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BackgroundContinuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered aerosol-generating procedures (AGPs) in the treatment of COVID-19. We aimed to measure air and surface environmental contamination of SARS-CoV-2 virus when CPAP and HFNO were used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients. Methods30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen [≥]0.4 to maintain oxygen saturations [≥]94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. RT qPCR analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus. ResultsOverall 21/30 (70%) of participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination. Only one nasopharyngeal sample was culture positive. ConclusionsThe use of CPAP and HFNO to treat moderate/severe COVID-19 was not associated with significantly higher levels of air or surface viral contamination in the immediate care environment.
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BackgroundWe conducted a systematic review and individual patient data (IPD) meta-analysis to evaluate the diagnostic accuracy of a commercial point-of-care test, the FebriDx lateral flow device (LFD), in adult patients with suspected COVID-19. The FebriDx LFD is designed to distinguish between viral and bacterial respiratory infection. MethodsWe searched MEDLINE, EMBASE, PubMed, Google Scholar, LitCovid, ClinicalTrials.gov and preprint servers on the 13th of January 2021 to identify studies reporting diagnostic accuracy of FebriDx (myxovirus resistance protein A component) versus real time reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 in adult patients suspected of COVID-19. IPD were sought from studies meeting the eligibility criteria. Studies were screened for risk of bias using the QUADAS-2 tool. A bivariate linear mixed model was fitted to the data to obtain a pooled estimate of sensitivity and specificity with 95% confidence intervals (95% CIs). A summary receiver operating characteristic (SROC) curve of the model was constructed. A sub-group analysis was performed by meta-regression using the same modelling approach to compare pooled estimates of sensitivity and specificity between patients with a symptom duration of 0 to 7 days and >7 days, and patients aged between 16 to 73 years and >73 years. ResultsTen studies were screened, and three studies with a total of 1481 patients receiving hospital care were included. FebriDx produced an estimated pooled sensitivity of 0.911 (95% CI: 0.855-0.946) and specificity of 0.868 (95% CI: 0.802-0.915) compared to RT-PCR. There were no significant differences between the sub-groups of 0 to 7 days and >7 days in estimated pooled sensitivity (p = 0.473) or specificity (p = 0.853). There were also no significant differences between the sub-groups of 16 to 73 years of age and >73 years of age in estimated pooled sensitivity (p = 0.946) or specificity (p = 0.486). ConclusionsBased on the results of three studies, the FebriDx LFD had high diagnostic accuracy for COVID-19 in a hospital setting, however, the pooled estimates of sensitivity and specificity should be interpreted with caution due to the small number of studies included, risk of bias, and inconsistent reference standards. Further research is required to confirm these findings, and determine how FebriDx would perform in different healthcare settings and patient populations. Trial registrationThis study was conducted at pace as part of the COVID-19 National Diagnostic Research and Evaluation Platform (CONDOR) national test evaluation programme (https://www.condor-platform.org), and as a result, no protocol was developed, and the study was not registered. Lay summaryTests to diagnose COVID-19 are crucial to help control the spread of the disease and to guide treatment. Over the last few months, tests have been developed to diagnose COVID-19 either by detecting the presence of the virus or by detecting specific markers linked to the virus being active in the body. These tests use complex machines in laboratories accepting samples from large geographical areas. Sometimes it takes days for test results to come back. So, to reduce the wait for results, new portable tests are being developed. These point-of-care (POC) tests are designed to work close to where patients require assessment and care such as hospital emergency departments, GP surgeries or care homes. For these new POC tests to be useful, they should ideally be as good as standard laboratory tests. In this study we looked at published research into a new test called FebriDx. FebriDx is a POC test that detects the bodys response to infection, and is claimed to be able to detect the presence of any viral infection, including infections due to the SARS-CoV-2 virus which causes COVID-19, as well as bacterial infections which can have similar symptoms. The FebriDx result was compared with standard laboratory tests for COVID-19 performed on the same patients throat and nose swab sample. We were able to analyse data from three studies with a total of 1481 