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1.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22275126

RESUMEN

BackgroundSARS-CoV-2 vaccine coverage remains incomplete, being only 15% in low income countries. Rapid point of care tests predicting SARS-CoV-2 infection susceptibility in the unvaccinated might assist in risk management and vaccine prioritisation. MethodsWe conducted a prospective cohort study in 2,826 participants working in hospitals and Fire and Police services in England, UK, during the pandemic (ISRCTN5660922). Plasma taken at recruitment in June 2020 was tested using four lateral flow immunoassay (LFIA) devices and two laboratory immunoassays detecting antibodies against SARS-CoV-2 (UK Rapid Test Consortiums AbC-19 Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test; Roche N and EUROIMMUN S laboratory assays). We monitored participants for microbiologically-confirmed SARS-CoV-2 infection for 200 days. We estimated associations between test results at baseline and subsequent infection, using Poisson regression models adjusted for baseline demographic risk factors for SARS-CoV-2 exposure. FindingsPositive IgG results on each of the four LFIAs were associated with lower rates of subsequent infection: adjusted incidence rate ratios (aIRRs) 0.00 (95% confidence interval 0.00-0.01), 0.03 (0.02-0.05), 0.07 (0.05-0.10), and 0.09 (0.07-0.12) respectively. The protective association was strongest for AbC-19 and SureScreen. The aIRR for the laboratory Roche N antibody assay at the manufacturer-recommended threshold was similar to those of the two best performing LFIAs at 0.03 (0.01-0.10). InterpretationLateral flow devices measuring SARS-CoV-2 IgG predicted disease risk in unvaccinated individuals over 200 day follow-up. The association of some LFIAs with subsequent infection was similar to laboratory immunoassays. FundingUK Government Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for research articles, using the search terms ("COVID-19" OR "SARS-CoV-2" OR "2019-nCoV" OR "coronavirus") AND ("Antibody" OR "IgG") AND (("protection" OR "infection") identifying studies of cohorts of unvaccinated individuals which reported antibody-associated disease protection published between Dec 1 2019 and 1 April 2022. Additionally, we reviewed studies matching "SARS-CoV-2" and "lateral flow" and "antibody" over the same period. Multiple cohort studies in healthy populations have demonstrated an association between the detection of antibodies to SARS-CoV-2 following natural infection and protection from subsequent symptomatic infection with SARS-CoV-2. Protection estimates were about 85% protection in two overlapping meta-analyses, while in several larger studies increased protection with higher antibody levels was observed. Lateral flow immunoassays (LFIAs) detecting anti-SARS-CoV-2 IgG are a cheap, readily deployed technology which has been used on a large scale in population screening programs. However, there are wide variations in sensitivity and specificity of antibody detection between different devices. No studies have investigated whether LFIA results are associated with subsequent SARS-CoV-2 infection. Added value of this studyIn a prospective cohort study of 2,826 UK key workers, we found positivity in lateral flow test results had a strong negative association with subsequent SARS-CoV-2 infection within 200 days in an unvaccinated population. The performance of different devices in predicting disease protection differed: positivity on more specific but less sensitive tests was associated with markedly decreased rate of disease. By contrast, protection associated with testing positive using more sensitive devices detecting lower levels of anti-SARS-CoV-2 IgG was more modest. Implications of all the available evidenceIf the field performance of these tests against contemporary SARS-CoV-2 infection was similar to that observed in this study, lateral flow tests with high specificity may have a role in estimation of SARS-CoV-2 disease risk in unvaccinated populations and individuals.

2.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22275053

RESUMEN

ObjectiveIn September 2020, records of 15,861 SARS-CoV-2 cases failed to upload from the Second Generation Laboratory Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, resulting in a delay in the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on health outcomes: transmission events, hospitalisations, and mortality. Previously, a modelling study had suggested a substantial impact. DesignObservational study SettingEngland. PopulationIndividuals testing positive for SARS-CoV-2 and their reported contacts. Main outcome measuresSecondary attack rates (SARs), hospitalisations, and deaths amongst primary and secondary contacts were calculated, compared to all other concurrent, unaffected cases. SGSS records affected by the event were matched to CTAS records and successive contacts and cases were identified. ResultsThe initiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared to the control group (3 days). This was associated with lower completion of contact tracing of primary cases in the delay group: 80% (95%CI: 79-81%) in the delay group and 83% (95%CI: 83-84%) in the control group. There was some evidence to suggest an increase in transmission to non-household contacts amongst those affected by the delay. The SAR for non-household contacts was higher amongst secondary contacts in the delay group than the control group (delay group: 7.9%, 95%CI:6.4% to 9.2%; control group: 5.9%, 95%CI: 5.3% to 6.6%). There was no evidence of a difference between the delay and control groups in the odds of hospitalisation (crude odds ratio: 1.1 (95%CI: 0.9 to 1.2) or death (crude odds ratio: 0.7 (0.1 to 4.0)) amongst secondary contacts. ConclusionsThe delay in contact tracing had a limited impact on population health outcomes. Strengths and limitations of the studyO_LIShows empirical data on the health impact of an event leading to a delay in contact tracing so can test hypotheses generated by models of the potential impact of a delay in contact tracing C_LIO_LIEstimates the extent of further transmission and odds of increased mortality or hospitalisation in up to the third generation of cases affected by the event C_LIO_LIThe event acts as a natural experiment to describe the possible impact of contact tracing, comparing a group affected by chance by delayed contact tracing to a control group who experienced no delay C_LIO_LIContact tracing was not completed for all individuals, so the study might not capture all affected contacts or transmissions C_LI

