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.

Changes in mobility pre and post first SARS-CoV-2 vaccination: findings from a prospective community cohort study including GPS movement tracking in England and Wales (Virus Watch) (preprint)

Abstract Background: Some evidence suggests that individuals may change adherence to public health policies aimed at reducing contact, transmission and spread of the SARS-CoV-2 virus after they receive their first SARS-CoV-2 vaccination. In this study, we aim to estimate the rate of change in average daily travel distance from a participant's registered address before and after SARS-CoV-2 vaccination. Method: Participants were recruited into Virus Watch starting in June 2020. Weekly surveys were sent out to participants and vaccination status was collected from January 2021 onwards. Between September 2020 and February 2021, we invited 13,120 adult Virus Watch participants to contribute towards our tracker sub-cohort which uses the Global Positioning System (GPS) to collect data on movement. We used segmented linear regression to estimate the median daily travel distance before and after the first self-reported SARS-CoV-2 vaccine dose. Results: We analysed the daily travel distance of 228 vaccinated adults. Between 157 days prior to vaccination until the day before vaccination, the median daily travel distance travelled was 8.9km (IQR: 3.50km, 24.17km). Between the day of vaccination and 100 days after vaccination, the median daily travel distance travelled was 10.30km (IQR: 4.11, 27.53km). Between 157 days prior to vaccination and the vaccination date, there was a daily median decrease in mobility of 40m (95%CI: -51m, -31m, p-value <0.001) per day. After the removal of outlier data, and between the vaccination date and 99 days after vaccination, there was a median daily increase in movement of 45.0m (95%CI: 25m, 65m, p-value = <0.001). Restricting the analysis to the 3rd national lockdown (4th of January 2021 to the 5th of April 2021), we found a median daily movement increase of 9m (95%CI: -25m, 45m, p = 0.57) in the 30 days prior to vaccination and the vaccination date, and a median daily movement increase of 10m (95%CI: -60m, 94m, p-value = 0.69) in the 30 days after vaccination. Conclusions: Our study demonstrates the feasibility of collecting high volume geolocation data as part of research projects, and the utility of these for understanding public health issues. Our results are consistent with both an increase and decrease in movement after vaccination and suggest that, amongst Virus Watch participants, any changes in movement distances post-vaccination are small.

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.

Symptom profiles and accuracy of clinical definitions for COVID-19 in the community. Results of the Virus Watch community cohort. (preprint)

Background: Understanding the symptomatology and accuracy of clinical case definitions for COVID-19 in the community is important for the initiation of Test, Trace and Isolate (TTI) and may, in future, be important for early prescription of antivirals. Methods: Virus Watch is a large community cohort with prospective daily recording of a wide range of symptoms and self-reporting of swab results (mainly undertaken through the UK TTI System). We compared frequency, severity, timing, and duration of symptoms in test positive and test negative cases. We compared the test performance of the current UK case definition used by TTI (any one of: new continuous cough, high temperature or loss of or change in sense of smell or taste) with a wider definition that also included muscle aches or chills or headache or loss of appetite. Findings: We included results from 8213 swabbed illnesses, 944 of which tested positive for COVID-19. All symptoms were more common in swab positive than swab negative illnesses and symptoms were also more severe and of longer duration. Common symptoms such as cough, headache, fatigue, muscle aches and loss of appetite occurred early in the course of illness but were also very common in test-negative illnesses. Rarer symptoms such as fever or loss or altered sense of smell or taste were often not present but were markedly more common in swab positive compared to swab negative cases. The current UK definition had a sensitivity and specificity of 81% and 47% respectively for symptomatic COVID-19 compared to 93% and 26% for the broader definition. On average cases met the broader case definition one day earlier than current definition. 1.7-fold more illnesses met the broader definition than the current case definition. Interpretation: COVID-19 is difficult to distinguish from other respiratory infections and common ailments on the basis of symptoms. Broadening the list of symptoms used to encourage engagement with TTI could moderately increase the number of infections identified and shorten delays but with a large increase in the number of tests needed and in the number of people and contacts who do not have COVID-19 but might need to self-isolate whilst awaiting results.

