Incidence, healthcare-seeking behaviours, antibiotic use and natural history of common infection syndromes in England: results from the Bug Watch community cohort study.

BACKGROUND: Better information on the typical course and management of acute common infections in the community could inform antibiotic stewardship campaigns. We aimed to investigate the incidence, management, and natural history of a range of infection syndromes (respiratory, gastrointestinal, mouth/dental, skin/soft tissue, urinary tract, and eye). METHODS: Bug Watch was an online prospective community cohort study of the general population in England (2018-2019) with weekly symptom reporting for 6 months. We combined symptom reports into infection syndromes, calculated incidence rates, described the proportion leading to healthcare-seeking behaviours and antibiotic use, and estimated duration and severity. RESULTS: The cohort comprised 873 individuals with 23,111 person-weeks follow-up. The mean age was 54 years and 528 (60%) were female. We identified 1422 infection syndromes, comprising 40,590 symptom reports. The incidence of respiratory tract infection syndromes was two per person year; for all other categories it was less than one. 194/1422 (14%) syndromes led to GP (or dentist) consultation and 136/1422 (10%) to antibiotic use. Symptoms usually resolved within a week and the third day was the most severe. CONCLUSIONS: Most people reported managing their symptoms without medical consultation. Interventions encouraging safe self-management across a range of acute infection syndromes could decrease pressure on primary healthcare services and support targets for reducing antibiotic prescribing.

Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data.

Background: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. Methods: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. Results: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. Conclusion: Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications.

Public activities preceding the onset of acute respiratory infection syndromes in adults in England - implications for the use of social distancing to control pandemic respiratory infections.

Background: Social distancing measures may reduce the spread of emerging respiratory infections however, there is little empirical data on how exposure to crowded places affects risk of acute respiratory infection. Methods: We used a case-crossover design nested in a community cohort to compare self-reported measures of activities during the week before infection onset and baseline periods. The design eliminates the effect of non-time-varying confounders. Time-varying confounders were addressed by exclusion of illnesses around the Christmas period and seasonal adjustment.  Results: 626 participants had paired data from the week before 1005 illnesses and the week before baseline. Each additional day of undertaking the following activities in the prior week was associated with illness onset: Spending more than five minutes in a room with someone (other than a household member) who has a cold (Seasonally adjusted OR 1·15, p=0·003); use of underground trains (1·31, p=0·036); use of supermarkets (1·32, p<0·001); attending a theatre, cinema or concert (1·26, p=0·032); eating out at a café, restaurant or canteen (1·25, p=0·003); and attending parties (1·47, p<0·001). Undertaking the following activities at least once in the previous week was associated with illness onset: using a bus, (aOR 1.48, p=0.049), shopping at small shops (1.9, p<0.002) attending a place of worship (1.81, p=0.005).    Conclusions: Exposure to potentially crowded places, public transport and to individuals with a cold increases risk of acquiring circulating acute respiratory infections. This suggests social distancing measures can have an important impact on slowing transmission of emerging respiratory infections.

Hand Hygiene Practices and the Risk of Human Coronavirus Infections in a UK Community Cohort.

Background: Hand hygiene may mitigate the spread of COVID-19 in community settings; however, empirical evidence is limited. Given reports of similar transmission mechanisms for COVID-19 and seasonal coronaviruses, we investigated whether hand hygiene impacted the risk of acquiring seasonal coronavirus infections. Methods: Data were drawn from three successive winter cohorts (2006-2009) of the England-wide Flu Watch study.  Participants ( n=1633) provided baseline estimates of hand hygiene behaviour. Coronavirus infections were identified from nasal swabs using RT-PCR. Poisson mixed models estimated the effect of hand hygiene on personal risk of coronavirus illness, both unadjusted and adjusted for confounding by age and healthcare worker status. Results: Moderate-frequency handwashing (6-10 times per day) predicted a lower personal risk of coronavirus infection (adjusted incidence rate ratio (aIRR) =0.64, p=0.04). There was no evidence for a dose-response effect of handwashing, with results for higher levels of hand hygiene (>10 times per day) not significant (aIRR =0.83, p=0.42). Conclusions: This is the first empirical evidence that regular handwashing can reduce personal risk of acquiring seasonal coronavirus infection. These findings support clear public health messaging around the protective effects of hand washing in the context of the current COVID-19 pandemic.

Seasonality and immunity to laboratory-confirmed seasonal coronaviruses (HCoV-NL63, HCoV-OC43, and HCoV-229E): results from the Flu Watch cohort study.