3.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22272273

RESUMEN

ObjectiveTo gain a better understanding of decisions around adherence to self-isolation advice during the first phase of the COVID-19 response in England. DesignA mixed-methods cross sectional study. Setting: EnglandParticipants COVID-19 cases and contacts who were contacted by Public Health England (PHE) during the first phase of the response in England (January-March 2020). ResultsOf 250 respondents who were advised to self-isolate, 63% reported not leaving home at all during their isolation period, 20% reported leaving only for lower risk activities (dog walking or exercise) and 16% reported leaving for potentially higher risk, reasons (shopping, medical appointments, childcare, meeting family or friends). Factors associated with adherence to never going out included: the belief that following isolation advice would save lives, experiencing COVID-19 symptoms, being advised to stay in their room (rather than just "inside"), having help from outside and having regular contact by text message from PHE. Factors associated with non-adherence included being angry about the advice to isolate, being unable to get groceries delivered and concerns about losing touch with friends and family. Interviews highlighted that a sense of duty motivated people to adhere to isolation guidance and where people did leave their homes, these decisions were based on rational calculations of the risk of transmission - people would only leave their homes when they thought they were unlikely to come into contact with others. ConclusionsMeasures of adherence should be nuanced to allow for the adaptations people make to their behaviour during isolation. Understanding adherence to isolation and associated reasoning during the early stages of the pandemic is an essential part of pandemic preparedness for future emerging infectious diseases. Strengths and limitations of this studyO_LIOur participants were contacted directly by Public Health England during the first three months of the pandemic - the only cohort of cases and contacts who experienced self-isolation during this early phase of the pandemic. C_LIO_LIResults may not be directly generalisable to wider populations or later phases of pandemic response. C_LIO_LIWe classified reasons for leaving the home as higher or lower contact, as a proxy for potential risk of transmission, however further research published since we conducted our research as refined our understanding of transmission risk, highlighting the need for more in-depth research on adherence behaviour and transmission risk. C_LIO_LIThe mixed methods approach combined quantitative measures of adherence with an exploration of how and why these decisions were being made in the same people. C_LIO_LIOur study provides unique insights into self-isolation during the earliest stages of the pandemic, against a background of uncertainty and lack of information that will recur, inevitably, in the face of future pandemic and similar threats. C_LI

4.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21267257

RESUMEN

BackgroundIn July 2021, a randomised controlled trial was conducted to compare the effect on SARS-CoV-2 transmission of seven days of daily contact testing (DCT) using lateral flow devise (LFT) and 2 PCR tests as an alternative to 10 days of standard self-isolation with 1 PCR, following close contact with a confirmed case of COVID-19. DCT appeared equivalent to self-isolation in terms of transmission in the trial, however it was not clear how tests were viewed and used in practice. In this qualitative study, we used a nested process to aid interpretation of the trial and provide insight into factors influencing use of tests, understanding of test results, and how tests were used to inform behavioural decisions. MethodsInterviews were conducted with 60 participants (42 randomised to DCT and 18 randomised to self-isolation) who had been in close contact with a confirmed positive case of COVID-19 and had consented to take part in the trial. ResultsSub-themes emerging from the data were organised into three overarching themes: (1) assessing the risks and benefits of DCT; (2) use of testing during the study period and (3) future use of testing. Attitudes toward DCT as an alternative to self-isolation, and behaviour during the testing period appeared to be informed by an assessment of the associated risks and benefits. Participants reported how important it was for them to avoid isolation, how necessary self-isolation was considered to be, and the ability of LFTs to detect infection. Behaviour during the testing period was modified to reduce risks and harms as much as possible. Testing was considered a potential compromise, reducing both risk of transmission and the negative impact of self-isolation and was highly regarded as a way to return to new normal. ConclusionParticipants in this study viewed DCT as a sensible, feasible and welcome means of avoiding unnecessary self-isolation. Although negative LFTs provided reassurance, most people still restricted their activity as recommended. DCT was also highly valued by those in vulnerable households as a means of providing reassurance of the absence of infection, and as an important means of detecting infection and prompting self-isolation when necessary.

