Association of results of four lateral flow antibody tests with subsequent SARS-CoV-2 infection

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.

A mixed methods analysis of participation in social contact surveys

BackgroundSocial contact survey data forms a core component of modern epidemic models: however, there has been little assessment of the potential biases in such data. MethodsWe conducted focus groups with university students who had (n=13) and had not (n=14) completed a social contact survey during the COVID-19 pandemic. Qualitative findings were explored quantitatively by analysing participation data. ResultsThe opportunity to contribute to COVID-19 research, to be heard and feel useful were frequently reported motivators for participating in the contact survey. Reductions in survey engagement following lifting of COVID-19 restrictions may have occurred because the research was perceived to be less critical and/ or because the participants were busier and had more contacts. Having a high number of contacts to report, uncertainty around how to report each contact, and concerns around confidentiality were identified as factors leading to inaccurate reporting. Focus groups participants thought that financial incentives or provision of study results would encourage participation. ConclusionsIncentives could improve engagement with social contact surveys. Qualitative research can inform the format, timing, and wording of surveys to optimise completion and accuracy. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/22270006v2_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@10a3dd4org.highwire.dtl.DTLVardef@1616032org.highwire.dtl.DTLVardef@1f2aab8org.highwire.dtl.DTLVardef@a62043_HPS_FORMAT_FIGEXP M_FIG C_FIG

Impacts of vaccination and asymptomatic testing on SARS-CoV-2 transmission dynamics in a university setting

We investigate the impact of vaccination and asymptomatic testing uptake on SARS-CoV-2 transmission in a university student population using a stochastic compartmental model. We find that the magnitude and timing of outbreaks is highly variable depending on the transmissibility of the most dominant strain of SARS CoV-2 and under different vaccine uptake levels and efficacies. When delta is the dominant strain, low level interventions (no asymptomatic testing, 30% vaccinated with a vaccine that is 80% effective at reducing infection) lead to 53-71% of students become infected during the first term. Asymptomatic testing is most useful when vaccine uptake is low: when 30% of students are vaccinated, 90% uptake of asymptomatic testing leads to almost half the case numbers. With high interventions (90% using asymptomatic testing, 90% vaccinated) cumulative incidence is 7-9%, with around 80% of these cases estimated to be asymptomatic. However, under emergence of a new variant that is at least twice as transmissible as delta and with the vaccine efficacy against infection reduced to 55%, large outbreaks are likely in universities, even with very high (90%) uptake of vaccination and 100% uptake of asymptomatic testing. If vaccine efficacy against infection against this new variant is higher (70%), then outbreaks can be mitigated if there is least 50% uptake of asymptomatic testing additional to 90% uptake of vaccination. Our findings suggest that effective vaccination is critical for controlling SARS-CoV-2 transmission in university settings with asymptomatic testing ranging from additionally useful to critical, depending on effectiveness and uptake of vaccination. Other measures may be necessary to control outbreaks under the emergence of a more transmissible variant with vaccine escape.

Limited impact of contact tracing in a University setting for COVID-19 due to asymptomatic transmission and social distancing

Contact tracing is an important tool for controlling the spread of infectious diseases, including COVID-19. Here, we investigate the spread of COVID-19 and the effectiveness of contact tracing in a university population, using a data-driven ego-centric network model constructed with social contact data collected during 2020 and similar data collected in 2010. We find that during 2020, university staff and students consistently reported fewer social contacts than in 2010, however those contacts occurred more frequently and were of longer duration. We find that contact tracing in the presence of social distancing is less impactful than without social distancing. By combining multiple data sources, we show that University-aged populations are likely to develop asymptomatic COVID-19 infections. We find that asymptomatic index cases cannot be reliably back-traced through contact tracing and consequently transmission in their social network is not significantly reduced through contact tracing. In summary, social distancing restrictions had a large impact on limiting COVID-19 outbreaks in universities; to reduce transmission further contact tracing should be used in conjunction with alternative interventions.

