How to design and implement a university-based COVID-19 testing programme? An evaluation of a novel RT-LAMP COVID-19 testing programme in a UK university.

BACKGROUND: Little is known about how asymptomatic testing as a method to control transmission of COVID-19 can be implemented, and the prevalence of asymptomatic infection within university populations. The objective of this study was to investigate how to effectively set-up and implement a COVID-19 testing programme using novel reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) technology and to quantify the scale of asymptomatic infection on a university campus. METHODS: An observational study to describe the set-up and implementation of a novel COVID-19 testing programme on a UK university campus between September and December 2020. RT-LAMP testing was used to identify asymptomatic cases. RESULTS: A total of 1,673 tests were performed using RT-LAMP during the study period, of which 9 were positive for COVID-19, giving an overall positivity rate of 0.54%, equivalent to a rate in the tested population of 538 cases per 100,000 over the duration of testing. All positive tests were found to be positive on RT-PCR testing, giving a false positive rate of 0%. CONCLUSIONS: This study shows that it is possible to rapidly setup a universal university testing programme for COVID-19 in collaboration with local healthcare providers using RT-LAMP testing. Positive results were comparable to those in the local population, though with a different peak of infection. Further research to inform the design of the testing programme includes focus groups of those who underwent testing and further interrogation of the demographics of those opting to be tested to identify potential access problems or inequalities.

A rapid RT-LAMP SARS-CoV-2 screening assay for collapsing asymptomatic COVID-19 transmission.

PURPOSE: To demonstrate the diagnostic performance of rapid SARS-CoV-2 RT-LAMP assays, comparing the performance of genomic versus sub-genomic sequence target with subsequent application in an asymptomatic screening population. METHODS: RT-LAMP diagnostic specificity (DSe) and sensitivity (DSe) was determined using 114 RT-PCR clinically positive and 88 RT-PCR clinically negative swab samples processed through the diagnostic RT-PCR service within the University Hospitals of Leicester NHS Trust. A swab-based RT-LAMP SARS-CoV-2 screening programme was subsequently made available to all staff and students at the University of Leicester (Autumn 2020), implemented to ISO 15189:2012 standards using NHS IT infrastructure and supported by University Hospital Leicester via confirmatory NHS diagnostic laboratory testing of RT-LAMP 'positive' samples. RESULTS: Validation samples reporting a Ct < 20 were detected at 100% DSe and DSp, reducing to 95% DSe (100% DSp) for all samples reporting a Ct < 30 (both genomic dual sub-genomic assays). Advisory screening identified nine positive cases in 1680 symptom free individuals (equivalent to 540 cases per 100,000) with results reported back to participants and feed into national statistics within 48 hours. CONCLUSION: This work demonstrates the utility of a rapid RT-LAMP assay for collapsing transmission of SARS-CoV-2 in an asymptomatic screening population.

Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis.

OBJECTIVE: To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19. DESIGN: Two stage individual participant data meta-analysis. SETTING: Secondary and tertiary care. PARTICIPANTS: 46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021. DATA SOURCES: Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in The BMJ, and through PROSPERO, reference checking, and expert knowledge. MODEL SELECTION AND ELIGIBILITY CRITERIA: Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor. METHODS: Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters. MAIN OUTCOME MEASURES: 30 day mortality or in-hospital mortality. RESULTS: Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al's model (0.96, 0.59 to 1.55, 0.21 to 4.28). CONCLUSION: The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.

Predictors of adverse outcome in the first and second waves of the COVID-19 pandemic: results from a UK centre.

BACKGROUND/AIMS: Data concerning differences in demographics/disease severity between the first and second waves of COVID-19 are limited. We aimed to examine prognosis in patients presenting to hospital with COVID-19 amongst different ethnic groups between the first and second waves in the UK. METHODS: In this retrospective cohort study, we included 1763 patients presenting to a regional hospital centre in Leicester (UK) and compared those in the first (n = 956) and second (n = 807) waves. Admission National Early Warning Scores, mechanical ventilation and mortality rate were lower in the second wave compared with the first. RESULTS: Thirty-day mortality risk in second wave patients was approximately half that of first wave patients [adjusted hazard ratio (aHR) 0.55, 95% confidence interval (CI) 0.40-0.75]. In the second wave, Black patients were at higher risk of 30-day mortality than White patients (4.73, 1.56-14.3). CONCLUSION: We found that disporportionately higher risks of death in patients from ethnic minority groups were not equivalent across consecutive waves of the pandemic. This suggests that risk factors for death in those from ethnic minority groups are malleable and potentially reversible. Our findings need urgent investigation in larger studies.