5.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21268251

RESUMEN

ObjectiveExplore the impact and responses to public health advice on the health and wellbeing of individuals identified as clinically extremely vulnerable (CEV) and advised to shield (not leave home for 12 weeks at start of the pandemic) in Southwest England during the first COVID-19 lockdown. DesignMixed-methods study; structured survey and follow-up semi-structured interviews. SettingCommunities served by Bristol, North Somerset & South Gloucestershire Clinical Commissioning Group. Participants204 people (57% female, 54% >69 years, 94% White British, 64% retired) in Southwest England identified as CEV and were advised to shield completed the survey. Thirteen survey respondents participated in follow-up interviews (53% female, 40% >69years, 100% White British, 61% retired). ResultsReceipt of official communication from NHS England or General Practitioner (GP) was considered by participants as the legitimate start of shielding. 80% of survey responders felt they received all relevant advice needed to shield, yet interviewees criticised the timing of advice and often sought supplementary information. Shielding behaviours were nuanced, adapted to suit personal circumstances, and waned over time. Few interviewees received community support, although food boxes and informal social support were obtained by some. Worrying about COVID-19 was common for survey responders (90%). Since shielding had begun, physical and mental health reportedly worsened for 35% and 42% of survey responders respectively. 21% of survey responders scored [≥]10 on the PHQ-9 questionnaire indicating possible depression and 15% scored [≥]10 on the GAD-7 questionnaire indicating possible anxiety. ConclusionsThis research highlights the difficulties in providing generic messaging that is applicable and appropriate given the diversity of individuals identified as CEV and the importance of sharing tailored and timely advice to inform shielding decisions. Providing messages that reinforce self-determined action and assistance from support services could reduce the negative impact of shielding on mental health and feelings of social isolation. O_TEXTBOXStrengths and limitations of this study O_LIThe mixed-methods study examines the experiences of clinically extremely vulnerable (CEV) people at the height of the COVID-19 crisis, immediately after the first lockdown in England. C_LIO_LIThe use of an existing list of individuals identified as needing to "shield" from Bristol, North Somerset & South Gloucestershire (BNSSG) Clinical Commissioning Group (CCG) allowed for access to key patient groups at the height of the crisis. C_LIO_LIFindings may not be applicable to wider CEV populations due to demographic bias. C_LI C_TEXTBOX

6.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21268325

RESUMEN

BackgroundThe aim of this work was to explore barriers and facilitators to uptake of COVID-19 vaccines and to explore views and reactions to efforts to improve vaccine uptake among those who were vaccine hesitant. MethodsSemi-structured interviews were conducted with people between the age of 18-29 years who had not had a COVID-19 vaccine, and those between 30-49 years who had not received a second dose of a COVID-19 vaccine (more than 12 weeks after receiving a first). ResultsA total of 70 participants took part in the study, 35 participants had received one dose of the vaccine, and 35 had not received any vaccine. Participants described a possible willingness to be vaccinated to keep themselves and those around them safe, and to avoid restrictions and return to normal. Barriers to uptake included: 1) perceived lack of need for COVID-19 vaccinations, 2) concerns about the efficacy of vaccinations, 3) concerns about safety, and 4) access issues. Uptake appeared to be influenced by the age and health status of the individual, trust in government and knowledge and understanding of science. Introduction of vaccine passes may provide a motive for having a vaccine but may also be viewed as coercive. ConclusionParticipants were hesitant, rather than opposed, and had questions about their need for, and the safety and efficacy of the vaccine. Young people did not consider themselves to be at risk of becoming ill from COVID-19, did not think the vaccination was effective in preventing infection and transmission, and did not think sufficient research had been conducted with regard to the possible long-term side-effects. These concerns were exacerbated by a lack of trust in the government, and misunderstanding of science. In order to promote uptake, public health campaigns should focus on the provision of information from trusted sources that carefully explains the benefits of vaccination and addresses safety concerns more effectively. To overcome inertia in people with low levels of motivation to be vaccinated, appointments must be easily accessible.

7.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21261333

RESUMEN

ObjectivePublic health control measures at borders have long been central to national strategies for the prevention and containment of infectious diseases. Travel was inevitably associated with the rapid global transmission of COVID-19. In the UK, public health authorities took action to reduce risks of travel-associated spread by providing public health information at ports of entry. This study aims to understand individual risk assessment processes, decision making, and adherence to official advice among international travellers; to provide evidence to inform future policy on the presentation of public health information to facilitate safer international travel. Study designThis study is a qualitative study evaluation. MethodSemi-structured interviews were conducted to investigate risk assessment processes, decision making, and adherence to official Public Health England (PHE) advice among travellers. ResultsParticipants regarded official advice as adequate at the time, despite observing differences between the intervention measures implemented in the countries of departure. Participants however also described adopting precautionary measures including self-isolation and the use of face coverings that went beyond official advice, and variability in the extent to which they adhered to guidance on contacting health authorities. Adherence to official guidance was informed by the perceived salience of specific transmission possibilities and containment measures assessed in relation to participants social and institutional environments. ConclusionAnalysis of travellers reported motivations demonstrates that responses to public health advice constitute a proactive process of risk assessment and rationalised decision-making that incorporates consideration of living situation, trust in information sources, correspondence with cultural logics, and willingness to accept potential risk to self and significant others in guiding preventive action. Our findings concerning international passengers understanding of, and compliance with, official advice and mitigation measures provide valuable evidence to inform future policy and we provide recommendations on the presentation of public health information to facilitate safer international travel. Access to a central source of regularly updated official information would help minimise confusion between different national guidelines. Greater attention to the differentiated information needs of diverse groups in creating future public-facing guidance would help to minimise the uncertainties generated by receipt of generic information.