Epidemiology and transmission of COVID-19 in cases and close contacts in Georgia in the first four months of the epidemic

BackgroundBetween February and June 2020, 917 COVID-19 cases and 14 COVID-19-related deaths were reported in Georgia. Early on, Georgia implemented non-pharmaceutical interventions (NPI) including extensive contact tracing and restrictions on movement. AimTo characterize the demographics of those tested and infected with COVID-19 in Georgia; to evaluate factors associated with transmission between cases and their contacts; and to determine how transmission varied due to NPI up to 24 June 2020. MethodsWe use data gathered by the Georgian National Center for Disease Control on all polymerase chain reaction tests conducted (among symptomatic patients, through routine testing and contact tracing); hospitalization data for confirmed cases, and contact tracing data. We calculated the number of contacts per index case, the secondary attack rate (% contacts infected), and effective R number (new cases per index case), and used logistic regression to estimate how age, gender, and contact type affected transmission. ResultsMost contacts and transmission events were between family members. Contacts <40 years were less likely to be infected, while infected individuals >50 were more likely to die than younger patients. Contact tracing identified 917 index cases with mean 3.1 contacts tested per case, primarily family members. The overall secondary attack rate was 28% (95% confidence interval [CI]: 26-29%) and effective R number was 0.87 (95%CI 0.81-0.93), peaking at 1.1 (95%CI 0.98-1.2) during the period with strongest restrictions. ConclusionGeorgia effectively controlled the COVID-19 epidemic in its early stages, although evidence does not suggest transmission was reduced during the strict lockdown period. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and MedRxiv for papers reporting research using contact tracing data to evaluate the characteristics of the COVID-19 epidemic in any country. A number of analyses were identified from Asia, including China, Taiwan, Maldives, Thailand, South Korea, and India, but none from other regions other than one previous analysis conducted in Europe, focusing on the first two months of the COVID-19 epidemic in Cyprus. Studies evaluated number of contacts and different contact types, secondary attack rate, and effective R number. However, none of these studies compared characteristics between different time periods or under varied levels of non-pharmaceutical interventions or restrictions on social mixing. Added value of this studyIn this study, we use contact tracing data from Georgia from all cases identified in the first four months of the epidemic, as well as testing and hospitalization data, to evaluate the number and type of contacts, effective R number (new cases per index case), and secondary attack rate (proportion of contacts infected) in this population, and whether these measures changed before, during, and after the lockdown period. We also evaluated how the chance of transmission varied by type of index case and contact. Our results indicate that number of contacts remained relatively low throughout the study period, so although the secondary attack rate was relatively high (28%) compared to that seen in studies in Asia (10-15%), the effective R number was less than one overall, peaking at 1.1 (0.98-1.2) during the strictest lockdown period, with easing of restrictions corresponding to a lower effective R of 0.87 (0.77-0.97). Most transmission occurred between family members with transmission very low between co-workers, friends, neighbours, and medical personnel, indicating that the restrictions on social mixing were effective at keeping the epidemic under control during this period. Implications of all the available evidenceOur study presents the first analysis of the successful control of a COVID-19 epidemic in a European country, indicating that despite a high secondary attack rate, reduction in contacts outside the home, and a well-timed lockdown, were able to keep transmission under control.

Limits of lockdown: characterising essential contacts during strict physical distancing

COVID-19 has exposed health inequalities within countries and globally. The fundamental determining factor behind an individuals risk of infection is the number of social contacts they make. In many countries, physical distancing measures have been implemented to control transmission of SARS-CoV-2, reducing social contacts to a minimum. Characterising unavoidable social contacts is key for understanding the inequalities behind differential risks and planning vaccination programmes. We utilised an existing English longitudinal birth cohort, which is broadly representative of the wider population (n=6807), to explore social contact patterns and behaviours when strict physical distancing measures were in place during the UKs first lockdown in March-May 2020. Essential workers, specifically those in healthcare, had 4.5 times as many contacts as non-essential workers [incident rate ratio = 4.42 (CI95%: 3.88-5.04)], whilst essential workers in other sectors, mainly teaching and the police force had three times as many contacts [IRR = 2.84 (2.58-3.13)]. The number of individuals in a household, which is conflated by number of children, increases essential social contacts by 40%. Self-isolation effectively reduces numbers of contacts outside of the home, but not entirely. Together, these findings will aid the interpretation of epidemiological data and impact the design of effective SARS-CoV-2 control strategies, such as vaccination, testing and contact tracing.

