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BackgroundPeople with Long Covid (Post-Acute Sequelae of Covid-19) describe multiple symptoms which vary between and within individuals over relatively short time intervals. We aimed to describe the real-time associations between different symptoms and between symptoms and physical activity at the individual patient level. Methods and FindingsIntensive longitudinal study of 82 adults with self-reported Long Covid (median duration 12-18 months). Data collection involved a smartphone app with 5 daily entries over 14 days and continuous wearing of a wrist accelerometer. Data items included 7 symptoms (Visual Analog Scales) and perceived demands in the preceding period (Likert scales). Activity was measured using mean acceleration in the 3-hour periods preceding and following app data entry. Analysis used within-person correlations of symptoms pairs and both pooled and individual symptom networks derived from graphical vector autoregression. App data was suitable for analysis from 74 participants (90%) comprising 4022 entries representing 77.6% of possible entries. Symptoms varied substantially within individuals and were only weakly auto-correlated. The strongest between-subject symptom correlations were of fatigue with pain (partial coefficient 0.5) and cognitive difficulty with light-headedness (0.41). Pooled within-subject correlations showed fatigue correlated with cognitive difficulty (partial coefficient 0.2) pain (0.19) breathlessness (0.15) and light-headedness (0.12) but not anxiety. Cognitive difficulty was correlated with anxiety and light-headedness (partial coefficients 0.16 and 0.17). Individual participant correlation heatmaps and symptom networks showed no clear patterns indicative of distinct phenotypes. Symptoms, including fatigue, were inconsistently correlated with prior or subsequent physical activity: this may reflect adjustment of activity in response to symptoms. Delayed worsening of symptoms after the highest activity peak was observed in 7 participants. ConclusionSymptoms of Long Covid vary within individuals over short time scales, with heterogenous patterns of symptom correlation. The findings are compatible with altered central symptom processing as an additional factor in Long Covid.
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The effect of heat on SARS-CoV-2/England/2/2020 viability was assessed by plaque assay and virus culture. Heating to 56{degrees}C and 60{degrees}C for 15, 30 and 60 minutes led to a reduction in titre of between 2.1 and 4.9 log10 pfu/ml but complete inactivation was not observed. At 80{degrees}C plaques were observed after 15 and 30 minutes of heating, however after 60 minutes viable virus was only detected following virus culture. Heating to 80{degrees}C for 90 minutes and 95{degrees}C for 1 and 5 minutes resulted in no viable virus being detected. At 56{degrees}C and 60{degrees}C significant variability between replicates was observed and the titre often increased with heat-treatment time. Nucleic acids were extracted and tested by RT-PCR. Sensitivity of the RT-PCR was not compromised by heating to 56{degrees}C and 60{degrees}C. Heating to 80{degrees}C for 30 minutes or more and 95{degrees}C for 1 or 5 minutes however, resulted in an increase of at least three Ct values. This increase remained constant when different dilutions of virus underwent heat treatment. This indicates that high temperature heat inactivation of clinical samples prior to nucleic acid extraction could significantly affect the ability to detect virus in clinical samples from patients with lower viral loads by RT-PCR.
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The COVID-19 pandemic has necessitated a rapid multi-faceted response by the scientific community, bringing researchers, health officials and industry together to address the ongoing public health emergency. To meet this challenge, participants need an informed approach for working safely with the etiological agent, the novel human coronavirus SARS-CoV-2. Work with infectious SARS-CoV-2 is currently restricted to high-containment laboratories, but material can be handled at a lower containment level after inactivation. Given the wide array of inactivation reagents that are being used in laboratories during this pandemic, it is vital that their effectiveness is thoroughly investigated. Here, we evaluated a total of 23 commercial reagents designed for clinical sample transportation, nucleic acid extraction and virus inactivation for their ability to inactivate SARS-CoV-2, as well as seven other common chemicals including detergents and fixatives. As part of this study, we have also tested five filtration matrices for their effectiveness at removing the cytotoxic elements of each reagent, permitting accurate determination of levels of infectious virus remaining following treatment. In addition to providing critical data informing inactivation methods and risk assessments for diagnostic and research laboratories working with SARS-CoV-2, these data provide a framework for other laboratories to validate their inactivation processes and to guide similar studies for other pathogens.