8.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21257644

RESUMEN

IntroductionIn December 2020 and January 2021 Public Health England (PHE) with NHS Test and Trace conducted a study to explore the feasibility and acceptability of daily testing as an alternative to self-isolation following close contact with a confirmed COVID-19 case. This qualitative paper aims to identify factors influencing uptake among those offered daily testing, and the subsequent impact on behaviour. MethodsWe conducted in-depth interviews with 52 participants who had taken part in the feasibility study. Participants were asked about their experiences of daily testing or self-isolating, their reasons for choosing to test or isolate, and their behaviour during the study period. Data were analysed using inductive thematic analysis. ResultsResults are presented under two main headings: 1) factors influencing acceptance of testing and 2) impact of test results. Participants appeared highly motivated to engage in behaviours that would protect others from the virus. Factors influencing the decision to accept testing included 1) needing to avoid self-isolation 2) concerns about test sensitivity and 3) perceived benefits of detecting infection. Participants who were taking tests reported:1) positive consequences following confirmation of COVID status 2) engaging in essential activities 3) uncertainty and 4) self-isolating whilst testing. ConclusionsThis study has identified a range of factors that appear to influence the decision to engage in daily testing or to self-isolate following close contact with a positive case, many of which could be addressed by clear communications. Covid-19 infection rates and government restrictions influenced experiences, and so further research is needed to explore perceptions of daily testing and behaviour following close contact with a positive case among a wider range of individuals, in the context of lower rates of COVID-19, few government restrictions on general population behaviour and more widespread testing.

9.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21254174

RESUMEN

ObjectiveTo establish the impact of the first six months of the COVID-19 outbreak response of gastrointestinal (GI) infection trends in England. DesignRetrospective ecological study using routinely collected national and regional surveillance data from eight Public Health England coordinated laboratory, outbreak and syndromic surveillance systems using key dates of UK governmental policy change to assign phases for comparison between 2020 and historic data. ResultsDecreases in GI illness activity were observed across all surveillance indicators as COVID-19 cases began to peak. Compared to the 5-year average (2015-2019), during the first six months of the COVD-19 response, there was a 52% decrease in GI outbreaks reported (1,544 vs. 3,208 (95% CI: 2,938 - 3,478) and a 34% decrease in laboratory confirmed cases (27,859 vs. 42,495 (95% CI: 40,068 - 44,922). GI indicators began to rise during the first lockdown and lockdown easing, although all remained substantially lower than historic figures. Reductions in laboratory confirmed cases were observed across all age groups and both sexes, with geographical heterogeneity observed in diagnosis trends. Health seeking behaviour changed substantially, with attendances decreasing prior to lockdown across all indicators. ConclusionsThere has been a marked change in trends of GI infections in the context of the COVID-19 pandemic. The drivers of this change are likely to be multifactorial; while changes in health seeking behaviour, pressure on diagnostic services and surveillance system ascertainment have undoubtably played a role there has likely been a true decrease in the incidence for some pathogens resulting from the control measures and restrictions implemented. This suggests that if some of these changes in behaviour such as improved hand hygiene were maintained, then we could potentially see sustained reductions in the burden of GI illness. Strengths and limitations of this studyO_LIOur findings show that there has been a marked change in the burden of GI infections during the COVID-19 outbreak, and although undoubtably changes to health care and surveillance ascertainment have played a role, there does appear to be a true decrease in incidence. These findings suggest that if effective implementation of infection control measures were maintained, then we could see sustained reductions in the person to person transmission of GI illness in England. C_LIO_LIThis study was strengthened by the triangulation of data from several national and regional-based surveillance systems; using this approach we could determine that the trends observed were consistent across all indicators. C_LIO_LIIt has not been possible to definitively differentiate the relative contributions of the reduced ascertainment of GI infections versus a true decrease in GI disease burden in this study, which an additional focussed analysis could address. C_LIO_LIThis analysis includes only the first six-months of the COVID-19 outbreak response, and further longitudinal analyses will be performed to explore this further and assess any change as we move into further phases of the pandemic C_LI

10.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21254168

RESUMEN

BackgroundTesting asymptomatic contacts of confirmed COVID-19 cases for the presence of SARS-CoV-2 could reduce onward transmission by improving case ascertainment and lessen the impact of self-isolation on un-infected individuals. This study investigated the feasibility and acceptability of implementing a test to enable approach as part of Englands tracing strategy. MethodsContacts of confirmed COVID-19 cases were offered serial testing as an alternative to self-isolation using daily self-performed lateral flow device (LFD) tests for the first 7 days post exposure. Asymptomatic participants with a negative LFD result were given 24 hours of freedom from self-isolation between each test. A self-collected confirmatory PCR test was performed on testing positive or at the end of the LFD testing period. ResultsOf 1,760 contacts, 882 consented to daily testing, with 812 within 48 hours of exposure sent testing packs. Of those who declined to participate, 39.1% stated they had already accessed PCR testing. Of the 812 who were sent packs, 570 (70.2%) reported one or more LFD results; 102 (17.9%) tested positive. Concordance between reported LFD result and a supplied LFD image was 97.1%. 82.8% of PCR positive samples and 99.6% of PCR negative samples were correctly detected by LFD. The proportion of secondary cases from contacts of those who participated in the study and tested positive (6.3%; 95% CI: 3.4-11.1%) were comparable to a comparator group who self-isolated (7.6%; 95% CI: 7.3-7.8%). ConclusionThis study shows a high acceptability, compliance and positivity rates when using self-administered LFDs among contacts of confirmed COVID-19 cases. Offering routine testing as a structured part of the contact tracing process is likely to be an effective method of case ascertainment.

