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BackgroundThe SARS-CoV-2 Delta variant has been replaced by the highly transmissible Omicron BA.1 variant, and subsequently by Omicron BA.2. It is important to understand how these changes in dominant variants affect reported symptoms, while also accounting for symptoms arising from other co-circulating respiratory viruses. MethodsIn a nationally representative UK community study, the COVID-19 Infection Survey, we investigated symptoms in PCR-positive infection episodes vs. PCR-negative study visits over calendar time, by age and vaccination status, comparing periods when the Delta, Omicron BA.1 and BA.2 variants were dominant. ResultsBetween October-2020 and April-2022, 120,995 SARS-CoV-2 PCR-positive episodes occurred in 115,886 participants, with 70,683 (58%) reporting symptoms. The comparator comprised 4,766,366 PCR-negative study visits (483,894 participants); 203,422 (4%) reporting symptoms. Symptom reporting in PCR-positives varied over time, with a marked reduction in loss of taste/smell as Omicron BA.1 dominated, maintained with BA.2 (44%/45% 17 October 2021, 16%/13% 2 January 2022, 15%/12% 27 March 2022). Cough, fever, shortness of breath, myalgia, fatigue/weakness and headache also decreased after Omicron BA.1 dominated, but sore throat increased, the latter to a greater degree than concurrent increases in PCR-negatives. Fatigue/weakness increased again after BA.2 dominated, although to a similar degree to concurrent increases in PCR-negatives. Symptoms were consistently more common in adults aged 18-65 years than in children or older adults. ConclusionsIncreases in sore throat (also common in the general community), and a marked reduction in loss of taste/smell, make Omicron harder to detect with symptom-based testing algorithms, with implications for institutional and national testing policies. SummaryIn a UK community study, loss of taste/smell was markedly less commonly reported with Omicron BA.1/BA.2 than Delta SARS-CoV-2 infections, with smaller declines in reported shortness of breath, myalgia and fatigue/weakness, but increases in sore throat, challenging symptom-based testing algorithms.
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BackgroundThe COVID-19 pandemic is rapidly evolving, with emerging variants and fluctuating control policies. Real-time population screening and identification of groups in whom positivity is highest could help monitor spread and inform public health messaging and strategy. MethodsTo develop a real-time screening process, we included results from nose and throat swabs and questionnaires taken 19 July 2020-17 July 2021 in the UKs national COVID-19 Infection Survey. Fortnightly, associations between SARS-CoV-2 positivity and 60 demographic and behavioural characteristics were estimated using logistic regression models adjusted for potential confounders, considering multiple testing, collinearity, and reverse causality. FindingsOf 4,091,537 RT-PCR results from 482,677 individuals, 29,903 (0{middle dot}73%) were positive. As positivity rose September-November 2020, rates were independently higher in younger ages, and those living in Northern England, major urban conurbations, more deprived areas, and larger households. Rates were also higher in those returning from abroad, and working in healthcare or outside of home. When positivity peaked December 2020-January 2021 (Alpha), high positivity shifted to southern geographical regions. With national vaccine roll-out from December 2020, positivity reduced in vaccinated individuals. Associations attenuated as rates decreased between February-May 2021. Rising positivity rates in June-July 2021 (Delta) were independently higher in younger, male, and unvaccinated groups. Few factors were consistently associated with positivity. 25/45 (56%) confirmed associations would have been detected later using 28-day rather than 14-day periods. InterpretationPopulation-level demographic and behavioural surveillance can be a valuable tool in identifying the varying characteristics driving current SARS-CoV-2 positivity, allowing monitoring to inform public health policy. FundingDepartment of Health and Social Care (UK), Welsh Government, Department of Health (on behalf of the Northern Ireland Government), Scottish Government, National Institute for Health Research.
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The effectiveness of BNT162b2, ChAdOx1, and mRNA-1273 vaccines against new SARS-CoV-2 infections requires continuous re-evaluation, given the increasingly dominant Delta variant. We investigated the effectiveness of the vaccines in a large community-based survey of randomly selected households across the UK. We found that the effectiveness of BNT162b2 and ChAd0x1 against any infections (new PCR positives) and infections with symptoms or high viral burden is reduced with the Delta variant. A single dose of the mRNA-1273 vaccine had similar or greater effectiveness compared to a single dose of BNT162b2 or ChAdOx1. Effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity following second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positives but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher among those vaccinated following a prior infection and younger adults. With Delta, infections occurring following two vaccinations had similar peak viral burden to those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with Delta.
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BackgroundSeveral community-based studies have assessed the ability of different symptoms to identify COVID-19 infections, but few have compared symptoms over time (reflecting SARS-CoV-2 variants) and by vaccination status. MethodsUsing data and samples collected by the COVID-19 Infection Survey at regular visits to representative households across the UK, we compared symptoms in new PCR-positives and comparator test-negative controls. ResultsFrom 26/4/2020-7/8/2021, 27,869 SARS-CoV-2 PCR-positive episodes occurred in 27,692 participants (median 42 years (IQR 22-58)); 13,427 (48%) self-reported symptoms ("symptomatic positive episodes"). The comparator group comprised 3,806,692 test-negative visits (457,215 participants); 130,612 (3%) self-reported symptoms ("symptomatic negative visit"). Reporting of any symptoms in positive episodes varied over calendar time, reflecting changes in prevalence of variants, incidental changes (e.g. seasonal pathogens, schools re-opening) and vaccination roll-out. There was a small increase in sore throat reporting in symptomatic positive episodes and negative visits from April-2021. After May-2021 when Delta emerged there were substantial increases in headache and fever in positives, but not in negatives. Although specific symptom reporting in symptomatic positive episodes vs. negative visits varied by age, sex, and ethnicity, only small improvements in symptom-based infection detection were obtained; e.g. adding fatigue/weakness or all eight symptoms to the classic four symptoms (cough, fever, loss of taste/smell) increased sensitivity from 74% to 81% to 90% but tests per positive from 4.6 to 5.3 to 8.7. ConclusionsWhilst SARS-CoV-2-associated symptoms vary by variant, vaccination status and demographics, differences are modest and do not warrant large-scale changes to targeted testing approaches given resource implications. SummaryWithin the COVID-19 Infection Survey, recruiting representative households across the UK general population, SARS-CoV-2-associated symptoms varied by viral variant, vaccination status and demographics. However, differences are modest and do not currently warrant large-scale changes to targeted testing approaches.
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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.
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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.
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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.
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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.
