Spike-antibody responses to COVID-19 vaccination by demographic and clinical factors in a prospective community cohort study.

Vaccination constitutes the best long-term solution against Coronavirus Disease-2019; however, vaccine-derived immunity may not protect all groups equally, and the durability of protective antibodies may be short. We evaluate Spike-antibody responses following BNT162b2 or ChAdOx1-S vaccination amongst SARS-CoV2-naive adults across England and Wales enrolled in a prospective cohort study (Virus Watch). Here we show BNT162b2 recipients achieved higher peak antibody levels after two doses; however, both groups experience substantial antibody waning over time. In 8356 individuals submitting a sample ≥28 days after Dose 2, we observe significantly reduced Spike-antibody levels following two doses amongst individuals reporting conditions and therapies that cause immunosuppression. After adjusting for these, several common chronic conditions also appear to attenuate the antibody response. These findings suggest the need to continue prioritising vulnerable groups, who have been vaccinated earliest and have the most attenuated antibody responses, for future boosters.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Nucleocapsid and spike antibody responses following virologically confirmed SARS-CoV-2 infection: an observational analysis in the Virus Watch community cohort.

OBJECTIVES: Seroprevalence studies can provide a measure of SARS-CoV-2 cumulative incidence, but a better understanding of spike and nucleocapsid (anti-N) antibody dynamics following infection is needed to assess the longevity of detectability. METHODS: Adults aged ≥18 years, from households enrolled in the Virus Watch prospective community cohort study in England and Wales, provided monthly capillary blood samples, which were tested for spike antibody and anti-N. Participants self-reported vaccination dates and past medical history. Previous polymerase chain reaction (PCR) swabs were obtained through Second Generation Surveillance System linkage data. The primary outcome variables were seropositivity and total anti-N and spike antibody levels after PCR-confirmed infection. RESULTS: A total of 13,802 eligible individuals provided 58,770 capillary blood samples. A total of 537 of these had a previous positive PCR-confirmed SARS-CoV-2 infection within 0-269 days of antibody sample date, among them 432 (80.45%) having a positive anti-N result. Median anti-N levels peaked between days 90 and 119 after PCR results and then began to decline. There is evidence of anti-N waning from 120 days onwards, with earlier waning for females and younger age categories. CONCLUSION: Our findings suggest that anti-N has around 80% sensitivity for identifying previous COVID-19 infection, and the duration of detectability is affected by sex and age.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

SARS-CoV-2 antibodies and breakthrough infections in the Virus Watch cohort.

A range of studies globally demonstrate that the effectiveness of SARS-CoV-2 vaccines wane over time, but the total effect of anti-S antibody levels on risk of SARS-CoV-2 infection and whether this varies by vaccine type is not well understood. Here we show that anti-S levels peak three to four weeks following the second dose of vaccine and the geometric mean of the samples is nine fold higher for BNT162b2 than ChAdOx1. Increasing anti-S levels are associated with a reduced risk of SARS-CoV-2 infection (Hazard Ratio 0.85; 95%CIs: 0.79-0.92). We do not find evidence that this antibody relationship with risk of infection varies by second dose vaccine type (BNT162b2 vs. ChAdOx1). In keeping with our anti-S antibody data, we find that people vaccinated with ChAdOx1 had 1.64 times the odds (95% confidence interval 1.45-1.85) of a breakthrough infection compared to BNT162b2. We anticipate our findings to be useful in the estimation of the protective effect of anti-S levels on risk of infection due to Delta. Our findings provide evidence about the relationship between antibody levels and protection for different vaccines and will support decisions on optimising the timing of booster vaccinations and identifying individuals who should be prioritised for booster vaccination, including those who are older, clinically extremely vulnerable, or received ChAdOx1 as their primary course. Our finding that risk of infection by anti-S level does not interact with vaccine type, but that individuals vaccinated with ChAdOx1 were at higher risk of infection, provides additional support for the use of using anti-S levels for estimating vaccine efficacy.

Occupation, work-related contact and SARS-CoV-2 anti-nucleocapsid serological status: findings from the Virus Watch prospective cohort study.