adult patients who were receiving hospital care with symptoms of COVID-19 during the UK pandemic. Approximately one fifth of the patients were diagnosed as positive for SARS-CoV-2 virus using standard laboratory tests for COVID-19. Our analysis demonstrated that FebriDx correctly identified 91 out of 100 patients who had COVID-19 according to the standard laboratory test. FebriDx also correctly identified 87 out of 100 patients who did not have COVID-19 according to the standard laboratory test. These results have important implications for how these tests could be used. As there were slightly fewer FebriDx false results when the results of the standard laboratory test were positive (9 out of 100) than when the results of the standard laboratory test were negative (13 out of 100), we can have slightly more confidence in a positive test result using FebriDx than a negative FebriDx result. Overall, we have shown that the FebriDx POC test performed well during the UK COVID-19 pandemic when compared with laboratory tests, especially when COVID-19 was indicated. For the future, this means that the FebriDx POC test might be helpful in making a quick clinical decision on whether to isolate a patient with COVID-19-like symptoms arriving in a busy emergency department. However, our results indicate it would not completely replace the need to conduct a laboratory test in certain cases to confirm COVID-19. There are limitations to our findings. For example, we do not know if FebriDx will work in a similar way with patients in different settings such as in the community or care homes. Similarly, we do not know whether other viral and bacterial infections which cause similar COVID-19 symptoms, and are more common in the autumn and winter months, could influence the FebriDx test accuracy. Our findings are also only based on three studies.
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BackgroundEarly clinical reports have suggested that the prevalence of thrombotic complications in the pathogenesis of COVID-19 may be as high as 30% in intensive care unit (ICU)-admitted patients and could be a major factor contributing to mortality. However, mechanisms underlying COVID-19-associated thrombo-coagulopathy, and its impact on patient morbidity and mortality, are still poorly understood. MethodsWe performed a comprehensive analysis of coagulation and thromboinflammatory factors in plasma from COVID-19 patients with varying degrees of disease severity. Furthermore, we assessed the functional impact of these factors on clot formation and clot lysis. ResultsAcross all COVID-19 disease severities (mild, moderate and severe) we observed a significant increase (6-fold) in the concentration of ultra-large von Willebrand factor (UL-VWF) multimers compared to healthy controls. This is likely the result of an interleukin (IL)-6 driven imbalance of VWF and the regulatory protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Upregulation of this key pro-coagulant pathway may also be influenced by the observed increase (~6-fold) in plasma -defensins, a consequence of increased numbers of neutrophils and neutrophil activation. Markers of endothelial, platelet and leukocyte activation were accompanied by increased plasma concentrations of Factor XIII (FXIII) and plasminogen activator inhibitor (PAI)-1. In patients with high FXIII we observed alteration of the fibrin network structure in in vitro assays of clot formation, which coupled with increased PAI-1, prolonged the time to clot lysis by the t-PA/plasmin fibrinolytic pathway by 52% across all COVID-19 patients (n=23). ConclusionsWe show that an imbalance in the VWF/ADAMTS13 axis causing increased VWF reactivity may contribute to the formation of platelet-rich thrombi in the pulmonary vasculature of COVID-19 patients. Through immune and inflammatory responses, COVID-19 also alters the balance of factors involved in fibrin generation and fibrinolysis which accounts for the persistent fibrin deposition previously observed in post-mortem lung tissue. What is new?O_LIIn all COVID-19 patients, even mild cases, UL-VWF is present in plasma due to the alteration of VWF and ADAMTS13 concentrations, likely driven by increased IL-6 and -defensins. C_LIO_LIIncreased plasma FXIII alters fibrin structure and enhances incorporation of VWF into fibrin clusters. C_LIO_LIDefective fibrin structure, coupled with increased plasma PAI-1 and 2-antiplasmin, inhibits fibrinolysis by t-PA/plasmin. C_LI What are the clinical implications?O_LIProphylactic anticoagulation and management of thrombotic complications in COVID-19 patients are ongoing challenges requiring a better understanding of the coagulopathic mechanisms involved. C_LIO_LIWe have identified FXIII and VWF as potential therapeutic targets for treating fibrin formation defects in COVID-19 patients. C_LIO_LIWe have identified a multifaceted fibrinolytic resistance in COVID-19 patient plasma with potential implications in the treatment of secondary thrombotic events such as acute ischaemic stroke or massive pulmonary embolism. C_LI
