Tracking COVID-19 in England and Wales: Insights from Virus Watch - a prospective community cohort study (preprint)

BackgroundVirus Watch is a prospective community cohort study of COVID-19 of 28{square},527 households in England and Wales designed to estimate the incidence of PCR-confirmed COVID-19 in those with respiratory presentations and examine symptom profiles and transmission of COVID-19 in relation to population movement and behaviour. The Office for National Statistics (ONS) COVID-19 infection survey (CIS) was the largest regular survey of COVID-19 infections and antibodies in the UK and included 227,797 households. In this analysis, we aimed to compare incidence rate estimates from the two studies to understand differences in estimates from the two study designs. MethodsWe used the Virus Watch prospective community cohort study to estimate the overall SARS-CoV-2 incidence rate and incidence rate by age in England and Wales from June 2020 to February 2023. Virus Watch data consisted of self-reported laboratory COVID-19 test results and linkage to the Second Generation Surveillance System, the UK national database for COVID-19 testing. We compared our findings with modelled incidence rates from ONS CIS using 3-day rolling Pearsons correlation to measure synchrony. Results58,628 participants were recruited into the Virus Watch study between June 2020 and March 2022, of whom 52,526 (90%) were reported to be living in England and 1,532 (2.6%) in Wales. COVID-19 incidence rates were initially similar across age groups until the Delta wave when rates increased at different magnitudes. During the Omicron BA.1, the 0-14 age group had the highest incidence rates, which shifted to the 25-44 age group with Omicron BA.2, 4, and 5 dominance. We found strong synchrony between Virus Watch and ONS CIS COVID-19 incidence estimates for England and Wales, both with and without the incorporation of linked national testing data into the Virus Watch study. In particular, the magnitude and trend of Virus Watch- and ONS-estimated rates for England were generally consistent, although Virus Watch-estimated peaks of infection during the Omicron BA.1 and 2 waves were found to be lower than estimates from the ONS. ConclusionOur findings suggest that the Virus Watch research approach is a low-cost and effective method for on-going surveillance of COVID-19 regardless of the availability of national testing in the UK. Similar approaches can also be utilised by low-resource settings to provide accurate incidence rate estimates to better monitor and respond to COVID-19 as well as other acute respiratory diseases in the future.

The incidence of COVID-19-related hospitalisation in migrants in the UK: Findings from the Virus Watch prospective community cohort study (preprint)

Background: Migrants in the UK may be at higher risk of SARS-CoV-2 exposure; however, little is known about their risk of COVID-19-related hospitalisation during waves 1-3 of the pandemic. Methods: We analysed secondary care data linked to Virus Watch study data for adults and estimated COVID-19-related hospitalisation incidence rates by migration status. To estimate the total effect of migration status on COVID-19 hospitalisation rates, we ran fixed-effect Poisson regression for wave 1 (01/03/2020-31/08/2020; wildtype), and fixed-effect negative binomial regressions for waves 2 (01/09/2020-31/05/2021; Alpha) and 3 (01/06/2020-31/11/2021; Delta). Results of all models were then meta-analysed. Results: Of 30,276 adults in the analyses, 26,492 (87.5%) were UK-born and 3,784 (12.5%) were migrants. COVID-19-related hospitalisation incidence rates for UK-born and migrant individuals across waves 1-3 were 2.7 [95% CI 2.2-3.2], and 4.6 [3.1-6.7] per 1,000 person-years, respectively. Pooled incidence rate ratios across waves suggested increased rate of COVID-19-related hospitalisation in migrants compared to UK-born individuals in unadjusted 1.68 [1.08-2.60] and adjusted analyses 1.35 [0.71-2.60]. Conclusions: Our findings suggest migration populations in the UK have excess risk of COVID-19-related hospitalisations and underscore the need for more equitable interventions particularly aimed at COVID-19 vaccination uptake among migrants.

Glasses and risk of COVID-19 transmission - analysis of the Virus Watch Community Cohort study. (preprint)

