BACKGROUND:Screening for SARS-CoV-2 antibodies is under way in some key worker groups; how this adds to self-reported COVID-19 illness is unclear. In this study, we investigate the association between self-reported belief of COVID-19 illness and seropositivity. METHODS:Cross-sectional study of three key worker streams comprising (A) Police and Fire & Rescue (2 sites) (B) healthcare workers (1 site) and (C) healthcare workers with previously positive PCR result (5 sites). We collected self-reported signs and symptoms of COVID-19 and compared this with serology results from two SARS-CoV-2 immunoassays (Roche Elecsys® and EUROIMMUN). RESULTS:Between 01 and 26 June, we recruited 2847 individuals (Stream A: 1,247, Stream B: 1,546 and Stream C: 154). Amongst those without previous positive PCR tests, 687/2,579 (26%) reported belief they had COVID-19, having experienced compatible symptoms; however, only 208 (30.3%) of these were seropositive on both immunoassays. Both immunoassays had high sensitivities relative to previous PCR positivity (>93%); there was also limited decline in antibody titres up to 110 days post symptom onset. Symptomatic but seronegative individuals had differing symptom profiles and shorter illnesses than seropositive individuals. CONCLUSION:Non-COVID-19 respiratory illness may have been mistaken for COVID-19 during the outbreak; laboratory testing is more specific than self-reported key worker beliefs in ascertaining past COVID-19 disease.

AbstractImmune correlates of protection from COVID-19 are incompletely understood. 2,826 keyworkers had T-SPOT®DiscoverySARS-CoV-2 tests (measuring interferon-γ secreting, SARS-CoV-2 responsive T cells, Oxford Immunotec Ltd), and anti-Spike S1 domain IgG antibody levels (EuroImmun AG) performed on recruitment into a cohort study. 285/2,826 (10.1%) of participants had positive SARS-CoV-2 RT-PCR tests, predominantly associated with symptomatic illness, during 200 days followup. T cell responses to Spike, Nucleoprotein and Matrix proteins (SNM responses) were detected in some participants at recruitment, as were anti-Spike S1 IgG antibodies; higher levels of both were associated with protection from subsequent SARS-CoV-2 test positivity. In volunteers with moderate antibody responses, who represented 39% (252/654) of those with detectable anti-Spike IgG, protection was partial, and higher with higher circulating T cell SNM responses. SARS-CoV-2 responsive T cell numbers predict protection in individuals with low anti-Spike IgG responses; serology alone underestimates the proportion of the population protected after infection.

BackgroundChile has one of the highest incidences of COVID-19 infection in the world. Primary care can play a key role in early detection and containment of the disease. There is a lack of information on the clinical profile of patients with suspected COVID-19 in primary care, and controversy on the effectiveness of rapid serologic tests in the diagnosis and surveillance of the disease.AimTo assess the effectiveness of rapid serologic testing in detection and surveillance of COVID-19 cases in primary care.Design & settingA longitudinal study was undertaken, which was based on a non-random sample of 522 participants, including 304 symptomatic patients and 218 high-risk asymptomatic individuals. They were receiving care at four primary health clinics in an underserved area in Santiago, Chile.MethodThe participants were systematically assessed and tested for COVID-19 with reverse transcriptase-polymerase chain reaction (RT-PCR) and serology at baseline, and were followed clinically and serologically for 3 weeks.ResultsThe prevalence rate of RT-PCR confirmed COVID-19 cases were 3.5 times higher in symptomatic patients (27.5%; 95% confidence interval [CI] = 22.1 to 32.8) compared with asymptomatic participants (7.9%; 95% CI = 4.3 to 11.6). Similarly, the immune response was significantly different between both groups. Sensitivity of serologic testing was 57.8% (95% CI = 44.8 to 70.1) during the third week of follow-up and specificity was 98.4% (95% CI = 95.5 to 99.7).ConclusionRapid serologic testing is ineffective for detecting asymptomatic or non-severe cases of COVID-19 at early stages of the disease, but can be of value for surveillance of immunity response in primary care. The clinical profile and immune response of patients with COVID-19 in primary care differs from those in hospital-based populations.