Spike-antibody responses to ChAdOx1 and BNT162b2 vaccines by demographic and clinical factors (Virus Watch study) (preprint)

Background Vaccination constitutes the best long-term solution against Coronavirus Disease 2019 (COVID-19). Real-world immunogenicity data are sparse, particularly for ChAdOx1 and in populations with chronic conditions; and given the UK’s extended dosing interval, it is also important to understand antibody responses in SARS-CoV-2-naive individuals following a single dose. Methods Adults aged ≥18 years from households enrolled in Virus Watch, a prospective community cohort study in England and Wales, provided capillary blood samples and self-reported vaccination status. Primary outcome variables were quantitative Spike total antibody levels (U/ml) and seropositivity to Spike (≥0.8 U/ml), as per Roche’s Elecsys Anti-SARS-CoV-2 S assay. Samples seropositive for Nucleocapsid, and samples taken prior to vaccination, were excluded. Outcomes were analysed by days since vaccination, vaccine type (BNT162b2 and ChAdOx1), and a range of self-reported demographic and clinical factors. Results 8,837 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 17,160 samples (10,508 following ChAdOx1, 6,547 following BNT162b2). Seropositivity to Spike was 96.79% (95% CI 96.42, 97.12) from 28 days following a single dose, reaching 99.34% (98.91, 99.60) from 14 days after a second dose. Seropositivity rates, and Spike-antibody levels rose more quickly following the first dose of BNT162b2, however, were equivalent for both vaccines by 4 and 8 weeks, respectively. There was evidence for lower S-antibody levels with increasing age (p=0.0001). In partially vaccinated 65-79 year-olds, lower S-antibody levels were observed in men compared with women (26.50 vs 44.01 U/ml, p<0.0001), those with any chronic condition (33.8 vs 43.83 U/ml, p<0.0001), diabetes (22.46 vs 36.90 U/ml, p<0.0001), cardiovascular disease (32.9 vs 37.9 U/ml, p=0.0002), obesity (27.2 vs 37.42, p<0.0001), cancer diagnosis (31.39 vs 36.50 U/ml, p=0.0001), particularly those with haematological cancers (7.94 vs 32.50 U/ml, p<0.0001), and for those currently on statin therapy (30.03 vs 39.39, p<0.0001), or on any immunosuppressive therapy (28.7 vs 36.78 U/ml, p<0.0001), particularly those on oral steroids (16.8 vs 36.07, p<0.0001). Following a second dose, high S-antibody titres (≥250U/ml) were observed across all groups. Interpretation A single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. Observed disparities in antibody levels by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures for partially vaccinated adults, particularly those who are older and more clinically vulnerable; and high antibody levels across all groups following a second dose demonstrate the importance of complete vaccination. However, the relationship between Spike-antibody levels and protection against COVID-19, and thus the clinical significance of observed disparities, is not yet clear.

Household overcrowding and risk of SARS-CoV-2: analysis of the Virus Watch prospective community cohort study in England and Wales (preprint)

Background: Household overcrowding is associated with increased risk of infectious diseases across cultures and countries. Limited data exist in England and Wales linking household overcrowding and risk of COVID-19. We used data collected from the Virus Watch cohort to examine the association between overcrowded households and infection to pandemic coronavirus SARS-CoV-2. Methods: The Virus Watch study is a household community cohort of acute respiratory infections in England & Wales that began recruitment in June 2020. We calculated the persons per room for each household and classified accommodation as overcrowded when the number of roomswas fewer than the number of people. We considered two primary outcomes - PCR-confirmed positive SARS-CoV-2 antigen tests and laboratory confirmed SARS-CoV-2 antibodies (Roche Elecsys anti-N total immunoglobulin assay). We used mixed effects logistic regression models that accounted for household structure to estimate the association between household overcrowding and SARS-CoV-2 infection. Results: The proportion of participants with a positive SARS-CoV-2 PCR result was highest in the overcrowded group (6.6%; 73/1,102) and lowest in the under-occupied group (2.9%; 682/23,219). In a mixed effects logistic regression model that included age, sex, ethnicity, household income and geographical region as fixed effects, and a household-level random effect, we found strong evidence of an increased odds of having a positive PCR SARS-CoV-2 antigen result (Odds Ratio 3.67; 95% CI: 1.91, 7.06; p-value < 0.001) and increased odds of having a positive SARS-CoV-2 antigen result in individuals living in overcrowded houses (2.99; 95% CI: 1.14, 7.81; p-value =0.03) compared to people living in under-occupied houses. Discussion: Public health interventions to prevent and stop the spread of SARS-CoV-2 should consider the much greater risk of infection for people living in overcrowded households and pay greater attention to reducing household transmission. There is an urgent need to better recognise housing as a leading determinant of health in the context of a pandemic and beyond.

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.