Background Respiratory viruses, including SARS-CoV-2, can infect the eyes or pass into the nose via the nasolacrimal duct. The importance of transmission via the eyes is unknown but might plausibly be reduced in those who wear glasses. Previous studies have mainly focussed on protective eyewear in healthcare settings. Methods Participants from the Virus Watch prospective community cohort study in England and Wales responded to a questionnaire on the use of glasses and contact lenses. This included frequency of use, purpose, and likelihood of wearing a mask with glasses. Infection was confirmed through data linkage with Second Generation Surveillance System (Pillar 1 and Pillar 2), weekly questionnaires to self-report positive polymerase chain reaction or lateral flow results, and, for a subgroup, monthly capillary blood testing for antibodies (nucleocapsid and spike). A multivariable logistic regression model, controlling for age, sex, income and occupation, was used to identify odds of infection depending on the frequency and purpose of using glasses or contact lenses. Findings 19,166 Virus Watch participants responded to the questionnaire, with 13,681 (71.3%, CI 70.7-72.0) reporting they wore glasses. A multivariable logistic regression model showed a 15% lower odds of infection for those who reported using glasses always for general use (OR 0.85, 95% 0.77-0.95, p = 0.002) compared to those who never wore glasses. The protective effect was reduced in those who said that wearing glasses interfered with mask wearing. No protective effect was seen for contact lens wearers. Interpretation People who wear glasses have a moderate reduction in risk of COVID-19 infection highlighting the importance of the eye as a route of infection. Eye protection may make a valuable contribution to the reduction of transmission in community and healthcare settings.

Nucleocapsid and spike antibody responses post virologically confirmed SARS-CoV-2 infection: An observational analysis in the Virus Watch community cohort (preprint)

Introduction: Seroprevalence studies can provide a measure of cumulative incidence of SARS-CoV-2 infection, but a better understanding of antibody dynamics following infection is needed to assess longevity of detectability. Infection is characterised by detection of spike (anti-S) and nucleocapsid (anti-N) antibodies, whereas vaccination only stimulates anti-S. Consequently, in the context of a highly vaccinated population, presence of anti-N can be used as a marker of previous infection but waning over time may limit its use. Methods: Adults aged 18 years and older, from households enrolled in the Virus Watch prospective community cohort study in England and Wales, provided monthly capillary blood samples which were tested for anti-S and anti-N. Participants self-reported vaccination dates and past medical history. Prior polymerase chain reaction (PCR) swabs were obtained through Second Generation Surveillance System (SGSS) linkage data. Primary outcome variables were seropositivity (antibodies at or above the manufacturer's cut-off for positivity) and total anti-N and anti-S levels after PCR confirmed infection. Outcomes were analysed by days since infection, self-reported demographic and clinical factors. Results: A total of 13,802 eligible individuals, median age 63, provided 58,770 capillary blood samples. 537 of these had a prior positive PCR confirmed SARS-CoV-2 infection 0-269 days before the antibody sample date. 432 out of the 537 (80.44%) were anti-N positive and detection remained stable through-out follow-up. Median anti-N levels peaked between days 90 and 119 post PCR results and then began to decline. Logistic regression models, both univariable and multivariable, only showed higher odds of positive anti-N result between 0-269 days for 35-49 year olds, compared to 18-34 year olds. There is evidence of anti-N waning from 120 days onwards, with earlier waning for females and younger age categories. Discussion: Approximately 4 in 5 participants with prior PCR-confirmed infection were anti-N positive, and this remained stable through follow-up for at least 269 days. However, median antibody levels began to decline from about 120 days post-infection. This suggests that anti-N have around 80% sensitivity for identifying previous COVID-19 infection and that this sensitivity is maintained through 269 days of follow up.

SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men (preprint)

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. Methods We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16/11/2020 - 10/01/2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. Results Sequences were obtained from 2341 inpatients (HOCI cases = 786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The hazard ratio (HR) for mortality of B.1.1.7 compared to other lineages was 1.01 (95% CI 0.79-1.28, P=0.94) and for ITU admission was 1.01 (95% CI 0.75-1.37, P=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95-1.78) and ITU admission (HR 1.82, 95% CI 1.15-2.90) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61-1.10; ITU HR 0.74, 95% CI 0.52-1.04). Conclusions In common with smaller studies of patients hospitalised with SARS-CoV-2 we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared to other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.

Relative perceived importance of different settings for SARS-CoV2 acquisition in England and Wales: Analysis of the Virus Watch Community Cohort (preprint)

We aimed to assess the relative importance of different settings for SARS-CoV2 transmission in a large community cohort. We demonstrate the importance of home, work and education as venues for transmission. In children, education was most important and in older adults essential shopping was of high importance. Our findings support public health messaging about infection control at home, advice on working from home and restrictions in different venues.

Prevalence of persistent symptoms in children during the COVID-19 pandemic: evidence from a household cohort study in England and Wales (preprint)

Using data from 4678 children participating in VirusWatch, a UK household cohort study, we estimated the prevalence of persistent symptoms as 1.7%, and 4.6% in children with a history of SARS-CoV-2 infection. Persistent symptoms prevalence was higher in girls, teenagers and children with long-term conditions.