AbstractObjectiveTo measure the association between self-reported signs and symptoms and SARS-CoV-2 seropositivity.DesignCross-sectional study of three key worker groups.SettingSix acute NHS hospitals and two Police and Fire and Rescue sites in England.ParticipantsIndividuals were recruited from three streams: (A) Police and Fire and Rescue services (n = 1147), (B) healthcare workers (n = 1546) and (C) healthcare workers with previously positive virus detection (n = 154).Main outcome measuresDetection of anti-SARS-CoV-2 antibodies in plasma.Results943 of the 2847 participants (33%) reported belief they had had COVID-19, having experienced compatible symptoms (including 152 from Stream C). Among individuals reporting COVID-19 compatible symptoms, 466 (49%) were seronegative on both Nucleoprotein (Roche) and Spike-protein (EUROIMMUN) antibody assays. However, among the 268 individuals with prior positive SARS-CoV-2 tests, of whom 96% reported symptoms with onset a median of 63 days (IQR 52 – 75 days) prior to venesection, Roche and EUROIMMUN assays had 96.6% (95% CI 93.7% – 98.2%) and 93.3% (95% CI 89.6% – 95.7%) sensitivity respectively. Symptomatic but seronegative individuals had significantly earlier symptom onset dates than the symptomatic seropositive individuals, shorter illness duration and a much lower anosmia reporting frequency.ConclusionsSelf-reported belief of COVID-19 was common among our frontline worker cohort. About half of these individuals were seronegative, despite a high sensitivity of serology in this cohort, at least in individuals with previous positive PCR results. This is compatible with non-COVID-19 respiratory disease during the COVID-19 outbreak having been commonly mistaken for COVID-19 within the key worker cohort studied.What is already known on this topicScreening for SARS-CoV-2 antibodies is under way in some key worker groups; however, how this adds to self-reported COVID-19 illness is unclear. There are limited studies that investigate the association between self-reported belief of COVID-19 illness and seropositivity.What this study addsAbout one third of a large cohort of key frontline workers believed they had had COVID-19 infection. In around half of these there was no serological evidence of infection. Individuals who believed they had previous infection, but were seronegative, differed systematically from the seropositive individuals: disordered sense of taste and smell was less common, illness duration was shorter, and reported onset of illness commonly predated the main COVID-19 epidemic in the UK.Although some individuals with previous COVID-19 may be seronegative, among symptomatic individuals who had PCR-confirmed SARS-CoV-2 within our cohort, sensitivity of the two immunoassays used (Roche Elecsys ® and EUROIMMUN) exceeded 90%. Together, these data indicate that many key workers may falsely believe, based on symptomatic illness experienced during 2020, that they have had COVID-19. Further research investigating the relationship between antibody detection and protection from future infection, with and without a history of COVID-19 disease, will help define the role serological testing can play in clinical practice.

Objectives:To determine whether local trainer-led TARGET antibiotic interactive workshops improve antibiotic dispensing in general practice. Methods:Using a McNulty-Zelen-design randomized controlled trial within three regions of England, 152 general practices were stratified by clinical commissioning group, antibiotic dispensing rate and practice patient list size, then randomly allocated to intervention (offered TARGET workshop that incorporated a presentation, reflection on antibiotic data, promotion of patient and general practice (GP) staff resources, clinical scenarios and action planning, 73 practices) or control (usual practice, 79 practices). The primary outcome measure was total oral antibiotic items dispensed/1000 patients for the year after the workshop (or pseudo-workshop date for controls), adjusted for the previous year's dispensing. Results:Thirty-six (51%) intervention practices (166 GPs, 51 nurses and 101 other staff) accepted a TARGET workshop invitation. In the ITT analysis total antibiotic dispensing was 2.7% lower in intervention practices (95% CI -5.5% to 1%, P = 0.06) compared with controls. Dispensing in intervention practices was 4.4% lower for amoxicillin/ampicillin (95% CI 0.6%-8%, P = 0.02); 5.6% lower for trimethoprim (95% CI 0.7%-10.2%, P = 0.03); and a non-significant 7.1% higher for nitrofurantoin (95% CI -0.03 to 15%, P = 0.06). The Complier Average Causal Effect (CACE) analysis, which estimates impact in those that comply with assigned intervention, indicated 6.1% (95% CI 0.2%-11.7%, P = 0.04) lower total antibiotic dispensing in intervention practices and 11% (95% CI 1.6%-19.5%, P = 0.02) lower trimethoprim dispensing. Conclusions:This study within usual service provision found that TARGET antibiotic workshops can help improve antibiotic use, and therefore should be considered as part of any national antimicrobial stewardship initiatives. Additional local facilitation will be needed to encourage all general practices to participate.