11.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21253500

RESUMEN

BackgroundIn December 2020, Public Health England with NHS Test and Trace initiated a pilot study in which close contacts of people with confirmed COVID-19 were given the option to carryout lateral flow device antigen tests at home, as an alternative to self-isolation for 10-14 days. In this study, we evaluated acceptability of and engagement with daily testing, and assessed levels of adherence to the rules relating to behaviour following positive or negative test results. MethodsWe conducted a service evaluation of a pilot study, involving an online cross-sectional survey offered to adult (> 18 years) contacts of confirmed COVID-19 cases who were invited to participate in seven days of daily testing instead of isolation. We used a comparison group of contacts who were not offered testing and performed self-isolation. Herein, we examine survey responses from a subset of those who took part in the pilot study and who responded to the evaluation questionnaire. ResultsAcceptability of daily testing was lower among survey respondents who were not offered the option of having it and among people from ethnic minority groups. Overall, 52% of respondents reported being more likely to share details of people that they had been in contact with following a positive test result, if they knew that their contacts would be offered the option of daily testing. Only 2% reported that they would be less likely to provide details of their contacts. On the days that they were trying to self-isolate, 19% of participants reported that they left the house, with no significant demographic group differences. Following a negative test, 13% of respondents reported that they increased their contacts, but most (58%) reported having fewer risky contacts. ConclusionsOur data suggest that daily testing is potentially acceptable, and may facilitate sharing contact details of close contacts among those who test positive for COVID-19, and promote adherence to self-isolation. A better understanding is needed of how to make this option more acceptable for all households. The impact of receiving a negative test on behaviour remains a risk that needs to be monitored and mitigated by appropriate messaging. Future research should examine attitudes and behaviour in a context where infection levels are lower, testing is more familiar, much of the population has been vaccinated and restrictions on activity have been reduced.

12.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21251735

RESUMEN

ObjectivesTo understand the experiences of those who underwent supported isolation as part of the response to the COVID-19 pandemic, after returning to the UK from Wuhan, China. DesignWe used semi-structured interviews to capture participants experiences and perceptions of supported isolation. SettingTelephone interviews carried out within approximately one month of an individual leaving supported isolation. Participants26 people who underwent supported isolation at either Arrowe Park Hospital (n = 18) or Kents Hill Park Conference Centre (n = 8) after being repatriated from Wuhan in January - February 2020. ResultsParticipants were willing to undergo supported isolation because they understood that it would protect themselves and others. Positive treatment by staff was fundamental to participants willingness to comply with isolation procedures. Despite the high level of compliance, participants expressed some uncertainty about what the process would involve. ConclusionsAs hotel quarantine is introduced across the UK for international arrivals, our findings suggest that those in charge should: communicate effectively before, during and after quarantine, emphasising why quarantine is important and how it will protect others; avoid enforcement and focus on supporting and promoting voluntary compliance; facilitate shared social experiences for those in quarantine; and ensure all necessary supplies are provided. Doing so will increase adherence and reduce any negative effects on wellbeing.

13.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21250777

RESUMEN

BackgroundSARS-CoV-2 antibody tests are used for population surveillance and might have a future role in individual risk assessment. Lateral flow immunoassays (LFIAs) can deliver results rapidly and at scale, but have widely varying accuracy. MethodsIn a laboratory setting, we performed head-to-head comparisons of four LFIAs: the Rapid Test Consortiums AbC-19 Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test. We analysed blood samples from 2,847 key workers and 1,995 pre-pandemic blood donors with all four devices. FindingsWe observed a clear trade-off between sensitivity and specificity: the IgG band of the SureScreen device and the AbC-19 device had higher specificities but OrientGene and Biomerica higher sensitivities. Based on analysis of pre-pandemic samples, SureScreen IgG band had the highest specificity (98.9%, 95% confidence interval 98.3 to 99.3%), which translated to the highest positive predictive value across any pre-test probability: for example, 95.1% (95%CI 92.6, 96.8%) at 20% pre-test probability. All four devices showed higher sensitivity at higher antibody concentrations ("spectrum effects"), but the extent of this varied by device. InterpretationThe estimates of sensitivity and specificity can be used to adjust for test error rates when using these devices to estimate the prevalence of antibody. If tests were used to determine whether an individual has SARS-CoV-2 antibodies, in an example scenario in which 20% of individuals have antibodies we estimate around 5% of positive results on the most specific device would be false positives. FundingPublic Health England. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched for evidence on the accuracy of the four devices compared in this study: OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, Biomerica COVID-19 IgG/IgM Rapid Test and the UK Rapid Test Consortiums AbC-19 Rapid Test. We searched Ovid MEDLINE (In-Process & Other Non-Indexed Citations and Daily), PubMed, MedRxiv/BioRxiv and Google Scholar from January 2020 to 16th January 2021. Search terms included device names AND ((SARS-CoV-2) OR (covid)). Of 303 records assessed, data were extracted from 24 studies: 18 reporting on the accuracy of the OrientGene device, 7 SureScreen, 2 AbC-19 and 1 Biomerica. Only three studies compared the accuracy of two or more of the four devices. With the exception of our previous report on the accuracy of the AbC-19 device, which the current manuscript builds upon, sample size ranged from 7 to 684. For details, see Supplementary Materials. The largest study compared OrientGene, SureScreen and Biomerica. SureScreen was estimated to have the highest specificity (99.8%, 95% CI 98.9 to 100%) and OrientGene the highest sensitivity (92.6%), but with uncertainty about the latter result due to small sample sizes. The other two comparative studies were small (n = 65, n = 67) and therefore provide very uncertain results. We previously observed spectrum effects for the AbC-19 device, such that sensitivity is upwardly biased if estimated only from PCR-confirmed cases. The vast majority of previous studies estimated sensitivity in this way. Added value of this studyWe performed a large scale (n = 4,842), head-to-head laboratory-based evaluation and comparison of four lateral flow devices, which were selected for evaluation by the UK Department of Health and Social Cares New Tests Advisory Group, on the basis of a survey of test and performance data available. We evaluated the performance of diagnosis based on both IgG and IgM bands, and the IgG band alone. We found a clear trade-off between sensitivity and specificity across devices, with the SureScreen and AbC-19 devices being more specific and OrientGene and Biomerica more sensitive. Based on analysis of 1,995 pre-pandemic blood samples, we are 99% confident that SureScreen (IgG band reading) has the highest specificity of the four devices (98.9%, 95% CI 98.3, 99.3%). We found evidence that all four devices have reduced sensitivity at lower antibody indices, i.e. spectrum effects. However, the extent of this varies by device and appears to be less for other devices than for AbC-19. Our estimates of sensitivity and specificity are likely to be higher than would be observed in real use of these devices, as they were based on majority readings of three trained laboratory personnel. Implications of all the available evidenceWhen used in epidemiological studies of antibody prevalence, the estimates of sensitivity and specificity provided in this study can be used to adjust for test errors. Increased precision in error rates will translate to increased precision in seroprevalence estimates. If lateral flow devices were used for individual risk assessment, devices with maximum specificity would be preferable. However, if, for an example, 20% of the tested population had antibodies, we estimate that around 1 in 20 positive results on the most specific device would be incorrect.

