Articles: sars-cov-2.
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Tragically, many of the infections and deaths recorded in the global coronavirus disease 2019 (COVID-19) pandemic have occurred in healthcare workers. Some have attributed this to inadequate provision of personal protective equipment (PPE). ⋯ Despite recent revisions to these guidelines, concerns remain that they offer insufficient protection to frontline NHS healthcare workers. In this report, we evaluate whether these concerns are merited, through critical appraisal of the available evidence, review of international PPE guidance, and consideration of the ethical implications.
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The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for specific treatments. One potential treatment is chloroquine and its derivatives, including hydroxychloroquine, which have both antiviral and anti-inflammatory effects. ⋯ Although some encouraging outcomes have been reported, and these results have been received enthusiastically, we recommend careful and critical evaluation of current evidence only when all methods and data are available for peer review. Chloroquine is safe and cheap. However, further evidence from coordinated multicentre trials is required before it can be confidently said whether it is effective against the current pandemic.
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Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed to control this current pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir (RDV). RDV shows broad-spectrum antiviral activity against RNA viruses, and previous studies with RdRps from Ebola virus and Middle East respiratory syndrome coronavirus (MERS-CoV) have revealed that delayed chain termination is RDV's plausible mechanism of action. ⋯ In this regard, the triphosphate forms of 2'-C-methylated compounds, including sofosbuvir, approved for the management of hepatitis C virus infection, and the broad-acting antivirals favipiravir and ribavirin, exhibited significant deficits. Furthermore, we provide evidence for the target specificity of RDV, as RDV-TP was less efficiently incorporated by the distantly related Lassa virus RdRp, and termination of RNA synthesis was not observed. These results collectively provide a unifying, refined mechanism of RDV-mediated RNA synthesis inhibition in coronaviruses and define this nucleotide analogue as a direct-acting antiviral.
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While some risk factors have been identified, the reasons for the disparities in disease progression with COVID-19 are unclear, with some patients developing progressive and severe disease while in others the course is benign. Given this sense of randomness, and in the absence of a definitive treatment, medical professionals can feel helpless. It is useful to remember how much can be done to affect the trajectory of illness, even without a 'magic bullet'. With evidence emerging that late presentation is directly associated with increased mortality, we make the case for increased vigilance in the community and earlier intervention.