OBJECTIVES: Risk of SARS-CoV-2 infection varies across occupations; however, investigation into factors underlying differential risk is limited. We aimed to estimate the total effect of occupation on SARS-CoV-2 serological status, whether this is mediated by workplace close contact, and how exposure to poorly ventilated workplaces varied across occupations. METHODS: We used data from a subcohort (n=3775) of adults in the UK-based Virus Watch cohort study who were tested for SARS-CoV-2 anti-nucleocapsid antibodies (indicating natural infection). We used logistic decomposition to investigate the relationship between occupation, contact and seropositivity, and logistic regression to investigate exposure to poorly ventilated workplaces. RESULTS: Seropositivity was 17.1% among workers with daily close contact vs 10.0% for those with no work-related close contact. Compared with other professional occupations, healthcare, indoor trade/process/plant, leisure/personal service, and transport/mobile machine workers had elevated adjusted total odds of seropositivity (1.80 (1.03 to 3.14) - 2.46 (1.82 to 3.33)). Work-related contact accounted for a variable part of increased odds across occupations (1.04 (1.01 to 1.08) - 1.23 (1.09 to 1.40)). Occupations with raised odds of infection after accounting for work-related contact also had greater exposure to poorly ventilated workplaces. CONCLUSIONS: Work-related close contact appears to contribute to occupational variation in seropositivity. Reducing contact in workplaces is an important COVID-19 control measure.

Deprivation and exposure to public activities during the COVID-19 pandemic in England and Wales.

BACKGROUND: Differential exposure to public activities 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 differential 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=20 120-25 228 across surveys) reported their daily activities during 3 weekly periods in late November 2020, late December 2020 and mid-February 2021. Deprivation was quantified based on participants' residential postcode using English or Welsh Index 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 exhibited elevated risk of exposure to vehicle sharing (adjusted risk ratio (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-such as attending workplaces and visiting essential shops-is likely to contribute to inequalities in infection risk and outcomes. 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).

BACKGROUND: Vaccination intention is key to the success of any vaccination programme, alongside vaccine availability and access. Public intention to take a COVID-19 vaccine is high in England and Wales compared to other countries, but vaccination rate disparities between ethnic, social and age groups has led to concern. METHODS: Online survey of prospective household community cohort study participants across England and Wales (Virus Watch). Vaccination intention was measured by individual participant responses to 'Would you accept a COVID-19 vaccine if offered?', collected in December 2020 and February 2021. Responses to a 13-item questionnaire collected in January 2021 were analysed using factor analysis to investigate psychological influences on vaccination intention. RESULTS: Survey response rate was 56% (20,785/36,998) in December 2020 and 53% (20,590/38,727) in February 2021, with 14,880 adults reporting across both time points. In December 2020, 1,469 (10%) participants responded 'No' or 'Unsure'. Of these people, 1,266 (86%) changed their mind and responded 'Yes' or 'Already had a COVID-19 vaccine' by February 2021. Vaccination intention increased across all ethnic groups and levels of social deprivation. Age was most strongly associated with vaccination intention, with 16-24-year-olds more likely to respond "Unsure" or "No" versus "Yes" than 65-74-year-olds in December 2020 (OR: 4.63, 95 %CI: 3.42, 6.27 & OR 7.17 95 %CI: 4.26, 12.07 respectively) and February 2021 (OR: 27.92 95 %CI: 13.79, 56.51 & OR 17.16 95 %CI: 4.12, 71.55). The association between ethnicity and vaccination intention weakened, but did not disappear, over time. Both vaccine- and illness-related psychological factors were shown to influence vaccination intention. CONCLUSIONS: 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 to accept, 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.

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 and 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 fingerprick test kits. Nested within this larger study will be a subcohort of 10 000 individuals, including 3000 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 on symptoms. ETHICS AND DISSEMINATION: This study has been approved by the Hampstead National Health Service (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.

Persistence of SARS-CoV-2 N-Antibody Response in Healthcare Workers, London, UK.

Prospective serosurveillance of severe acute respiratory syndrome coronavirus 2 in 1,069 healthcare workers in London, UK, demonstrated that nucleocapsid antibody titers were stable and sustained for <12 weeks in 312 seropositive participants. This finding was consistent across demographic and clinical variables and contrasts with reports of short-term antibody waning.

Snapshot PCR surveillance for SARS-CoV-2 in hospital staff in England.

BACKGROUND: Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread. METHODS: Cross-sectional 'snapshot' survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples. FINDINGS: Point prevalence of SARS-CoV-2 carriage across the sites was 2.0% (23/1152 participants), median cycle threshold value 35.70 (IQR:32.42-37.57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3.46, 95%CI 1.38-8.67; p = 0.008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month. INTERPRETATION: The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests. FUNDING: Public Health England.