14.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20248161

RESUMEN

BackgroundThe evidence on risk factors for transmission of SARS-CoV-2 in community settings is sparse, yet this information is key to inform public health action. We investigated factors associated with being a COVID-19 case using data collected through contact tracing. MethodsWe conducted three retrospective, frequency-matched case-control studies between August 2020 and October 2020 using case data from the NHS Test and Trace programme. Controls were obtained through Market Research Panels. Multivariable analyses provided adjusted odds ratios (aORs) for multiple community exposure settings. We analysed the results in meta-analyses using random effects models to obtain pooled odds ratios (pORs). ResultsAcross all study periods, there was strong statistical evidence that working in healthcare (pOR 2.87, aOR range 2.72-3.08), social care (pOR 4.15, aOR range 2.46-5.41) or hospitality (pOR 2.36, aOR range 2.01-2.63) were associated with increased odds of being a COVID-19 case. There was also evidence that working in warehouse setting was associated with increased odds (pOR 3.86, aOR range 1.06-14.19), with a substantial increase in odds observed over the study periods. A similar pattern was also observed in education and construction. ConclusionsThe studies indicate that some workplace settings are associated with increased odds of being a case. However, it is not possible to determine how much of the transmission of SARS-CoV-2 took place within the workplace, and how much was associated with social, household or transport exposures.

15.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20247528

RESUMEN

In an effort to reduce the spread of COVID-19, the UK government has introduced a series of mitigation measures. The success of these measures in preventing transmission is dependent on adherence, which is currently considered to be low. Evidence highlights the disproportionate impact of mitigation measures on individuals from Black, Asian and minority ethnic (BAME) communities, as well as among those on a low income, and an understanding of barriers to adherence in these populations is needed. In this qualitative study we examined patterns of adherence to mitigation measures and reasons underpinning these behaviors among people on low income and those from BAME communities. Semi-structured interviews were conducted with 20 participants from BAME and low-income White backgrounds. The topic guide was designed to explore how individuals are adhering to social distancing and self-isolation measures during the COVID-19 pandemic, and to explore in detail the reasons underpinning this behavior. Data were analyzed using thematic analysis following which charts were used to help compare concepts within and between participants and develop an understanding of patterns of adherence. Participants were confused by the constantly changing and seemingly contradictory rules and guidance. As a result, decisions were made about how best to protect themselves and their household from COVID-19, and from the detrimental impact of lockdown restrictions. This was not always in line with government advice. We identified three categories of adherence to lockdown measures 1) caution motivated super-adherence 2) risk-adapted partial-adherence and 3) necessity-driven partial-adherence. Decisions about adherence considered potential for exposure to the virus, ability to reduce risk through use of protective measures, and perceived importance of/need for the behavior. This research highlights a need for a more nuanced understanding of adherence to lockdown measures. Provision of practical and financial support could reduce the number of people who have to engage in necessity-driven partial-adherence. Information about viral transmission could help people assess the risk associated with partial-adherence more accurately. More evidence is required on population level risks of people adopting risk-adapted partial-adherence.

16.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20222778

RESUMEN

Immune correlates of protection from COVID-19 are incompletely understood. 2,826 keyworkers had T-SPOT(R) Discovery SARS-CoV-2 tests (measuring interferon-{gamma} secreting, SARS-CoV-2 responsive T cells, Oxford Immunotec Ltd), and anti-Spike S1 domain IgG antibody levels (EuroImmun AG) performed on recruitment into a cohort study. 285/2,826 (10.1%) of participants had positive SARS-CoV-2 RT-PCR tests, predominantly associated with symptomatic illness, during 200 days followup. T cell responses to Spike, Nucleoprotein and Matrix proteins (SNM responses) were detected in some participants at recruitment, as were anti-Spike S1 IgG antibodies; higher levels of both were associated with protection from subsequent SARS-CoV-2 test positivity. In volunteers with moderate antibody responses, who represented 39% (252/654) of those with detectable anti-Spike IgG, protection was partial, and higher with higher circulating T cell SNM responses. SARS-CoV-2 responsive T cell numbers predict protection in individuals with low anti-Spike IgG responses; serology alone underestimates the proportion of the population protected after infection.