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BackgroundThe COVID-19 pandemic has led to unprecedented demand for personal protective equipment. Shortages of surgical masks and filtering facepiece respirators has led to the extended use or re-use of single-use respirators and surgical masks by frontline healthcare workers. The evidence base underpinning such practices has been questioned. ObjectivesTo summarise guidance and synthesise systematic review evidence on extended use, re-use or reprocessing of single-use surgical masks or filtering facepiece respirators. MethodsA targeted search of the World Health Organization, European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and Public Health England websites was conducted to identify guidance. Four databases (Medline, Pubmed, Epistemonikos, Cochrane Database of Systematic Reviews) and three preprint repositories (Litcovid, MedRxiv and Open Science Framework) were searched for relevant systematic reviews. Record screening and data extraction was conducted by two reviewers. Quality of included systematic reviews was appraised using the AMSTAR-2 checklist. Findings were integrated and narratively synthesised to highlight the extent to which key claims in guidance documents were supported by research evidence. ResultsSix guidance documents were identified. All note that extended use or re-use of single-use surgical masks and respirators (with or without reprocessing) should be considered only in situations of critical shortage. Extended use was generally favoured over re-use because of reduced risk of contact transmission. Four high-quality systematic reviews were included: three focused on reprocessing (decontamination) of N95 respirators and one focused on reprocessing of surgical masks. There was limited evidence on the impact of extended use on masks and respirators. Vaporised hydrogen peroxide and ultraviolet germicidal irradiation were highlighted as the most promising reprocessing methods, but evidence on the relative efficacy and safety of different methods was limited. We found no well-established methods for reprocessing respirators at scale. ConclusionsThere is limited evidence on the impact of extended use and re-use of surgical masks and respirators. Where extended use or re-use is being practiced, healthcare organisations should ensure that policies and systems are in place to ensure these practices are carried out safely and in line with available guidance.
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ObjectivesIn the context of the Covid-19 pandemic, to identify the range of filtering respirators that can be used in patient care and synthesise evidence to guide the selection and use of different respirator types. DesignComparative analysis of international standards for filtering respirators and rapid review of their performance and impact in healthcare. Data sourcesWebsites of international standards organisations, Medline and EMBASE (final search 11th May 2020), with hand-searching of references and citations. Study selectionGuided by the SPIDER tool, we included studies whose sample was healthcare workers (including students). The phenomenon of interest was respirators, including disposable and reusable types. Study designs including cross-sectional, observational cohort, simulation, interview and focus group. Evaluation approaches included test of respirator performance, test of clinician performance or adherence, self-reported comfort and impact, and perceptions of use. Research types included quantitative, qualitative and mixed methods. We excluded studies comparing the effectiveness of respirators with other forms of protective equipment. Data extraction, analysis and synthesisTwo reviewers extracted data using a template. Suitability for inclusion in the analysis was judged by two reviewers. We synthesised standards by tabulating data according to key criteria. For the empirical studies, we coded data thematically followed by narrative synthesis. ResultsWe included relevant standards from 8 authorities across Europe, North and South America, Asia and Australasia. 39 research studies met our inclusion criteria. There were no instances of comparable publications suitable for quantitative comparison. There were four main findings. First, international standards for respirators apply across workplace settings and are broadly comparable across jurisdictions. Second, effective and safe respirator use depends on proper fitting and fit-testing. Third, all respirator types carry a burden to the user of discomfort and interference with communication which may limit their safe use over long periods; studies suggest that they have little impact on specific clinical skills in the short term but there is limited evidence on the impact of prolonged wearing. Finally, some clinical activities, particularly chest compressions, reduce the performance of filtering facepiece respirators. ConclusionA wide range of respirator types and models is available for use in patient care during respiratory pandemics. Careful consideration of performance and impact of respirators is needed to maximise protection of healthcare workers and minimise disruption to the delivery of care.