ABSTRACT
Real-world data on antibody response post-vaccination in the general population are limited. 45,965 adults in the UKs national COVID-19 Infection Survey receiving Pfizer-BioNTech or Oxford-AstraZeneca vaccines had 111,360 anti-spike IgG measurements. Without prior infection, seroconversion rates and quantitative antibody levels post single dose were lower in older individuals, especially >60y. Two doses achieved high responses across all ages, particularly increasing seroconversion in older people, to similar levels to those achieved after prior infection followed by a single dose. Antibody levels rose more slowly and to lower levels with Oxford-AstraZeneca vs Pfizer-BioNTech, but waned following a single Pfizer-BioNTech dose. Latent class models identified four responder phenotypes: older people, males, and those having long-term health conditions were more commonly low responders. Where supplies are limited, vaccines should be prioritised for those not previously infected, and second doses to individuals >60y. Further data on the relationship between vaccine-mediated protection and antibody responses are needed.
ABSTRACT
ObjectivesTo assess the effectiveness of COVID-19 vaccination in preventing SARS-CoV-2 infection in the community. DesignProspective cohort study. SettingThe UK population-representative longitudinal COVID-19 Infection Survey. Participants373,402 participants aged [≥]16 years contributing 1,610,562 RT-PCR results from nose and throat swabs between 1 December 2020 and 3 April 2021. Main outcome measuresNew RT-PCR-positive episodes for SARS-CoV-2 overall, by self-reported symptoms, by cycle threshold (Ct) value (<30 versus [≥]30), and by gene positivity (compatible with the B.1.1.7 variant versus not). ResultsOdds of new SARS-CoV-2 infection were reduced 65% (95% CI 60 to 70%; P<0.001) in those [≥]21 days since first vaccination with no second dose versus unvaccinated individuals without evidence of prior infection (RT-PCR or antibody). In those vaccinated, the largest reduction in odds was seen post second dose (70%, 95% CI 62 to 77%; P<0.001).There was no evidence that these benefits varied between Oxford-AstraZeneca and Pfizer-BioNTech vaccines (P>0.9).There was no evidence of a difference in odds of new SARS-CoV-2 infection for individuals having received two vaccine doses and with evidence of prior infection but not vaccinated (P=0.89). Vaccination had a greater impact on reducing SARS-CoV-2 infections with evidence of high viral shedding Ct<30 (88% reduction after two doses; 95% CI 80 to 93%; P<0.001) and with self-reported symptoms (90% reduction after two doses; 95% CI 82 to 94%; P<0.001); effects were similar for different gene positivity patterns. ConclusionVaccination with a single dose of Oxford-AstraZeneca or Pfizer-BioNTech vaccines, or two doses of Pfizer-BioNTech, significantly reduced new SARS-CoV-2 infections in this large community surveillance study. Greater reductions in symptomatic infections and/or infections with a higher viral burden are reflected in reduced rates of hospitalisations/deaths, but highlight the potential for limited ongoing transmission from asymptomatic infections in vaccinated individuals. RegistrationThe study is registered with the ISRCTN Registry, ISRCTN21086382.
ABSTRACT
BackgroundA new variant of SARS-CoV-2, B.1.1.7/VOC202012/01, was identified in the UK in December-2020. Direct estimates of its potential to enhance transmission are limited. MethodsNose and throat swabs from 28-September-2020 to 2-January-2021 in the UKs nationally representative surveillance study were tested by RT-PCR for three genes (N, S and ORF1ab). Those positive only on ORF1ab+N, S-gene target failures (SGTF), are compatible with B.1.1.7/VOC202012/01. We investigated cycle threshold (Ct) values (a proxy for viral load), percentage of positives, population positivity and growth rates in SGTF vs non-SGTF positives. Results15,166(0.98%) of 1,553,687 swabs were PCR-positive, 8,545(56%) with three genes detected and 3,531(23%) SGTF. SGTF comprised an increasing, and triple-gene positives a decreasing, percentage of infections from late-November in most UK regions/countries, e.g. from 15% to 38% to 81% over 1.5 months in London. SGTF Ct values correspondingly declined substantially to similar levels to triple-gene positives. Population-level SGTF positivity remained low (<0.25%) in all regions/countries until late-November, when marked increases with and without self-reported symptoms occurred in southern England (to 1.5-3%), despite stable rates of non-SGTF cases. SGTF positivity rates increased on average 6% more rapidly than rates of non-SGTF positives (95% CI 4-9%) supporting addition rather than replacement with B.1.1.7/VOC202012/01. Excess growth rates for SGTF vs non-SGTF positives were similar in those up to high school age (5% (1-8%)) and older individuals (6% (4-9%)). ConclusionsDirect population-representative estimates show that the B.1.1.7/VOC202012/01 SARS-CoV-2 variant leads to higher infection rates, but does not seem particularly adapted to any age group.