17.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20195628

RESUMEN

Introduction In the containment phase of the response to the COVID-19 outbreak, Public Health England (PHE) delivered advice to travellers arriving at major UK ports. We aimed to rapidly evaluate the impact and effectiveness of these communication materials for passengers in the early stages of the pandemic. Methods In stage I (Patient and Public Involvement, PPI) we interviewed seven travellers who had returned from China in January and February 2020. We used these results to develop a questionnaire and topic guides for stage II, a cross-sectional survey and follow-up interviews with passengers arriving at London Heathrow Airport on scheduled flights from China and Singapore. The survey assessed passengers' knowledge of symptoms, actions to take and attitudes towards PHE COVID-19 public health information; interviews explored their views of official public health information and self-isolation. Results In stage II, 121 passengers participated in the survey and 15 in follow-up interviews. 83% of surveyed passengers correctly identified all three COVID-19 associated symptoms listed in PHE information at that time. Most could identify the recommended actions and found the advice understandable and trustworthy. Interviews revealed that passengers shared concerns about the lack of wider official action, and that passengers' knowledge had been acquired elsewhere as much from PHE. Respondents also noted their own agency in choosing to self-isolate, partially as a self-protective measure. Conclusion PHE COVID-19 public health information was perceived as clear and acceptable, but we found that passengers acquired knowledge from various sources and they saw the provision of information alone on arrival as an insufficient official response. Our study provides fresh insights into the importance of taking greater account of diverse information sources and of the need for public assurance in creating public health information materials to address global health threats. Keywords COVID-19, public health advice, government, policy, airport, international travel

18.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20178186

RESUMEN

ObjectiveTo measure the association between self-reported signs and symptoms and SARS-CoV-2 seropositivity. DesignCross-sectional study of three key worker groups. SettingSix acute NHS hospitals and two Police and Fire and Rescue sites in England. ParticipantsIndividuals were recruited from three streams: (A) Police and Fire and Rescue services (n = 1147), (B) healthcare workers (n = 1546) and (C) healthcare workers with previously positive virus detection (n = 154). Main outcome measuresDetection of anti-SARS-CoV-2 antibodies in plasma. Results943 of the 2847 participants (33%) reported belief they had had COVID-19, having experienced compatible symptoms (including 152 from Stream C). Among individuals reporting COVID-19 compatible symptoms, 466 (49%) were seronegative on both Nucleoprotein (Roche) and Spike-protein (EUROIMMUN) antibody assays. However, among the 268 individuals with prior positive SARS-CoV-2 tests, of whom 96% reported symptoms with onset a median of 63 days (IQR 52 - 75 days) prior to venesection, Roche and EUROIMMUN assays had 96.6% (95% CI 93.7% - 98.2%) and 93.3% (95% CI 89.6% - 95.7%) sensitivity respectively. Symptomatic but seronegative individuals had significantly earlier symptom onset dates than the symptomatic seropositive individuals, shorter illness duration and a much lower anosmia reporting frequency. ConclusionsSelf-reported belief of COVID-19 was common among our frontline worker cohort. About half of these individuals were seronegative, despite a high sensitivity of serology in this cohort, at least in individuals with previous positive PCR results. This is compatible with non-COVID-19 respiratory disease during the COVID-19 outbreak having been commonly mistaken for COVID-19 within the key worker cohort studied. What is already known on this topicScreening for SARS-CoV-2 antibodies is under way in some key worker groups; however, how this adds to self-reported COVID-19 illness is unclear. There are limited studies that investigate the association between self-reported belief of COVID-19 illness and seropositivity. What this study addsAbout one third of a large cohort of key frontline workers believed they had had COVID-19 infection. In around half of these there was no serological evidence of infection. Individuals who believed they had previous infection, but were seronegative, differed systematically from the seropositive individuals: disordered sense of taste and smell was less common, illness duration was shorter, and reported onset of illness commonly predated the main COVID-19 epidemic in the UK. Although some individuals with previous COVID-19 may be seronegative, among symptomatic individuals who had PCR-confirmed SARS-CoV-2 within our cohort, sensitivity of the two immunoassays used (Roche Elecsys (R) and EUROIMMUN) exceeded 90%. Together, these data indicate that many key workers may falsely believe, based on symptomatic illness experienced during 2020, that they have had COVID-19. Further research investigating the relationship between antibody detection and protection from future infection, with and without a history of COVID-19 disease, will help define the role serological testing can play in clinical practice.

