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IntroductionSeroprevalence 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. MethodsAdults aged [≥]18 years old, 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 manufacturers 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. ResultsA 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. DiscussionApproximately 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. FundingThe research costs for the study have been supported by the MRC Grant Ref: MC_PC 19070 awarded to UCL on 30 March 2020 and MRC Grant Ref: MR/V028375/1 awarded on 17 August 2020. The study also received $15,000 of Facebook advertising credit to support a pilot social media recruitment campaign on 18th August 2020. The study also received funding from the UK Government Department of Health and Social Cares Vaccine Evaluation Programme to provide monthly Thriva antibody tests to adult participants. This study was supported by the Wellcome Trust through a Wellcome Clinical Research Career Development Fellowship to RA [206602].
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BackgroundSARS-CoV-2 vaccines stimulate production of antibodies targeting the spike protein (anti-S). The level of antibodies following vaccination and trajectories of waning may differ between vaccines influencing the level of protection, how soon protection is reduced and, consequently the optimum timing of booster doses. MethodsWe measured SARS-CoV-2 anti-S titre in the context of seronegativity for SARS-CoV-2 anti-Nucleocapsid (anti-N), in samples collected between 1st July and 24th October 2021 in a subset of adults in the Virus Watch community cohort. We compared anti-S levels after BNT162b2 (BioNTech/Pfizer) or ChAdOx1 (AstraZeneca/Oxford) vaccination using time since second dose of vaccination, age, sex and clinical vulnerability to investigate antibody waning. To investigate the use of anti-S levels as a correlate of protection against SARS-CoV-2 infection, we undertook a survival analysis (Kaplan-Meier and Cox) with individuals entering 21 days after their second dose of vaccine, or first antibody test after 1st July (whichever was latest) and exiting with the outcome of SARS-Cov-2 infection or at the end of follow up 24th October 2021. We also undertook a negative test design case-control analysis of infections occurring after the second vaccine dose (breakthrough infections) to determine whether the type of vaccine affected the risk of becoming infected. Results24049 samples from 8858 individuals (5549 who received a second dose of ChAdOx1 and 3205 BNT162b2) who remained anti-N negative were included in the analysis of anti-S waning over time. Three weeks after the second dose of vaccine BNT162b2 mean anti-S levels were 9039 (95%CI: 7946-10905) U/ml and ChadOx1 were 1025 (95%CI: 917-1146) U/ml. For both vaccines, waning anti-S levels followed a log linear decline from three weeks after the second dose of vaccination. At 20 weeks after the second dose of vaccine, the mean anti-S levels were 1521 (95%CI: 1432-1616) U/ml for BNT162b2 and 342 (95%CI: 322-365) U/ml for ChadOx1. We identified 197 breakthrough infections and found a reduced risk of infection post second dose of vaccine for individuals with anti-S levels greater than or equal to 500 U/ml compared to those with levels under 500 U/ml (HR 0.62; 95%CIs:0.44-0.87; p=0.007). Time to reach an anti-S threshold of 500 U/ml was estimated at 96 days for ChAdOx1 and 257 days for BNT162b2. We found an increased risk of a breakthrough infection for those who received the ChAdOx1 compared to those who received BNT162b2 (OR: 1.43, 95% CIs:1.18-1.73, p<0.001). DiscussionAnti-S levels are substantially higher following the second dose of BNT162b2 compared to ChAdOx1. There is a log linear waning in levels for both vaccines following the second dose. Anti-S levels are an important correlate of protection as demonstrated by those with anti-S levels < 500U/ml following vaccination being at significantly greater risk of subsequent infection. Since anti-S levels are substantially lower in ChAdOx1 than in BNT162b2 and both decline at similar rates we would expect waning immunity to occur earlier in ChAdOx1 compared to BNT162b2. Our results showing an increased risk of breakthrough infections for those who were vaccinated with ChAdOx1 compared to BNT162b2 are in line with this hypothesis. Consistent with our data, national analyses of vaccine effectiveness also suggest that waning of immunity for infection and, to a lesser extent for severe disease, is seen earlier in ChAdOx1 than in BNT162b2. Our data demonstrate the importance of booster doses to maintain protection in the elderly and clinically vulnerable and suggest that these should be prioritised to those who received ChAdOx1 as their primary course.
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BackgroundThe unprecedented public health impact of the 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 and FindingsWe develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are 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 hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. ConclusionsThere is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those 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.
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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.
