The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England 1 , was first identified in the UK in late summer to early autumn 2020 2 . Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.Phylogenetic studies carried out by the UK COVID-19 Genomics Consortium (COG-UK) (https://www.cogconsortium.uk) 8 provided the first indication that B.1.1.7 has an unusual accumulation of substitutions and was growing at a higer rate than other circulating lineages. We investigated time trends in the frequency of sampling VOC genomes and the proportion of PCR tests exhibiting SGTF across the UK, which we calibrated as a biomarker of VOC infection. Using multiple approaches and both genetic and SGTF data, we conclude that B.1.1.7 is associated with a higher reproduction number (R) than previous non-VOC lineages.We examined whole-genome SARS-CoV-2 sequences from randomly sampled residual materials obtained from community-based COVID-19 testing in England, collected between 1 October 2020 and 16 January 2021. These data included 31,390 B.1.1.7 sequences for which the time and location of sample collection were known. Over the same period, 52,795 non-VOC genomes were collected. VOC sequences were initially concentrated in London (n = 9,134), the South East (n = 5,609), and the East of England (n = 4,413), but is now widely distributed across England.

A highly diverse T-cell receptor (TCR) repertoire is a fundamental property of an effective immune system, and is associated with efficient control of viral infections and other pathogens. However, direct measurement of total TCR diversity is impossible. The diversity is high and the frequency distribution of individual TCRs is heavily skewed; the diversity therefore cannot be captured in a blood sample. Consequently, estimators of the total number of TCR clonotypes that are present in the individual, in addition to those observed, are essential. This is analogous to the ‘unseen species problem’ in ecology. We review the diversity (species richness) estimators that have been applied to T-cell repertoires and the methods used to validate these estimators. We show that existing approaches have significant shortcomings, and frequently underestimate true TCR diversity. We highlight our recently developed estimator, DivE, which can accurately estimate diversity across a range of immunological and biological systems.

Background Before the advent of an effective vaccine, nonpharmaceutical interventions, such as mask-wearing, social distancing, and lockdowns, have been the primary measures to combat the COVID-19 pandemic. Such measures are highly effective when there is high population-wide adherence, which requires information on current risks posed by the pandemic alongside a clear exposition of the rules and guidelines in place. Objective Here we analyzed online news media coverage of COVID-19. We quantified the total volume of COVID-19 articles, their sentiment polarization, and leading subtopics to act as a reference to inform future communication strategies. Methods We collected 26 million news articles from the front pages of 172 major online news sources in 11 countries (available online at SciRide). Using topic detection, we identified COVID-19–related content to quantify the proportion of total coverage the pandemic received in 2020. The sentiment analysis tool Vader was employed to stratify the emotional polarity of COVID-19 reporting. Further topic detection and sentiment analysis was performed on COVID-19 coverage to reveal the leading themes in pandemic reporting and their respective emotional polarizations. Results We found that COVID-19 coverage accounted for approximately 25.3% of all front-page online news articles between January and October 2020. Sentiment analysis of English-language sources revealed that overall COVID-19 coverage was not exclusively negatively polarized, suggesting wide heterogeneous reporting of the pandemic. Within this heterogenous coverage, 16% of COVID-19 news articles (or 4% of all English-language articles) can be classified as highly negatively polarized, citing issues such as death, fear, or crisis. Conclusions The goal of COVID-19 public health communication is to increase understanding of distancing rules and to maximize the impact of governmental policy. The extent to which the quantity and quality of information from different communication channels (eg, social media, government pages, and news) influence public understanding of public health measures remains to be established. Here we conclude that a quarter of all reporting in 2020 covered COVID-19, which is indicative of information overload. In this capacity, our data and analysis form a quantitative basis for informing health communication strategies along traditional news media channels to minimize the risks of COVID-19 while vaccination is rolled out.

