Accuracy of Rapid Point-of-Care Antibody Test in patients with suspected or confirmed COVID-19

ObjectivesTo assess the real-world diagnostic accuracy of the Livzon point-of-care rapid test for antibodies to SARS-COV-2 DesignProspective cohort study SettingDistrict general hospital in England Participants173 Patients and 224 hospital staff with a history of COVID-19 symptoms, and who underwent PCR and/or reference antibody testing for COVID-19. InterventionsThe Livzon point-of-care (POC) lateral flow immunoassay rapid antibody test (IgM and IgG) was conducted at least 7 days after onset of symptoms and compared to the composite reference standard of PCR for SARS-COV-2 plus reference laboratory testing for antibodies to SARS-COV-2. The SARS-CoV-2 RT-PCR was tested using the available molecular technology during the study time (PHE laboratories, GeneXpert(R) system Xpert, Xpress SARS-CoV-2 and Source bioscience laboratory). All molecular platforms/assays were PHE/NHSE approved. The reference antibody test was the Elecsys Anti-SARS-CoV-2 assay (Roche diagnostics GmBH). Main outcome measuresSensitivity and specificity of the rapid antibody test ResultsThe reference antibody test was positive in 190/268 (70.9%) of participants with a history of symptoms suggestive of COVID-19; in the majority (n=312) the POC test was taken 35 days or more after onset of symptoms. The POC antibody test had an overall sensitivity of 90.1% (292/328, 95% CI 86.3 - 93.1) and specificity of 100% (68/68, 95% CI 94.7 - 100) for confirming prior SARS-CoV-2 infection when compared to the composite reference standard. Sensitivity was 97.8% (89/92, 95% CI 92.3% to 99.7%) in participants who had been admitted to hospital and 84.4% (124/147, 95% CI 77.5% to 89.8%) in those with milder illness who had never been seen in hospital. ConclusionsThe Livzon point-of-care antibody test had comparable sensitivity and specificity to the reference laboratory antibody test, so could be used in clinical settings to support decision-making about patients presenting with more than 10 days of symptoms of COVID-19. What is already known on this topic- Presence of IgG and IgM antibodies to SARS-COV-2 indicates that the person was infected at least 7 days previously and is usually no longer infectious. - Rapid point-of-care tests for antibodies to SARS-COV-2 are widely available, cheap and easy to use - Preliminary evaluations suggested that rapid antibody tests may have insufficient accuracy to be useful for testing individual patients. What this study adds- The rapid point-of-care test for antibodies to SARS-COV-2 was 90.1% sensitive and 100% specific compared to reference standards for prior infection with COVID-19. - This is comparable to reference antibody tests - The point-of-care test evaluated in this study could be used to support clinical decision-making in real time, for patients presenting with symptoms of possible COVID-19 with at least 10 days of symptoms.

Effectiveness of digital interventions to improve household and community infection prevention and control behaviours and to reduce incidence of respiratory and/or gastro-intestinal infections: A rapid systematic review

BackgroundDigital interventions have potential to efficiently support improved hygiene practices to reduce transmission of COVID-19. ObjectiveTo evaluate the evidence for digital interventions to improve hygiene practices within the community. MethodsWe reviewed articles published between 01 January 2000 and 26 May 2019 that presented a controlled trial of a digital intervention to improve hygiene behaviours in the community. We searched MEDLINE, Embase, PsycINFO, Cochrane Controlled Register of Trials (CENTRAL), China National Knowledge Infrastructure and grey literature. Trials in hospitals were excluded, as were trials aiming at prevention of sexually transmitted infections; only target diseases with transmission mechanisms similar to COVID-19 (e.g. respiratory and gastrointestinal infections) were included. Trials had to evaluate a uniquely digital component of an intervention. Study designs were limited to randomised controlled trials, controlled before-and-after trials, and interrupted time series analyses. Outcomes could be either incidence of infections or change in hygiene behaviours. The Risk of Bias 2 tool was used to assess study quality. ResultsWe found seven studies that met the inclusion criteria. Six studies reported successfully improving self-reported hygiene behaviour or health outcomes, but only one of these six trials confirmed improvements using objective measures (reduced consultations and antibiotic prescriptions), Germ Defence. Settings included kindergartens, workplaces, and service station restrooms. Modes of delivery were diverse: WeChat, website, text messages, audio messages to mobiles, electronic billboards, and electronic personal care records. Four interventions targeted parents of young children with educational materials. Two targeted the general population; these also used behaviour change techniques or theory to inform the intervention. Only one trial had low risk of bias, Germ Defence; the most common concerns were lack of information about the randomisation, possible bias in reporting of behavioural outcomes, and lack of an analysis plan and possible selective reporting of results. ConclusionThere was only one intervention that was judged to be at low risk of bias, Germ Defence, which reduced incidence and severity of illness, as confirmed by objective measures. Further evaluation is required to determine the effectiveness of the other interventions reviewed.

Current infection control behaviour patterns in the UK, and how they can be improved by 'Germ Defence', an online behavioural intervention to reduce the spread of COVID-19 in the home.