Trends, patterns and psychological influences on COVID-19 vaccination intention: findings from a large prospective community cohort study in England and Wales (Virus Watch) (preprint)

ObjectivesTo assess trends in intention to accept a COVID-19 vaccine between 1 December 2020 and 25 February 2021, explore associations between socio-demographic factors and vaccination intention and investigate how COVID-19 vaccine- and illness-related attitudes, beliefs and emotions influence vaccination intention. DesignProspective household community cohort study of COVID-19 infection (Virus Watch). SettinOnline survey of Virus Watch study participants in the community across England and Wales. ParticipantsIndividuals could enrol in Virus Watch if all household members agreed to participate and at least one household member had access to the internet, an email address, and could read English. All Virus Watch participants aged 16 years and over who responded to questions relating to COVID-19 vaccine intention in questionnaires between December 2020 and February 2021 were included in this analysis. Main outcome measuresVaccination intention was measured by individual participant responses to Would you accept a COVID-19 vaccine if offered?, collected between 1-14 December 2020 and 17-25 February 2021. Possible responses were Yes, No and Unsure (December 2020 &February 2021) and Already had a COVID-19 vaccine (February 2021 only). Responses to a 13-item questionnaire collected between 4-11 January 2021 were analysed using factor analysis to investigate psychological influences (attitudes, beliefs and emotions) on vaccination intention. ResultsSurvey response rate was 56% (20,792/36,998) in December 2020 and 52% (20,284/38,727) in February 2021, with 14,713 adults reporting across both time points. Of participants reporting across both timepoints, 13,281 (90%) answered Yes and 1,432 (10%) responded No or Unsure in December 2020. Of those answering No or Unsure in December 2020, 1,233 (86%) went on to answer Yes or Already had a COVID-19 vaccine in February 2021. The magnitude of this shift was consistent across all ethnic groups measured and all levels of social deprivation. Age was most strongly associated with vaccination intention, with 16-24-year-olds more likely to respond "No" or "Unsure" than those aged 75+ in December 2020 (RR: 4.32, 95% CI: 2.40-7.78 &2.93 95% CI: 2.19-3.92, respectively) and February 2021 (RR: 5.30 95% CI: 1.39-20.20 &20.21 95%CI: 7.19-56.78). The association between ethnicity and vaccination intention has weakened, but not disappeared, over time. Both vaccine- and illness-related psychological factors were shown to influence vaccination intention. ConclusionsOver four in five adults (86%) who were reluctant or intending to refuse a COVID-19 vaccine in December 2020 had changed their mind in February 2021 and planned on accepting, or had already accepted, a vaccine.

Risk factors, symptom reporting, healthcare-seeking behaviour and adherence to public health guidance: protocol for Virus Watch, a prospective community cohort study (preprint)

Introduction The Coronavirus (COVID-19) Pandemic has caused significant global mortality and impacted lives around the world. Virus Watch aims to provide evidence on which public health approaches are most likely to be effective in reducing transmission and impact of the virus, and will investigate community incidence, symptom profiles, and transmission of COVID-19 in relation to population movement and behaviours. Methods and analysis Virus Watch is a household community cohort study of acute respiratory infections in England & Wales and will run from June 2020 to August 2021. The study aims to recruit 50,000 people, including 12,500 from minority ethnic backgrounds, for an online survey cohort and monthly antibody testing using home finger prick kits. Nested within this larger study will be a sub-cohort of 10,000 individuals, including 3,000 people from minority ethnic backgrounds. This cohort of 10,000 people will have full blood serology taken between October 2020 and January 2021 and repeat serology between May 2021 and August 2021. Participants will also post self-administered nasal swabs for PCR assays of SARS-CoV-2 and will follow one of three different PCR testing schedules based upon symptoms. Ethics and dissemination This study has been approved by the Hampstead NHS Health Research Authority Ethics Committee. Ethics approval number – 20/HRA/2320. We are monitoring participant queries and using these to refine methodology where necessary, and are providing summaries and policy briefings of our preliminary findings to inform public health action by working through our partnerships with our study advisory group, Public Health England, NHS and Government Scientific Advisory panels. Strengths and limitations of this study Virus Watch is a large national household community cohort study of the occurrence and risk factors for COVID-19 infection that aims to recruit 50,000 people, including 12,500 from minority ethnic backgrounds. Virus Watch is designed to estimate incidence of PCR confirmed COVID-19 in those with respiratory and non-respiratory presentations and the incidence of hospitalisation among PCR confirmed COVID-19 cases. Virus Watch will measure effectiveness and impact of recommended COVID-19 control measures including testing, isolation, social distancing, respiratory and hand hygiene measures on risk of respiratory infection. Only households with a lead householder able to speak English were able to take part in the study up until March 2021. Only households of up to six people were eligible for inclusion and they were also required to have access to an internet connection. These restrictions will limit the generalisability to large or multigenerational households, and those without access to the internet.