Design and implementation of a university-based COVID-19 testing programme: an observational study

Background Little is known about how asymptomatic testing as a method to control the transmission of COVID-19 can be successfully implemented, and the prevalence of asymptomatic infection within university populations. The aim of this study was to describe the methodology of implementing a novel asymptomatic mass testing programme, and to report the number of positive cases diagnosed during the study period. To our knowledge, this study is the first to report prevalence of asymptomatic COVID-19 infection within a UK university population using reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) as a molecular diagnostic tool. Methods An observational study was undertaken to describe the set-up and implementation of a novel COVID-19 testing programme on a UK university campus between Sept 28 and Dec 18, 2020. Students and staff members volunteered for testing throughout the term. The programme used RT-LAMP testing to identify asymptomatic cases within the population. Any positive cases received RT-PCR testing to confirm the result using the current gold-standard testing methodology. Findings 1673 tests were done using RT-LAMP during the study period, of which nine were positive for COVID-19. This gave an overall positivity rate of 0·54%, equivalent to a rate in the tested population of 538 cases per 100 000 over the duration of testing. All positive tests were also found to be positive on RT-PCR testing, giving a false positive rate of 0%. Uptake was affected by changes to delivery of university teaching, leading to lower attendance on campus throughout the term. Interpretation This study shows that it is possible to rapidly set up a universal university testing programme for COVID-19 in collaboration with local health-care providers using RT-LAMP testing, with full concordance between RT-LAMP testing and RT-PCR testing on positive RT-LAMP results. Positive results were similar to those in the local population, although with a different weekly peak of infection. Funding None.

SARS-CoV-2 vaccine uptake in a multi-ethnic UK healthcare workforce: A cross-sectional study.

BACKGROUND: Healthcare workers (HCWs) and ethnic minority groups are at increased risk of COVID-19 infection and adverse outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is now available for frontline UK HCWs; however, demographic/occupational associations with vaccine uptake in this cohort are unknown. We sought to establish these associations in a large UK hospital workforce. METHODS AND FINDINGS: We conducted cross-sectional surveillance examining vaccine uptake amongst all staff at University Hospitals of Leicester NHS Trust. We examined proportions of vaccinated staff stratified by demographic factors, occupation, and previous COVID-19 test results (serology/PCR) and used logistic regression to identify predictors of vaccination status after adjustment for confounders. We included 19,044 HCWs; 12,278 (64.5%) had received SARS-CoV-2 vaccination. Compared to White HCWs (70.9% vaccinated), a significantly smaller proportion of ethnic minority HCWs were vaccinated (South Asian, 58.5%; Black, 36.8%; p < 0.001 for both). After adjustment for age, sex, ethnicity, deprivation, occupation, SARS-CoV-2 serology/PCR results, and COVID-19-related work absences, factors found to be negatively associated with vaccine uptake were younger age, female sex, increased deprivation, pregnancy, and belonging to any non-White ethnic group (Black: adjusted odds ratio [aOR] 0.30, 95% CI 0.26-0.34, p < 0.001; South Asian: aOR 0.67, 95% CI 0.62-0.72, p < 0.001). Those who had previously had confirmed COVID-19 (by PCR) were less likely to be vaccinated than those who had tested negative. Limitations include data being from a single centre, lack of data on staff vaccinated outside the hospital system, and that staff may have taken up vaccination following data extraction. CONCLUSIONS: Ethnic minority HCWs and those from more deprived areas as well as younger staff and female staff are less likely to take up SARS-CoV-2 vaccination. These findings have major implications for the delivery of SARS-CoV-2 vaccination programmes, in HCWs and the wider population, and should inform the national vaccination programme to prevent the disparities of the pandemic from widening.

No cases of asymptomatic SARS-CoV-2 infection among healthcare staff in a city under lockdown restrictions: lessons to inform 'Operation Moonshot'.