BackgroundGerm Defence (https://germdefence.org/) is a freely available website providing behavioural advice for infection control within households, using behaviour change techniques. This observational study reports current infection control behaviours in the home in UK and international users of the website, and examine how they might be improved to reduce the spread of COVID-19. Method28,285 users sought advice from four website pathways (to protect themselves generally, to protect others if the user was showing symptoms, to protect themselves if household members were showing symptoms, and to protect a household member who is at high risk) and completed outcome measures of current infection control behaviours within the home (self-isolation, social distancing, putting shopping/packages aside, wearing face-covering, cleaning and disinfecting, handwashing), and intentions to change these behaviours. ResultsCurrent user behaviours mean scores varied across all infection control measures but were between sometimes and quite often, except handwashing ( very often). Behaviours were similar regardless of the website pathway used. After using Germ Defence, users recorded intentions to improve infection control behaviour across all website pathways and for all behaviours. ConclusionsSelf-reported infection control behaviours other than handwashing are lower than is optimal for infection prevention, although reported handwashing is much higher. The advice using behaviour change techniques in Germ Defence led to intentions to improve these behaviours. This has been shown previously to reduce the incidence, severity and transmission of infections. These findings suggest that promoting Germ Defence within national and local public health guidance could reduce COVID-19 transmission. O_TEXTBOXSection 1: What is already known on this topicO_LIUntil a vaccine can prevent COVID-19, protective behaviours (such as social distancing, handwashing, cleaning/disinfecting) must be used to limit the spread. C_LIO_LIA digital behaviour change intervention to improve protective behaviours (handwashing) within the home succeeded in reducing infection transmission, healthcare utilisation and infection severity during the H1N1 pandemic (the PRIMIT trial). C_LIO_LIWe need to understand current levels of protective behaviour in the UK, and how to improve them, to prevent a second wave. C_LI Section 2: What this study addsO_LIOur study suggests that few people are undertaking sufficient protective infection control behaviours in the home to reduce transmission C_LIO_LIProviding targeted digital interventions such as Germ Defence (for example through public health and primary care networks) offers a feasible method of increasing intentions to undertake these behaviours. C_LI C_TEXTBOX

Currently prescribed drugs in the UK that could up or downregulate ACE2 in COVID-19 disease: A systematic review

ObjectiveTo review evidence on routinely prescribed drugs in the UK that could up or downregulate Angiotensin Converting Enzyme 2 (ACE2) and potentially affect COVID-19 disease DesignSystematic review Data sourceMEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science Study selectionAny design with animal or human models examining a currently prescribed UK drug compared to a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. Data extraction and synthesisMEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1st April 2020. Methodological quality was assessed using the SYRCLEs risk of bias tool for animal studies and Cochrane risk of bias tool for human studies. ResultsWe screened 3,360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and 102 were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were Angiotensin Receptor Blockers (ARBs) (n= 55) and Angiotensin-Converting Enzyme-Inhibitors (ACE-I) (n= 22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel-blockers (n=3) GLP-1 agonists (n=2) and NSAIDs (n=2). ConclusionsThere is an abundance of academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty amongst patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in-vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease. O_LSTStrengths and limitationsC_LSTO_LIThis review addresses a high priority patient and clinician concern C_LIO_LIGiven the limited evidence on the subject, we included human and animal models both in vivo and in vitro for a comprehensive review C_LIO_LIThis is the first systematic review specifically focussed on UK prescribed drugs that could alter ACE2 in COVID-19 disease C_LIO_LIThe heterogeneity across study designs and models meant meta-analysis was not suitable C_LIO_LIGiven the rapidly changing evidence as the pandemic progresses, it is possible that new studies have since been published. C_LI

Drug treatments affecting ACE2 in COVID-19 infection: a systematic review protocol

BackgroundThe SARS-CoV-2 virus causing COVID-19 binds human angiotensin-converting enzyme 2 (ACE2) receptors in human tissues. ACE2 expression may be associated with COVID-19 infection and mortality rates. Routinely prescribed drugs which up- or down-regulate ACE2 expression are therefore of critical research interest as agents which might promote or reduce risk of COVID-19 infection in a susceptible population. AimTo review evidence on routinely prescribed drug treatments in the UK that could up- or down-regulate ACE2 and potentially affect COVID-19 infection. Design and settingSystematic review of studies published in MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science from inception to April 1st 2020. MethodA systematic review will be conducted in line with PRISMA guidelines. Inclusion criteria will be: i) assess effect of drug exposure on ACE2 level; ii) drug is included in British National Formulary (BNF) and therefore available to prescribe in UK; iii) a control, placebo or sham group is included as comparator. Exclusion criteria will be: i) ACE2 measurement in utero; ii) ACE2 measurement in children under 18 years; iii) drug not in BNF; iv) review article. Quality will be assessed using the Cochrane risk of bias tool for human studies, and the SYRCLE risk of bias tool for animal studies. ResultsData will be reported in summary tables and narrative synthesis. ConclusionThis systematic review will identify drug therapies which may increase or decrease ACE2 expression. This might identify medications increasing risk of COVID-19 transmission, or as targets for intervention in mitigating transmission.