Multi-locus sequence typing was used to reveal a high degree of diversity amongst the E. coli isolates with AmpC plasmid genes, and a high prevalence of the -32 mutation present.

The National Institute of Care Excellence (NICE) 2007 guidance CG54, on urinary tract infection (UTI) in children, states that clinicians should use urgent microscopy and culture as the preferred method for diagnosing UTI in the hospital setting for severe illness in children under 3 years old and from the GP setting in children under 3 years old with intermediate risk of severe illness. NICE also recommends that all 'infants and children with atypical UTI (including non-Escherichia coli infections) should have renal imaging after a first infection'. We surveyed all microbiology laboratories in England with Clinical Pathology Accreditation to determine standard operating procedures (SOPs) for urgent microscopy, culture and reporting of children's urine and to ascertain whether the SOPs facilitate compliance with NICE guidance. We undertook a computer search in six microbiology laboratories in south-west England to determine urine submissions and urine reports in children under 3 years. Seventy-three per cent of laboratories (110/150) participated. Enterobacteriaceae that were not E. coli were reported only as coliforms (rather than non-E. coli coliforms) by 61% (67/110) of laboratories. Eighty-eight per cent of laboratories (97/110) provided urgent microscopy for hospital and 54% for general practice (GP) paediatric urines; 61% of laboratories (confidence interval 52-70%) cultured 1 μl volume of urine, which equates to one colony if the bacterial load is 106 c.f.u. l(-1). Only 22% (24/110) of laboratories reported non-E. coli coliforms and provided urgent microscopy for both hospital and GP childhood urines; only three laboratories also cultured a 5 μl volume of urine. Only one of six laboratories in our submission audit had a significant increase in urine submissions and urines reported from children less than 3 years old between the predicted pre-2007 level in the absence of guidance and the 2008 level following publication of the NICE guidance. Less than a quarter of laboratories were providing a service that would allow clinicians to fully comply with the first line recommendations in the 2007 NICE UTI in children guidance. Laboratory urine submission report figures suggest that the guidance has not led to an increase in diagnosis of UTI in children under 3 years old.

Background The criteria used when GPs submit stool specimens for microbiological investigation are unknown. Aim To determine what criteria GPs use to send stool specimens, and if they are consistent with national guidance, and whether GPs would prescribe an antibiotic before they receive a result. Design and setting Questionnaire survey of 974 GPs in 172 surgeries in England. Method GPs were sent a questionnaire (23 questions) based on national guidance. Results Questionnaires were returned by 90% (154/172) of surgeries and 49% (477/968) of GPs. GPs reported sending stool specimens in about 50% of cases of suspected infectious diarrhoea, most commonly because of individual symptoms, rather than public health implications. Fewer considered sampling with antibiotic-associated diarrhoea post hospitalisation, or children with acute, painful, bloody diarrhoea; only 14% mentioned outbreaks as a reason. Nearly one-half of GPs reported they would consider antibiotics in suspected cases of Escherichia coli O157, which is contraindicated. Only 23% of GPs would send the recommended three specimens for ova, cysts, and parasites (OCP) examination. Although 89% of GPs gave some verbal advice on how to collect stool specimens, only 2% of GPs gave patients any written instructions. Conclusion GPs need more education to address gaps in knowledge about the risks and diagnosis of different infections in suspected infectious diarrhoea, especially Clostridium difficile post-antibiotics, E. coli O157, and requesting OCPs. Advice on reports, tick boxes, or links to guidance on electronic request forms may facilitate this.