Background: There is currently a pandemic caused by the novel coronavirus SARS-CoV-2. The intensity and duration of this first and second waves in the UK may be dependent on whether SARS-CoV-2 transmits more effectively in the winter than the summer and the UK Government response is partially built upon the assumption that those infected will develop immunity to reinfection in the short term. In this paper we examine evidence for seasonality and immunity to laboratory-confirmed seasonal coronavirus (HCoV) from a prospective cohort study in England. Methods: In this analysis of the Flu Watch cohort, we examine seasonal trends for PCR-confirmed coronavirus infections (HCoV-NL63, HCoV-OC43, and HCoV-229E) in all participants during winter seasons (2006-2007, 2007-2008, 2008-2009) and during the first wave of the 2009 H1N1 influenza pandemic (May-Sep 2009). We also included data from the pandemic and 'post-pandemic' winter seasons (2009-2010 and 2010-2011) to identify individuals with two confirmed HCoV infections and examine evidence for immunity against homologous reinfection. Results: We tested 1,104 swabs taken during respiratory illness and detected HCoV in 199 during the first four seasons. The rate of confirmed HCoV infection across all seasons was 390 (95% CI 338-448) per 100,000 person-weeks; highest in the Nov-Mar 2008/9 season at 674 (95%CI 537-835) per 100,000 person-weeks. The highest rate was in February at 759 (95% CI 580-975) per 100,000 person-weeks. Data collected during May-Sep 2009 showed there was small amounts of ongoing transmission, with four cases detected during this period. Eight participants had two confirmed infections, of which none had the same strain twice. Conclusion: Our results provide evidence that HCoV infection in England is most intense in winter, but that there is a small amount of ongoing transmission during summer periods. We found some evidence of immunity against homologous reinfection.

Nosocomial transmission of influenza: A retrospective cross-sectional study using next generation sequencing at a hospital in England (2012-2014).

BACKGROUND: The extent of transmission of influenza in hospital settings is poorly understood. Next generation sequencing may improve this by providing information on the genetic relatedness of viral strains. OBJECTIVES: We aimed to apply next generation sequencing to describe transmission in hospital and compare with methods based on routinely-collected data. METHODS: All influenza samples taken through routine care from patients at University College London Hospitals NHS Foundation Trust (September 2012 to March 2014) were included. We conducted Illumina sequencing and identified genetic clusters. We compared nosocomial transmission estimates defined using classical methods (based on time from admission to sample) and genetic clustering. We identified pairs of cases with space-time links and assessed genetic relatedness. RESULTS: We sequenced influenza sampled from 214 patients. There were 180 unique genetic strains, 16 (8.8%) of which seeded a new transmission chain. Nosocomial transmission was indicated for 32 (15.0%) cases using the classical definition and 34 (15.8%) based on genetic clustering. Of the 50 patients in a genetic cluster, 11 (22.0%) had known space-time links with other cases in the same cluster. Genetic distances between pairs of cases with space-time links were lower than for pairs without spatial links (P < .001). CONCLUSIONS: Genetic data confirmed that nosocomial transmission contributes significantly to the hospital burden of influenza and elucidated transmission chains. Prospective next generation sequencing could support outbreak investigations and monitor the impact of infection and control measures.

Symptom reporting, healthcare-seeking behaviour and antibiotic use for common infections: protocol for Bug Watch, a prospective community cohort study.

INTRODUCTION: Antimicrobial resistance is a significant worldwide problem largely driven by selective pressure exerted through antibiotic use. Preserving antibiotics requires identification of opportunities to safely reduce prescriptions, for example in the management of mild common infections in the community. However, more information is needed on how infections are usually managed and what proportion lead to consultation and antibiotic use. The aim of this study is to quantify consultation and prescribing patterns in the community for a range of common acute infection syndromes (respiratory, gastrointestinal, skin/soft tissue, mouth/dental, eye and urinary tract). This will inform development of interventions to improve antibiotic stewardship as part of a larger programme of work, Preserving Antibiotics through Safe Stewardship. METHODS AND ANALYSIS: This will be an online prospective community cohort study in England. We will invite 19 510 adults who previously took part in a nationally representative survey (the Health Survey for England) and consented to be contacted about future studies. Adults will also be asked to register their children. Data collection will consist of a baseline registration survey followed by weekly surveys sent by email for 6 months. Weekly surveys will collect information on symptoms of common infections, healthcare-seeking behaviour and use of treatments including antibiotics. We will calculate the proportions of infection syndromes that lead to General Practitioner consultation and antibiotic prescription. We will investigate how healthcare-seeking and treatment behaviours vary by demographics, social deprivation, infection profiles and knowledge and attitudes towards antibiotics, and will apply behavioural theory to investigate barriers and enablers to these behaviours. ETHICS AND DISSEMINATION: This study has been given ethical approval by the University College London Research Ethics Committee (ID 11813/001). Each participant will provide informed consent upon registration. We will disseminate our work through publication in peer-reviewed academic journals. Anonymised data will be made available through the UK Data Service (https://www.ukdataservice.ac.uk/).