Contact patterns before and during the UK's Autumn 2020 COVID-19 lockdown among university students and staff

IntroductionUK universities re-opened in September 2020, despite the on-going coronavirus epidemic. During the first term, various national social distancing measures were introduced, including banning groups of >6 people and the second lockdown in November. COVID-19 can spread rapidly in university-settings, and students adherence to social distancing measures is critical for controlling transmission. MethodsWe measured university staff and student contact patterns via an online, longitudinal survey capturing self-reported contacts on the previous day. We investigated the change in contacts associated with COVID-19 guidance periods: post-first lockdown (23/06/2020-03/07/2020), relaxed guidance period (04/07/2020-13/09/2020), "rule-of-six" period (14/09/2020-04/11/2020), and the second lockdown (05/11/2020-25/11/2020). Results722 staff (4199 responses) (mean household size: 2.6) and 738 students (1906 responses) (mean household size: 4.5) were included in the study. Contact number decreased with age. Staff in single-person households reported fewer contacts than individuals in 2-and 3-person households, and individuals in 4-and 5-person households reported more contacts. For staff, daily contacts were higher in the relaxed guidance and "rule-of-six" periods (means: 3.2 and 3.5, respectively; medians: 3) than the post-first lockdown and second lockdown periods (means: 4.5 and 5.4, respectively; medians: 2). Few students responded until 05/10/2020, after which the median student contacts was 2 and the mean was 5.7, until the second lockdown when it dropped to 3.1. DiscussionUniversity staff and students responded to national guidance by altering their social contacts. The response in staff and students was similar, suggesting that students are able to adhere to social distancing guidance while at university.

Modelling pooling strategies for SARS-CoV-2 testing in a university setting

Pre-symptomatic and asymptomatic transmission of SARS-CoV-2 are important elements in the Covid-19 pandemic, and until vaccines are made widely available there remains a reliance on testing to manage the spread of the disease, alongside non-pharmaceutical interventions such as measures to reduce close social interactions. In the UK, many universities opened for blended learning for the 2020-2021 academic year, with a mixture of face to face and online teaching. In this study we present a simulation framework to evaluate the effectiveness of different asymptomatic testing strategies within a university setting, across a range of transmission scenarios. We show that when positive cases are clustered by known social structures, such as student households, the pooling of samples by these social structures can substantially reduce the total cost of conducting RT-qPCR tests. We also note that routine recording of quantitative RT-qPCR results would facilitate future modelling studies.

Contacts and behaviours of university students during the COVID-19 pandemic at the start of the 2020/21 academic year

CONQUEST (COroNavirus QUESTionnaire) is an online survey of contacts, behaviour, and COVID-19 symptoms for University of Bristol (UoB) staff/students. We analysed survey results from the start of the 2020/2021 academic year, prior to the second national lockdown (14/09/2020-01/11/2020), where COVID-19 outbreaks led to lockdown of some student halls of residence. The aim of these analyses was to enhance knowledge of student contact patterns to inform infection disease mathematical modelling approaches. Responses captured information on demographics, contacts on the previous day, symptoms and self-isolation during the prior week, and COVID-19 status. 740 students provided 1261 unique records. Of 42 (3%) students testing positive in the prior fortnight, 99% had been self-isolating. The median number of contacts on the previous day was 2 (interquartile range: 1-5), mode: 1, mean: 6.1; 8% had [≥]20 contacts. 57% of student contacts were other UoB students/staff. Most students reported few daily contacts but there was heterogeneity, and some reported many. Around 40% of student contacts were with individuals not affiliated with UoB, indicating potential for transmission to non-students/staff.

