Randomized Controlled Trial
Study population and setting
This open-label cluster randomized controlled trial of daily testing of close contacts of SARS-CoV-2 cases was conducted in 201 secondary schools and further education colleges (students aged 11 years and older) in England between April and June 2021, during which time the Delta (B.1.617.2) variant was the predominant circulating strain, but community transmission rates were low to moderate. SARS-CoV-2 cases in intervention and control arms were routinely identified through twice weekly asymptomatic testing using lateral flow devices (LFD; i.e., rapid tests) and symptom screening. Schools were randomized such that asymptomatic close contacts of cases in schools were given either 10-day quarantine (control arm) or daily testing with LFD for seven days, excluding weekends (intervention arm). Contacts in the intervention arm could remain in school if they tested negative on the LFD that day (i.e., test-to-stay). LFD testing was done using Orient Gene (Huzhou, China) by school staff on anterior nasal swabs. All individuals with a positive LFD test or with symptoms indicative of SARS-CoV-2 infection were required to isolate and obtain a PCR confirmatory test. Randomization was done at the school level, and stratified based on school type (secondary vs. college), presence of residential students, presence of a 6th form, and the proportion of students eligible for school meals (>17% or ≤17%). Co-primary outcomes were assessed in students and staff at the school-level and included (1) rates of COVID-19 school-related absences and (2) PCR-confirmed COVID-19, adjusted for community case rates. Data on school-related absences were either directly reported by the schools or obtained through government databases, whereas data on PCR-confirmed COVID-19 were obtained solely through the National Health Services (NHS) Test and Trace Program database. The trial was designed as a non-inferiority trial, meaning that it was powered to identify whether the intervention and control arms had similar outcomes rather than, as is more typical, powered to find a difference in the outcomes across arms. Primary analyses were intent-to-treat and done using quasi-Poisson regression. In secondary analyses, efficacy was assessed after adjustment for compliance with the LFD testing intervention, where compliance was defined for individuals as 3 or more LFD tests or an LFD positive test.
Summary of Main Findings
2000 schools were notified of the study, and 201 schools were enrolled and assigned to either the intervention (n=102) or control (n=99) arm. Among these schools, 77% (n=76) in the control arm and 84% (n=86) in the intervention arm directly reported student and staff lists and attendance data. Overall, SARS-CoV-2 transmission from index cases to close contacts was low in intervention and control arms (~2%). Mean compliance with the intervention (i.e., daily LFD testing) was 42% (n=2432/5763 contacts), but compliance varied substantially across schools (median 63%: IQR=40-79%). In primary, intent-to-treat-analyses, COVID-19 school-related absences were non-significantly reduced by 20% in the intervention arm (adjusted incidence rate ratio [IRR] 0.80; 95%CI 0.54-1.19). After adjustment for compliance, there was a greater relative reduction in COVID-19 related school absences observed in the intervention arm (IRR 0.61; 0.30-1.23), but this difference was also not statistically significantly different. In a separate analysis of impact on all-cause school absence rates, there were no differences observed between study arms (0.97; 95%CI: 0.82-1.16). There were also no differences in rates of PCR-confirmed symptomatic infection between study arms (IRR 0.96; 95%CI:0.75-1.22). While cases were more commonly found among students in both arms, intervention efficacy for either of the two primary outcomes did not significantly differ between students and staff. Using data on a subset of PCR-confirmed infections, the LFD rapid was estimated to have 99.93% specificity and 53% sensitivity.
The major strength of this study is that it was a randomized controlled trial. Multiple, independent databases were used to obtain information on the primary outcomes. Infection rates in schools were adjusted for background community transmission rates. Multiple policy relevant outcomes were assessed, and sensitivity analyses conducted. The non-inferiority design was appropriate given the study hypotheses, which were that there would be a reduction in COVID-19 related absences but that there would not be a difference in SARS-CoV-2 transmission across arms.
Compliance with routine asymptomatic testing and symptom screening to identify index cases was reportedly poor, but not quantified in either study arm. Not all schools directly reported data to the study teams, and so intervention compliance could only be assessed from a subset of schools, which likely had higher compliance rates. This study was conducted over a relatively short time frame (~10 weeks), during periods of low/moderate SARS-CoV-2 transmission, and was underpowered to detect modest differences in outcomes between arms. Variability in other transmission control measures (e.g., masking protocols, air circulation protocols, spacing of students in classrooms) across schools was not reported, and so it is possible that there was unmeasured confounding by these measures due to chance imbalances. Given that this study only included secondary schools or higher, the findings may not be applicable to children in primary schools, pre-school, or day care.
This is the first randomized controlled trial to study an intervention to reduce SARS-CoV-2 transmission in an educational setting. Detailed, high quality information on the epidemiology of virus transmission within schools is also provided.
This review was posted on: 11 October 2021