Occupation, Work-Related Contact, and SARS-CoV-2 Anti-Nucleocapsid Serological Status: Findings from the Virus Watch prospective cohort study (preprint)

BackgroundWorkers differ in their risk of acquiring SARS-CoV-2 infection according to their occupation; however, few studies have been able to control for multiple confounders or investigate the work-related factors that drive differences in occupational risk. Using data from the Virus Watch community cohort study in England and Wales, we set out to estimate the total effect of occupation on SARS-CoV-2 serological status, whether this is mediated by frequency of close contact within the workplace, and how exposure to poorly ventilated workplaces varied across occupations. MethodsWe used data from a sub-cohort (n =3761) of adults ([≥]18) tested for SARS-CoV-2 anti-nucleocapsid antibodies between 01 February-28 April 2021 and responded to a questionnaire about work during the pandemic. Anti-nucleocapsid antibodies were used as a proxy of prior natural infection with COVID-19. We used logistic decomposition to estimate the total and direct effect of occupation and indirect effect of workplace contact frequency on odds of seropositivity, adjusting for age, sex, household income and region. We investigated the relationship between occupation and exposure to poorly-ventilated workplace environments using ordinal logistic regression. ResultsSeropositivity was 16.0% (113/707) amongst workers with daily close contact, compared to 12.9% (120/933) for those with intermediate-frequency contact and 9.6% (203/2121) for those with no work-related close contact. Healthcare (OR= 2.14, 95% CI 1.47,3.12), indoor trade, process and plant (2.09, 1.31,3.33), leisure and personal service (1.96, 1.004,3.84), and transport and mobile machine (2.17, 1.12,4.18) workers had elevated total odds of SARS-CoV-2 seropositivity compared to other professional and associate occupations. Frequency of workplace contact accounted for a variable part of the increased odds in different occupational groups (OR range 1.04 [1.0004,1.07] - 1.22 [1.07, 1.38]). Healthcare workers and indoor trades and process plant workers continued to have raised odds of infection after accounting for work-related contact, and also had had greater odds of frequent exposure to poorly-ventilated workplaces (respectively 2.15 [1.66, 2.79] and (1.51, [1.12, 2.04]). DiscussionMarked variations in occupational odds of seropositivity remain after accounting for age, sex, region, and household income. Close contact in the workplace appears to contribute substantially to this variation. Reducing frequency of workplace contact is a critical part of COVID-19 control measures.

Deprivation and Exposure to Public Activities during the COVID-19 Pandemic in England and Wales (preprint)

Background: Differential exposure to public activities and non-household contacts may contribute to stark deprivation-related inequalities in SARS-CoV-2 infection and outcomes, but has not been directly investigated. We set out to investigate whether participants in Virus Watch - a large community cohort study based in England and Wales - reported different levels of exposure to public activities and non-household contacts during the Autumn-Winter phase of the COVID-19 pandemic according to postcode-level socioeconomic deprivation. Methods: Participants (n=20120-25228 across surveys) reported their daily activities during three weekly periods in late November 2020, late December 2020, and mid-February 2021. Deprivation was quantified based on participants' postcode of residence using English or Welsh Indices of Multiple Deprivation quintiles. We used Poisson mixed effect models with robust standard errors to estimate the relationship between deprivation and risk of exposure to public activities during each survey period. Results: Relative to participants in the least deprived areas, participants in the most deprived areas persistently exhibited elevated risk of exposure to vehicle sharing (aRR range across time points 1.73-8.52), public transport (aRR 3.13-5.73), work or education outside of the household (aRR 1.09-1.21), essential shops (aRR 1.09-1.13) and non-household contacts (aRR 1.15-1.19) across multiple survey periods. Conclusion: Differential exposure to essential public activities in deprived communities is likely to contribute to inequalities in infection risk and outcomes during the COVID-19 pandemic. Public health interventions to reduce exposure during essential activities and financial and practical support to enable low-paid workers to stay at home during periods of intense transmission may reduce COVID-related inequalities.

Covid-19 infection and attributable mortality in UK Long Term Care Facilities: Cohort study using active surveillance and electronic records (March-June 2020) (preprint)

BackgroundEpidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic. MethodsCohort study of 179 UK care homes with 9,339 residents and 11,604 staff.We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality, and estimate attributable mortality. Results2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff respectively. 121/179 (67.6%) care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection. 217/607 residents with confirmed infection died (case-fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was two-fold higher in care homes with outbreaks versus those without (adjusted HR 2.2 [1.8; 2.6]). ConclusionsFindings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.