BACKGROUND: Leicester was the first city in the UK to have 'local lockdown' measures imposed in response to high community rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. As part of this response, a directive was issued by NHS England to offer testing of asymptomatic healthcare workers (HCWs) at University Hospitals of Leicester NHS Trust (UHL) for SARS-CoV-2 infection. METHODS: Between 20 July and 14 August 2020, we invited all HCWs at UHL to attend for SARS-CoV-2 testing by nucleic acid amplification (NAAT). We combined the result of this assay with demographic information from the electronic staff record. RESULTS: A total of 1150 staff (~8% of the workforce) volunteered. The median age was 46 years (IQR 34-55), 972 (84.5%) were female; 234 (20.4%) were of South Asian and 58 (5.0%) of Black ethnicity; 564 (49.0%) were nurses/healthcare assistants. We found no cases of asymptomatic infection. In comparison, average community test positivity rate in Leicester city was 2.6%. CONCLUSIONS: Within the context of local lockdowns due to high community transmission rates, voluntary testing of asymptomatic staff has low uptake and low yield and thus its premise and cost-effectiveness should be re-considered.

Demographic and occupational determinants of anti-SARS-CoV-2 IgG seropositivity in hospital staff.

BACKGROUND: Although evidence suggests that demographic characteristics including minority ethnicity increase the risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is unclear whether these characteristics, together with occupational factors, influence anti-SARS-CoV-2 IgG seroprevalence in hospital staff. METHODS: We conducted cross-sectional surveillance examining seroprevalence of anti-SARS-CoV-2 IgG amongst staff at University Hospitals of Leicester (UHL) NHS Trust. We quantified seroprevalence stratified by ethnicity, occupation and seniority of practitioner and used logistic regression to examine demographic and occupational factors associated with seropositivity. RESULTS: A total of 1148/10662 (10.8%) hospital staff members were seropositive. Compared to White staff (seroprevalence 9.1%), seroprevalence was higher in South Asian (12.3%) and Black (21.2%) staff. The occupations and department with the highest seroprevalence were nurses/healthcare assistants (13.7%) and the Emergency Department (ED)/Acute Medicine (17.5%), respectively. Seroprevalence decreased with seniority in medical/nursing practitioners. Minority ethnicity was associated with seropositivity on an adjusted analysis (South Asian: aOR 1.26; 95%CI: 1.07-1.49 and Black: 2.42; 1.90-3.09). Anaesthetics/ICU staff members were less likely to be seropositive than ED/Acute medicine staff (0.41; 0.27-0.61). CONCLUSIONS: Ethnicity and occupational factors, including specialty and seniority, are associated with seropositivity for anti-SARS-Cov-2 IgG. These findings could be used to inform occupational risk assessments for front-line healthcare workers.

Socio-demographic heterogeneity in the prevalence of COVID-19 during lockdown is associated with ethnicity and household size: Results from an observational cohort study.

BACKGROUND: Accumulating evidence indicates that COVID-19 causes adverse outcomes in ethnic minority groups. However, little is known about the impact of ethnicity and household size on acquiring infection with SARS-CoV-2. METHODS: We undertook a retrospective cohort study, in Leicester (UK), of all individuals assessed for COVID-19 with polymerase chain reaction (PCR) testing at University Hospitals of Leicester NHS Trust between 1st March and 28th April 2020. We used logistic regression to identify sociodemographic, clinical and temporal factors associated with SARS-CoV-2 PCR positivity before/after lockdown. FINDINGS: 971/4051 (24.0%) patients with suspected COVID-19 were found to be PCR positive for SARS-CoV-2. PCR positivity was more common amongst individuals from ethnic minortiy backgrounds than their White counterparts (White 20.0%, South Asian 37.5%, Black 36.1%, Other 32.2%; p<0.001 for all ethnic minority groups vs White). After adjustment, compared to White ethnicity, South Asian (aOR 2.44 95%CI 2.01, 2.97), Black (aOR 2.56 95%CI 1.71, 3.84) and Other (aOR 2.53 95%CI 1.74, 3.70) ethnicities were more likely to test positive, as were those with a larger estimated household size (aOR 1.06 95%CI 1.02, 1.11). We saw increasing proportions of positive tests in the three weeks post-lockdown amongst the ethnic minority , but not the White, cohort. Estimated household size was associated with PCR positivity after, but not before, lockdown (aOR 1.10 95%CI 1.03, 1.16). INTERPRETATION: In individuals presenting with suspected COVID-19, those from ethnic minority communities and larger households had an increased likelihood of SARS-CoV-2 PCR positivity. Pandemic control measures may have more rapid impact on slowing viral transmission amongst those of White ethnicity compared to ethnic minority groups, Research is urgently required to understand the mechanisms underlying these disparities and whether public health interventions have differential effects on individuals from ethnic minority groups. FUNDING: 10.13039/100006662 NIHR.