Mitigating isolation: further comparing the effect of LFD testing for early release from self-isolation for COVID-19 cases

In a recent paper, we described how lateral flow device (LFD) testing might be used to reduce the amount of excess time individuals spend in isolation following confirmation of a COVID-19 infection. Through the work presented here, we look to expand upon this and explore in more detail the benefit that such an approach might provide. We use our previously described model to study scenarios through the metrics "proportion released still infectious", "excess time spent in isolation" (time isolated while no longer infectious), and "time spent infectious after early release". We also look to consider the effect on these metrics by comparing values obtained when a single negative LFD test is required for early release, versus requiring two and three sequential negative LFD tests. Results show that jointly employing self-isolation and LFD testing may deliver sizeable reductions to the proportion of individuals being release while still infection, the average amount of excess time spent in isolation by those no longer a public health threat, and the average amount of time spent infectious by those released early. These effects considered in conjunction could provide a considerable decrease in the public health risk posed by still infectious individuals being released back into the population by actively monitoring their infection status throughout their isolation period. Such an approach could also help lighten the impact incurred on the individual by reducing the amount of time spent in isolation while posing no further public health risk, in addition to alleviating pressures on the economy and in healthcare settings caused by mass isolation in times of high prevalence.

Mitigating isolation: The use of rapid antigen testing to reduce the impact of self-isolation periods

Isolating, either enforced or self-guided, is a well-recognised and used technique in the limitation and reduction of disease spread. This usually balances the societal harm of disease transmission against the individual harm of being isolated and is typically limited to a very small number of individuals. With the widespread transmission of SARS-CoV-2 and requirements to self-isolate when symptomatic or having tested positive, the number of people affected has grown very large causing noticeable individual cost, and disruption to the provision of essential services. With widespread access to reliable rapid antigen tests (also known as LFD or LFTs), in this paper we examine strategies to utilise this testing technology to limit the individual harm whist maintaining the protective effect of isolation. We extend this work to examine how isolation may be improved and mitigate the release of infective individuals into the population caused by fixed time-periods.

Statistical Design and Analysis of PCR Tests for Fast Mutating Viruses

As the SARS-CoV-2 virus mutates, mutations harboured in patients become increasingly diverse. Patients classified into two strains may have overlapping non-variant-defining mutations. Mutation calling by sequencing is relative to a reference genome. As SARS-CoV-2 mutates, tracking emerging mutant strains may become increasingly problematic if the reference genome remains Wuhan-Hu-1, because the comparison then becomes indirect: current dominant strain relative to Wuhan-Hu-1 versus emerging strain relative to Wuhan-Hu-1. The original Thermo Fishers TaqPath PCR test, on which the UK has standardized national testing of SARS-CoV-2 primarily, targets Wuhan-Hu-1. PCR targets appear readily updated, as TaqPath 2.0 now targets both currently known and future SARS-CoV-2 mutations, probing the N gene and ORF1ab but not the S gene, with 8 probes instead of the original 3 probes. Going forward, our statistical method can more directly compare current wildtype versus emerging mutants, since our new method can use any pair of probes updated to probe the current wildtype and anticipated mutations. The fact that patients harbour mixtures of mutations allows our statistical methods to potentially catch emerging mutants. Given a PCR test which targets the current dominant strain (current wildtype), our statistical method can potentially directly differentiate the current wildtype from an emerging strain.

SARS-CoV-2 infectivity by viral load, S gene variants and demographic factors and the utility of lateral flow devices to prevent transmission

BackgroundHow SARS-CoV-2 infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect sensitivity is unknown. MethodsWe combined SARS-CoV-2 testing and contact tracing data from England between 01-September-2020 and 28-February-2021. We used multivariable logistic regression to investigate relationships between PCR-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using one of four LFDs. Results231,498/2,474,066 (9%) contacts of 1,064,004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower Ct values) e.g., 11.7%(95%CI 11.5-12.0%) at Ct=15 and 4.5%(4.4-4.6%) at Ct=30. B.1.1.7 infection increased PCR-positive results by [~]50%, (e.g. 1.55-fold, 95%CI 1.49-1.61, at Ct=20). PCR-positive results were most common in household contacts (at Ct=20.1, 8.7%[95%CI 8.6-8.9%]), followed by household visitors (7.1%[6.8-7.3%]), contacts at events/activities (5.2%[4.9-5.4%]), work/education (4.6%[4.4-4.8%]), and least common after outdoor contact (2.9%[2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5%(89.4-89.6%) and 83.0%(82.8-83.1%) of cases with PCR-positive contacts respectively. ConclusionsSARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by [~]50%. The best performing LFDs detect most infectious cases. Key pointsIn 2,474,066 contacts of 1,064,004 SARS-CoV-2 cases, PCR-positive tests in contacts increased with higher index case viral loads, the B.1.1.7 variant and household contact. Children were less infectious. Lateral flow devices can detect 83.0-89.5% of infections leading to onward transmission.

Real-time Nowcasting and Forecasting of COVID-19 Dynamics in England: the first wave?

England has been heavily affected by the SARS-CoV-2 pandemic, with severe lock-down mitigation measures now gradually being lifted. The real-time pandemic monitoring presented here has contributed to the evidence informing this pandemic management. Estimates on the 10th May showed lock-down had reduced transmission by 75%, the reproduction number falling from 2.6 to 0.61. This regionally-varying impact was largest in London of 81% (95% CrI: 77%-84%). Reproduction numbers have since slowly increased, and on 19th June the probability that the epidemic is growing was greater than 5% in two regions, South West and London. An estimated 8% of the population had been infected, with a higher proportion in London (17%). The infection-to-fatality ratio is 1.1% (0.9%-1.4%) overall but 17% (14%-22%) among the over-75s. This ongoing work will be key to quantifying any widespread resurgence should accrued immunity and effective contact tracing be insufficient to preclude a second wave.

Rapid increase of Care Homes reporting outbreaks a sign of eventual substantial disease burden

Enclosed societies (i.e. locations that are connected to wider community only by subgroups of their population and that are dominated by within society transmission) have the potential, upon establishment of a respiratory disease, to suffer a large proportion of the population within becoming infected. Care homes are particularly susceptible to COVID19 outbreaks and suffer high mortality due to vulnerable population within. Recent data on the number of new outbreak reports in care homes to Public Health England shows an initial increase then plateau perhaps associated with an SIS model dynamic. Without change in policy moving forward a high prevalence in such setting is predicted of around 75%. Action is needed to support staff in such settings.