Effects of seasonal and pandemic influenza on health-related quality of life, work and school absence in England: Results from the Flu Watch cohort study.

BACKGROUND: Estimates of health-related quality of life (HRQoL) and work/school absences for influenza are typically based on medically attended cases or those meeting influenza-like-illness (ILI) case definitions and thus biased towards severe disease. Although community influenza cases are more common, estimates of their effects on HRQoL and absences are limited. OBJECTIVES: To measure quality-adjusted life days and years (QALDs and QALYs) lost and work/school absences among community cases of acute respiratory infections (ARI), ILI and influenza A and B and to estimate community burden of QALY loss and absences from influenza. PATIENTS/METHODS: Flu Watch was a community cohort in England from 2006 to 2011. Participants were followed up weekly. During respiratory illness, they prospectively recorded daily symptoms, work/school absences and EQ-5D-3L data and submitted nasal swabs for RT-PCR influenza testing. RESULTS: Average QALD lost was 0.26, 0.93, 1.61 and 1.84 for ARI, ILI, H1N1pdm09 and influenza B cases, respectively. 40% of influenza A cases and 24% of influenza B cases took time off work/school with an average duration of 3.6 and 2.4 days, respectively. In England, community influenza cases lost 24 300 QALYs in 2010/11 and had an estimated 2.9 million absences per season based on data from 2006/07 to 2009/10. CONCLUSIONS: Our QALDs and QALYs lost and work and school absence estimates are lower than previous estimates because we focus on community cases, most of which are mild, may not meet ILI definitions and do not result in healthcare consultations. Nevertheless, they contribute a substantial loss of HRQoL on a population level.

Investigating obesity as a risk factor for influenza-like illness during the 2009 H1N1 influenza pandemic using the Health Survey for England.

BACKGROUND: Following the 2009 H1N1 influenza pandemic, obesity was shown to be associated with severe influenza outcomes. It remains unclear whether obesity was a risk factor for milder influenza-like illness (ILI). OBJECTIVES: To determine whether obesity was associated with an increased risk of self-reported ILI during the 2009 H1N1 influenza pandemic using Health Survey for England (HSE) 2010 cross-sectional data. METHODS: This study used HSE data collected from English households between January and December 2010. Weight and height measurements were taken by trained fieldworkers to determine obesity. ILI was defined as a positive response to the question "Have you had a flu-like illness where you felt feverish and had a cough or sore throat?" with illness occurring between May and December 2009. Multivariable logistic regression was used to evaluate the association between obesity and ILI. RESULTS: The study comprised 8407 participants (6984 adults, 1436 children), among whom 24.7% (95% CI: 23.6-25.9) were classified as obese. Of obese participants, 12.8% (95% CI: 11.1-14.8) reported ILI compared to 11.8% (95% CI: 10.8-12.8) of non-obese participants. The adjusted OR for ILI associated with obesity was 1.16 (95% CI: 0.98-1.38, P=.093). For adults and children, the adjusted ORs were 1.16 (95% CI: 0.97-1.38, P=.101) and 1.26 (95% CI: 0.72-2.21, P=.422), respectively. CONCLUSION: Household survey data showed no evidence that obesity was associated with an increase in self-reported ILI during the 2009 H1N1 influenza pandemic in England. Further studies using active prospective ILI surveillance combined with laboratory reporting would reduce bias and improve accuracy of outcome measurements.

Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study.

RATIONALE: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. OBJECTIVES: To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. METHODS: We quantified influenza A(H3N2) virus-specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. MEASUREMENTS AND MAIN RESULTS: A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. CONCLUSIONS: Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.

Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study.

BACKGROUND: Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden. METHODS: Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006-11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable. FINDINGS: Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16-22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13-34), suggesting most influenza infections are asymptomatic. 25% (18-35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10-26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2. INTERPRETATION: Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2. FUNDING: Medical Research Council and the Wellcome Trust.