19.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20119040

RESUMEN

ObjectivesTo investigate factors associated with adherence to self-isolation and lockdown measures due to COVID-19 in the UK. DesignOnline cross-sectional survey. SettingData were collected between 6th and 7th May 2020. Participants2240 participants living in the UK aged 18 years or over. Participants were recruited from YouGovs online research panel. Main outcome measuresHaving gone out in the last 24 hours in those who reported symptoms of COVID-19 in their household. Having gone out shopping for items other than groceries, toiletries or medicines (non-essentials), and total number of outings, in the last week in those who reported no symptoms of COVID-19 in their household. Results217 people (9.7%) reported that they or someone in their household had symptoms of COVID-19 (cough or high temperature / fever) in the last seven days. Of these people, 75.1% had left the home in the last 24 hours (defined as non-adherent). Factors associated with non-adherence were being male, less worried about COVID-19, and perceiving a smaller risk of catching COVID-19. Adherence was associated with having received help from someone outside your household. Results should be taken with caution as there was no evidence for associations when controlling for multiple analyses. Of people reporting no symptoms in the household, 24.5% had gone out shopping for non-essentials in the last week (defined as non-adherent). Factors associated with non-adherence and with a higher total number of outings in the last week included decreased perceived effectiveness of Government "lockdown" measures, decreased perceived severity of COVID-19, and decreased estimates of how many other people were following lockdown rules. Having received help was associated with better adherence. ConclusionsAdherence to self-isolation is poor. As we move into a new phase of contact tracing and self-isolation, it is essential that adherence is improved. Communications should aim to increase knowledge about actions to take when symptomatic or if you have been in contact with a possible COVID-19 case. They should also emphasise the risk of catching and spreading COVID-19 when out and about and the effectiveness of preventative measures. Using volunteer networks effectively to support people in isolation may promote adherence. WHAT IS ALREADY KNOWN ON THIS TOPICO_LIThe UK Government introduced "lockdown" measures, including physical or social distancing, on 23rd March 2020 due to COVID-19. C_LIO_LIGovernment guidance states that people with symptoms of COVID-19 should not leave their home, also known as self-isolation. C_LIO_LIThere is no research investigating adherence to self-isolation and lockdown measures, or factors associated with self-isolation or lockdown measures in the UK. C_LI WHAT THIS STUDY ADDSO_LIApproximately 10% of participants indicated that they had had symptoms of potential COVID-19 (cough and high temperature / fever) in the last week. Of these participants, 75% had left their home in the last 24 hours. C_LIO_LIFactors associated with non-adherence to self-isolation measures included being male, less worried about COVID-19, and perceiving a smaller risk of catching COVID-19. However, these results should be taken with caution as there was no longer evidence for associations when correcting for multiple analyses. C_LIO_LI25% of people who reported no symptoms in their household reported having gone out shopping for items other than groceries, toiletries or medicines in the last week; this was not allowed by Government guidelines in place at the time of data collection. C_LIO_LIFactors associated with non-adherence to lockdown measures, and increased number of outings in the last week, included decreased perceived effectiveness of Government "lockdown" measures, decreased perceived severity of COVID-19, and decreased estimates of how many other people were following lockdown rules. C_LI

20.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20137901

RESUMEN

BackgroundTo investigate factors associated with anxiety, depression, and self-reported general health during "lockdown" due to COVID-19 in the UK. MethodsOnline cross-sectional survey of a nationally-representative sample of 2240 participants living in the UK aged 18 years or over (data collected 6-7 May 2020). Participants were recruited from YouGovs online research panel. OutcomesIn this sample, 21{middle dot}9% (n=458, 95% CI [20{middle dot}1% to 23{middle dot}7%]) reported probable anxiety (scored three or over on the GAD-2); while 23{middle dot}5% (n=494, 95% CI [21{middle dot}7% to 25{middle dot}3]) reported probable depression (scored three or over on the PHQ-2). Poorer mental health was associated with greater financial hardship during the lockdown, thinking that you would lose contact with friends or family if you followed Government measures, more conflict with household members during the lockdown, less sense of community with people in your neighbourhood, and lower perceived effectiveness of Government measures. Females and those who were younger were likely to report higher levels of anxiety and depression. The majority of participants reported their general health as "good" (as measured by the first item of the SF-36). Poorer self-reported general health was associated with psychological distress, greater worry about COVID-19 and markers of inequality. InterpretationRates of self-reported anxiety and depression in the UK during the lockdown were greater than population norms. Reducing financial hardship, promoting social connectedness, and increasing solidarity with neighbours and household members may help ease rifts within the community which are associated with distress, thereby improving mental health. Reducing inequality may also improve general health. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSO_LIQuarantine is associated with adverse psychological outcomes. C_LIO_LIPsychological distress during quarantine is associated with greater financial loss, greater perceived susceptibility to and severity of the illness, and greater frustration and boredom during quarantine. C_LIO_LIMeasures put in place to prevent the spread of COVID-19 have highlighted existing inequalities in society, disproportionally affecting younger people, those in lower-income households, and Black and minority ethnic groups. C_LIO_LIResearch in the UK and other countries indicates that rates of anxiety and depression during restrictions of movement such as "lockdown" measures are higher than population norms. C_LI Added value of this studyO_LIIn this study, 22% of the sample reported anxiety, while 24% reported depression. Normative data indicate that these rates are usually approximately 5% and 7% respectively. C_LIO_LIFactors associated with psychological distress included greater financial hardship, poorer social connectedness, greater conflict within the household and the wider neighbourhood, being female and of younger age. C_LIO_LISelf-reported general health in the sample was "good" on average. Factors associated with poorer self-reported general health included markers of inequality and greater worry about COVID-19. C_LI Implications of all the available evidenceO_LIDecreasing the financial impact of measures put in place to prevent the spread of COVID-19 may help improve mental health. C_LIO_LIInterventions promoting social connectedness in isolated young people and measures that increase household and neighbourhood solidarity may help improve mental health. C_LI

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