ABSTRACT
Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load). Of 3,312,159 nose and throat swabs taken 26-April-2020 to 13-March-2021 in the UKs national COVID-19 Infection Survey, 27,902(0.83%) were RT-PCR-positive, 10,317(37%), 11,012(40%) and 6,550(23%) for 3, 2 or 1 of the N, S and ORF1ab genes respectively, with median Ct=29.2 ([~]215 copies/ml; IQR Ct=21.9-32.8, 14-56,400 copies/ml). Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity and age. Single-gene positives almost invariably had Ct>30, but Cts varied widely in triple-gene positives, including without symptoms. Population-level Cts changed over time, with declining Ct preceding increasing SARS-CoV-2 positivity. Of 6,189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4,808(78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody-negative. Community SARS-CoV-2 Ct values could be a useful epidemiological early-warning indicator. IMPACT STATEMENTCt values from SARS-CoV-2 RT-PCR tests vary widely and over calendar time. They have the potential to be used more broadly in public testing programmes as an "early-warning" system for shifts in infectious load and hence transmission.
ABSTRACT
BackgroundDecisions regarding the continued need for control measures to contain the spread of SARS-CoV-2 rely on accurate and up-to-date information about the number of people and risk factors for testing positive. Existing surveillance systems are not based on population samples and are generally not longitudinal in design. MethodsFrom 26 April to 19 September2020, 514,794 samples from 123,497 individuals were collected from individuals aged 2 years and over from a representative sample of private households from England. Participants completed a questionnaire and nose and throat swab were taken. The percentage of individuals testing positive for SARS-CoV-2 RNA was estimated over time using dynamic multilevel regression and post-stratification, to account for potential residual non-representativeness. Potential changes in risk factors for testing positive over time were also evaluated using multilevel regression models. FindingsBetween 26 April and 19 September 2020, in total, results were available from 514,794 samples from 123,497 individuals, of which 489 were positive overall from 398 individuals. The percentage of people testing positive for SARS-CoV-2 changed substantially over time, with an initial decrease between end of April and June, followed by low levels during the summer, before marked increases end of August and September 2020. Having a patient-facing role and working outside your home were important risk factors for testing positive in the first period but not (yet) in the second period of increased positivity rates, and age (young adults) being an important driver of the second period of increased positivity rates. A substantial proportion of infections were in individuals not reporting symptoms (53%-70%, dependent on calendar time). InterpretationImportant risk factors for testing positive varied substantially between the initial and second periods of higher positivity rates, and a substantial proportion of infections were in individuals not reporting symptoms, indicating that continued monitoring for SARS-CoV-2 in the community will be important for managing the epidemic moving forwards. FundingThis study is funded by the Department of Health and Social Care. KBP, ASW, EP and JVR are supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with Public Health England (PHE) (NIHR200915). AG is supported by U.S. National Institute of Health and Office of Naval Research. ASW is also supported by the NIHR Oxford Biomedical Research Centre and by core support from the Medical Research Council UK to the MRC Clinical Trials Unit [MC_UU_12023/22] and is an NIHR Senior Investigator. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, Department of Health, or PHE. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSUnprecedented control measures, such as national lockdowns, have been widely implemented to contain the spread of SARS-CoV-2. Decisions regarding the continued need for social distancing measures in the overall population, specific subgroups and geographic areas heavily rely on accurate and up-to-date information about the number of people and risk factors for testing positive. We searched PubMed and medRxiv and bioRxiv preprint servers up to 6 June 2020 for epidemiological studies using the terms "SARS-CoV-2" and "prevalence" or "incidence" without data or language restrictions. Most studies were small or had only information about current presence of the virus for a small subset of patients, or used data not representative of the community, such as hospital admissions, deaths or self-reported symptoms. Large population-based studies, such as the current study, are