High COVID-19 transmission potential associated with re-opening universities can be mitigated with layered interventions

Background: Re-opening universities while controlling COVID-19 transmission poses unique challenges. UK universities typically host 20,000 to 40,000 undergraduate students, with the majority moving away from home to attend. In the absence of realistic mixing patterns, previous models suggest that outbreaks associated with universities re-opening are an eventuality. Methods: We developed a stochastic transmission model based on realistic mixing patterns between students. We evaluated alternative mitigation interventions for a representative university. Results: Our model predicts, for a set of plausible parameter values, that if asymptomatic cases are half as infectious as symptomatic cases then 5,760 (3,940 - 7,430) out of 28,000 students, 20% (14% - 26%), could be infected during the first term, with 950 (656 - 1,209) cases infectious on the last day of term. If asymptomatic cases are as infectious as symptomatic cases then three times as many cases could occur, with 94% (93% - 94%) of the student population getting infected during the first term. We predict that one third of infected students are likely to be in their first year, and first year students are the main drivers of transmission due to high numbers of contacts in communal residences. We find that reducing face-to-face teaching is likely to be the single most effective intervention, and this conclusion is robust to varying assumptions about asymptomatic transmission. Supplementing reduced face-to-face testing with COVID-secure interactions and reduced living circles could reduce the percentage of infected students by 75%. Mass testing of students would need to occur at least fortnightly, is not the most effective option considered, and comes at a cost of high numbers of students requiring self-isolation. When transmission is controlled in the student population, limiting imported infection from the community is important. Conclusions: Priority should be given to understanding the role of asymptomatic transmission in the spread of COVID-19. Irrespective of assumptions about asymptomatic transmission, our findings suggest that additional outbreak control measures should be considered for the university setting. These might include reduced face-to-face teaching, management of student mixing and enhanced testing. Onward transmission to family members at the end of term is likely without interventions.

COVID-19 transmission in a university setting: a rapid review of modelling studies

Managing COVID-19 within a university setting presents unique challenges. At the start of term, students arrive from geographically diverse locations and potentially have higher numbers of social contacts than the general population, particularly if living in university halls of residence accommodation. Mathematical models are useful tools for understanding the potential spread of infection and are being actively used to inform policy about the management of COVID-19. Our aim was to provide a rapid review and appraisal of the literature on mathematical models investigating COVID-19 infection in a university setting. We searched PubMed, Web of Science, bioRxiv/ medRxiv and sought expert input via social media to identify relevant papers. BioRxiv/ medRxiv and PubMed/Web of Science searches took place on 3 and 6 July 2020, respectively. Papers were restricted to English language. Screening of peer-reviewed and pre-print papers and contact with experts yielded five relevant papers - all of which were pre-prints. All models suggest a significant potential for transmission of COVID-19 in universities. Testing of symptomatic persons and screening of the university community regardless of symptoms, combined with isolation of infected individuals and effective contact tracing were critical for infection control in the absence of other mitigation interventions. When other mitigation interventions were considered (such as moving teaching online, social/physical distancing, and the use of face coverings) the additional value of screening for infection control was limited. Multiple interventions will be needed to control infection spread within the university setting and the interaction with the wider community is an important consideration. Isolation of identified cases and quarantine of contacts is likely to lead to large numbers of students requiring educational, psychological and behavioural support and will likely have a large impact on the attendance of students (and staff), necessitating online options for teaching, even where in-person classes are taking place. Models were highly sensitive to assumptions in the parameters, including the number and type of individuals contacts, number of contacts traced, frequency of screening and delays in testing. Future models could aid policy decisions by considering the incremental benefit of multiple interventions and using empirical data on mixing within the university community and with the wider community where available. Universities will need to be able to adapt quickly to the evolving situation locally to support the health and wellbeing of the university and wider communities.