our aim was to study the effects of wearing of personal protective equipment (PPE) and powered air-purifying respirator (PAPR) and the restriction in the number of resuscitation personnel on airway management during the SARS crisis. Data was collected prospectively through an ongoing emergency airway registry. The data was divided into three periods: (1) before PPE was instituted from 1 November 2002 to 31 March 2003; (2) during SARS (when PPE use was mandatory) from 1 April to 31 July 2003; (3) post-SARs (when PPE use was non-mandatory but encouraged) from 1 August to 31 March 2004. There was no change in patient demographics during the three periods. There were significant increases in the proportion of resuscitation cases and airway interventions during the SARS period compared to the pre-SARS period. The resident medical officer intubation rate decreased from 45.1% pre-SARS to 35.2% during SARS and 17.7% post-SARS. The complication rates were 10.5%, 9.9% and 9.4% in periods 1-3, respectively. Restriction in the number of healthcare staff attending to each patient may have influenced the department's decision to allow only the most confident or experienced personnel to manage the airway. The exposure of junior medical officers in emergency airway management during SARS and the immediate post-SARS period was decreased. This trend should be monitored further and intervention may be necessary should it continue to decline.
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