required to understand risk factors and the dynamics of the epidemic. Added value of this studyThis is the first longitudinal community survey of SARS-CoV-2 infection at national and regional levels in the UK. With more than 500,000 swabs from more than 120,000 individuals this study provides robust evidence that the percentage of individuals from the general community in England testing positive for SARS-CoV-2 clearly declined between end of April and June 2020,, followed by consistently low levels during the summer, before marked increases end of August and September 2020. Risk factors for testing positive varied substantially between the initial and second periods of higher positivity rates, with having a patient-facing role and working outside your home being important risk factors in the first period but not (yet) in the second period, and age (young adults) being an important driver of the second period of increased positivity rates. Positive tests commonly occurred without symptoms being reported. Implications of all the available evidenceThe observed decline in the percentage of individuals testing positive adds to the increasing body of empirical evidence and theoretical models that suggest that the lockdown imposed on 23 March 2020 in England was associated, at least temporarily, with a decrease in infections. Important risk factors for testing positive varied substantially between the initial and second periods of higher positivity rates, and a substantial proportion of infections were in individuals not reporting symptoms, indicating that continued monitoring for SARS-CoV-2 in the community will be important for managing the epidemic moving forwards.
ABSTRACT
ObjectiveTo estimate the percentage of individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) over time in the community in England and to quantify risk factors. DesignRepeated cross-sectional surveys of population-representative households with longitudinal follow-up if consent given. SettingEngland Participants34,992 Individuals aged 2 years and over from 16,722 private residential households. Data were collected in a pilot phase of the survey between 26 April and 28 June 2020. Main outcome measuresPercentage of individuals in the community testing positive for SARS-CoV-2 RNA using throat and nose swabs. Individuals were asked about any symptoms and potential risk factors. ResultsThe percentage of people in private-residential households testing positive for SARS-CoV-2 reduced from 0.32% (95% credible interval (CrI) 0.19% to 0.52%) on 26 April to 0.08% (95% CrI 0.05% to 0.12%) on 28 June, although the prevalence stabilised near the end of the pilot. Factors associated with an increased risk of testing positive included having a job with direct patient contact (relative exposure (RE) 4.06, 95% CrI 2.42 to 6.77)), working outside the home (RE 2.49, 95% CrI 1.39 to 4.45), and having had contact with a hospital (RE 2.20, 95% CrI 1.09 to 4.16 for having been to a hospital individually and RE 1.95, 95% CrI 0.81 to 4.09 for a household member having been to a hospital). In 133 visits where individuals tested positive, 82 (61%, 95% CrI 53% to 69%) reported no symptoms, stably over time. ConclusionThe percentage of SARS-CoV-2 positive individuals declined between 26 April and 28 June 2020. Positive tests commonly occurred without symptoms being reported. Working outside your home was an important risk factor, indicating that continued monitoring for SARS-CoV-2 in the community will be essential for early detection of increases in infections following return to work and other relaxations of control measures. What is already known on this topic- Unprecedented control measures, such as national lockdowns, have been widely implemented to contain the spread of SARS-CoV-2. - Previous mass surveillance has been based on data sources such as hospital admission, deaths or self-reported symptoms that do not measure community prevalence of virus directly. - Decisions regarding the continued need for social distancing measures in the overall population, specific subgroups and geographic areas heavily rely on accurate and up-to-date information about the number of people and risk factors for testing positive. What this study adds- The percentage of individuals from the general community in England testing positive for SARS-CoV-2 clearly declined between 26 April and 28 June 2020 from around one in three 300 to around one in a thousand. - Risk factors for testing positive included having a job with direct patient contact, having had (indirect) contact with a hospital in the past 2 weeks, and working outside your home. - Positive tests commonly occurred without symptoms being reported and the percentage of individuals with a positive test that reported no symptoms was stable over time.
