Viral burdens are associated with age and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection related sampling bias. (preprint)

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burdens, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. Analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior infection, the average Ct value was 0.94 lower among Alpha variant infections, compared those with the predecessor strain, B.1.177. However, among vaccinated individuals, it was 0.34 lower among Delta variant infections, compared to those with the Alpha variant. In addition, the average Ct value decreased by 0.20 for every 10 year age increment of the infected individual. In summary, within-host viral burdens are associated with age, in addition to the interplay of vaccination status and viral variant.

Analysis and comprehensive lineage identification for SARS-CoV-2 genomes through scalable learning methods (preprint)

Since its emergence in late 2019, SARS-CoV-2 has diversified into a large number of lineages and globally caused multiple waves of infection. Lineages have the potential to spread rapidly and internationally if they have higher intrinsic transmissibility and/or can evade host immune responses, as has been seen with the Alpha, Delta, and Omicron variants of concern (VoCs). Phylogenetic methods provide the gold standard for representing the global diversity of SARS-CoV-2 and to identify newly emerging lineages. However, these methods are computationally expensive, struggle when datasets get too large, and require manual curation to designate new lineages. These issues will only intensify as the vast number of SARS-CoV-2 genomes already available continues to grow. It will therefore be beneficial to develop complementary methods that can incorporate all of the genetic data available, without down sampling, to extract meaningful information rapidly and with minimal curation. Here, we demonstrate the utility of using algorithmic approaches based on word-statistics to represent whole sequences, bringing speed, scalability, and interpretability to the construction of genetic topologies, and that can be used to augment traditional classification practice based on phylogeny.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant (preprint)

We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average ~1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant (preprint)

Summary We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average ∼1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.

Epidemiological and public health requirements for COVID-19 contact tracing apps and their evaluation (preprint)

Digital contact tracing is a public health intervention. It should be integrated with local health policy, provide rapid and accurate notifications to exposed individuals, and encourage high app uptake and adherence to quarantine. Real-time monitoring and evaluation of effectiveness of app-based contact tracing is key for improvement and public trust.

OpenABM-Covid19 - an agent-based model for non-pharmaceutical interventions against COVID-19 including contact tracing (preprint)

SARS-CoV-2 has spread across the world, causing high mortality and unprecedented restrictions on social and economic activity. Policymakers are assessing how best to navigate through the ongoing epidemic, with models being used to predict the spread of infection and assess the impact of public health measures. Here, we present OpenABM-Covid19: an agent-based simulation of the epidemic including detailed age-stratification and realistic social networks. By default the model is parameterised to UK demographics and calibrated to the UK epidemic, however, it can easily be re-parameterised for other countries. OpenABM-Covid19 can evaluate non-pharmaceutical interventions, including both manual and digital contact tracing. It can simulate a population of 1 million people in seconds per day allowing parameter sweeps and formal statistical model-based inference. The code is open-source and has been developed by teams both inside and outside academia, with an emphasis on formal testing, documentation, modularity and transparency. A key feature of OpenABM-Covid19 is its Python interface, which has allowed scientists and policymakers to simulate dynamic packages of interventions and help compare options to suppress the COVID-19 epidemic.