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IntroductionIncreased transmissibility of B.1.17 variant of concern (VOC) in the UK may explain its rapid emergence and global spread. We analysed data from putative household infector - infectee pairs in the Virus Watch Community cohort study to assess the serial interval of COVID-19 and whether this was affected by emergence of the B.1.17 variant. MethodsThe Virus Watch study is an online, prospective, community cohort study following up entire households in England and Wales during the COVID-19 pandemic. Putative household infector-infectee pairs were identified where more than one person in the household had a positive swab matched to an illness episode. Data on whether individual infections were caused by the B.1.1.7 variant were not available. We therefore developed a classification system based on the percentage of cases estimated to be due to B.1.17 in national surveillance data for different English regions and study weeks. ResultsOut of 24,887 illnesses reported, 915 tested positive for SARS-CoV-2 and 186 likely infector-infectee pairs in 186 households amongst 372 individuals were identified. The mean COVID-19 serial interval was 3.18 (95%CI: 2.55 - 3.81) days. There was no significant difference (p=0.267) between the mean serial interval for Variants of Concern (VOC) hotspots (mean = 3.64 days, (95%CI: 2.55 - 4.73)) days and non-VOC hotspots, (mean = 2.72 days, (95%CI: 1.48 - 3.96)). ConclusionsOur estimates of the average serial interval of COVID-19 are broadly similar to estimates from previous studies and we find no evidence that B.1.1.7 is associated with a change in serial intervals. Alternative explanations such as increased viral load, longer period of viral shedding or improved receptor binding may instead explain the increased transmissibility and rapid spread and should undergo further investigation.
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BackgroundVaccination 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 UKs extended dosing interval, it is also important to understand antibody responses in SARS-CoV-2-naive individuals following a single dose. MethodsAdults 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 Roches 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. Results8,517 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 13,232 samples (8,115 following ChAdOx1, 5,008 following BNT162b2). Seropositivity to Spike was 96.42% (95%CI 96, 96.79) at 28-34 days following a single dose, reaching 99.08% (97.8, 99.62) at 7-14 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 of 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 (25.9 vs 42.3 U/ml, p<0.0001), those with a chronic condition (33.0 vs 41.2 U/ml, p<0.0001), diabetes (22.32 vs 36.01 U/ml, p<0.0001), cardiovascular disease (32.1 vs 36.7 U/ml, p=0.0002), or history of cancer (30.1 vs 35.7 U/ml, p=0.0001), particularly those with haematological rather than solid organ cancer (7.48 vs 31.68 U/ml, p<0.0001), and those currently on immunosuppressive therapy (21.7 vs 35.6 U/ml, p<0.0001). Following a second dose, high S-antibody titres ([≥]250U/ml) were observed for nearly all individuals. InterpretationA single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. However, observed disparities in antibody levels after the first dose by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures such as social distancing, for partially vaccinated adults, particularly those who are older and more clinically vulnerable.
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BackgroundDifferential 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. MethodsParticipants (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. ResultsRelative 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. ConclusionDifferential 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.
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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.
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BackgroundSignificant 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. MethodsCross-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. FindingsPoint prevalence of SARS-CoV-2 carriage across the sites was 2{middle dot}0% (23/1152 participants), median cycle threshold value 35{middle dot}70 (IQR:32{middle dot}42-37{middle dot}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{middle dot}46, 95%CI 1{middle dot}38-8{middle dot}67; p=0{middle dot}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. InterpretationThe 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. FundingPublic Health England. Word CountO_ST_ABSResearch in contextC_ST_ABSEvidence before this studyA search of PubMed was performed on 29th April 2020 to identify other major works in this field, using the search terms ("novel coronavirus" OR "SARS-CoV-2" OR "COVID-19" OR "coronavirus") AND ("workers" OR "staff") AND ("testing" OR "screening") from 31st December 2019 onwards with no other limits. This search was updated on 10th May 2020, and in addition reference lists were checked and pre-print papers were shared with us through professional networks. We found three papers commenting on prevalence of asymptomatic/pauci-symptomatic SARS-CoV-2 infection in healthcare workers, with prevalence estimates ranging from 1{middle dot}1 to 8%. One of these studies explored previous symptoms in depth, though this was based upon a retrospective questionnaire and thus subject to recall bias. None of these studies explored exposures to the SARS-CoV-2 virus, commented on whether participants had been tested prior to the start of the study, or broke down results by staff role. Only one reported on estimated viral load (as inferred from cycle threshold [Ct] value), and none reported attempting viral culture. Added value of this studyThis is the first published study of which we are aware that has been conducted across multiple sites in England and is therefore potentially more representative of the overall prevalence of SARS-CoV-2 infectivity amongst HCWs in the workplace. We explored symptoms in the preceding month in more depth than previous studies and in addition asked about previous test results and various exposures, also not commented on in other studies. Additionally, we attempted to isolate virus from some PCR-positive samples to look for evidence of infectious virus. Implications of all the available evidenceAuthors of previous studies have proposed that screening asymptomatic HCWs for SARS-CoV-2 RNA may be beneficial, in addition to screening symptomatic HCWs. Our findings suggest that when prevalence of COVID-19 is very low, routine and repeated screening would be unlikely to have significant value, especially given the majority of participants testing positive in this study were unlikely to be infectious. However, in situations where prevalence levels are high in a particular population or setting, for example in a hospital outbreak, widening the case definition, or screening all HCWs irrespective of symptoms, may be of benefit.