The UK and Sweden have among the worst per-capita COVID-19 mortality in Europe. Sweden stands out for its greater reliance on voluntary, rather than mandatory, control measures. We explore how the timing and effectiveness of control measures in the UK, Sweden and Denmark shaped COVID-19 mortality in each country, using a counterfactual assessment: what would the impact have been, had each country adopted the others’ policies? Using a Bayesian semi-mechanistic model without prior assumptions on the mechanism or effectiveness of interventions, we estimate the time-varying reproduction number for the UK, Sweden and Denmark from daily mortality data. We use two approaches to evaluate counterfactuals which transpose the transmission profile from one country onto another, in each country’s first wave from 13th March (when stringent interventions began) until 1st July 2020. UK mortality would have approximately doubled had Swedish policy been adopted, while Swedish mortality would have more than halved had Sweden adopted UK or Danish strategies. Danish policies were most effective, although differences between the UK and Denmark were significant for one counterfactual approach only. Our analysis shows that small changes in the timing or effectiveness of interventions have disproportionately large effects on total mortality within a rapidly growing epidemic.

Background: The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. By 24 March 2020, over 440,000 cases and almost 20,000 deaths had been reported worldwide. In response to the fast-growing epidemic, which began in the Chinese city of Wuhan, Hubei, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces. These interventions have impacted economic productivity in China, and the ability of the Chinese economy to resume without restarting the epidemic was not clear. Methods: Using daily reported cases from mainland China and Hong Kong SAR, we estimated transmissibility over time and compared it to daily within-city movement, as a proxy for economic activity. Results: Initially, within-city movement and transmission were very strongly correlated in the five mainland provinces most affected by the epidemic and Beijing. However, that correlation decreased rapidly after the initial sharp fall in transmissibility. In general, towards the end of the study period, the correlation was no longer apparent, despite substantial increases in within-city movement. A similar analysis for Hong Kong shows that intermediate levels of local activity were maintained while avoiding a large outbreak. At the very end of the study period, when China began to experience the re-introduction of a small number of cases from Europe and the United States, there is an apparent up-tick in transmission. Conclusions: Although these results do not preclude future substantial increases in incidence, they suggest that after very intense social distancing (which resulted in containment), China successfully exited its lockdown to some degree. Elsewhere, movement data are being used as proxies for economic activity to assess the impact of interventions. The results presented here illustrate how the eventual decorrelation between transmission and movement is likely a key feature of successful COVID-19 exit strategies.

ObjectiveTo measure the effects of the tier system on the COVID-19 pandemic in the UK between the first and second national lockdowns, before the emergence of the B.1.1.7 variant of concern.DesignThis is a modelling study combining estimates of real-time reproduction number Rt (derived from UK case, death and serological survey data) with publicly available data on regional non-pharmaceutical interventions. We fit a Bayesian hierarchical model with latent factors using these quantities to account for broader national trends in addition to subnational effects from tiers.SettingThe UK at lower tier local authority (LTLA) level. 310 LTLAs were included in the analysis.Primary and secondary outcome measuresReduction in real-time reproduction number Rt.ResultsNationally, transmission increased between July and late September, regional differences notwithstanding. Immediately prior to the introduction of the tier system, Rt averaged 1.3 (0.9–1.6) across LTLAs, but declined to an average of 1.1 (0.86–1.42) 2 weeks later. Decline in transmission was not solely attributable to tiers. Tier 1 had negligible effects. Tiers 2 and 3, respectively, reduced transmission by 6% (5%–7%) and 23% (21%–25%). 288 LTLAs (93%) would have begun to suppress their epidemics if every LTLA had gone into tier 3 by the second national lockdown, whereas only 90 (29%) did so in reality.ConclusionsThe relatively small effect sizes found in this analysis demonstrate that interventions at least as stringent as tier 3 are required to suppress transmission, especially considering more transmissible variants, at least until effective vaccination is widespread or much greater population immunity has amassed.

Human T-lymphotropic virus type-1 (HTLV-1) persists within hosts via infectious spread (de novo infection) and mitotic spread (infected cell proliferation), creating a population structure of multiple clones (infected cell populations with identical genomic proviral integration sites). The relative contributions of infectious and mitotic spread to HTLV-1 persistence are unknown, and will determine the efficacy of different approaches to treatment. The prevailing view is that infectious spread is negligible in HTLV-1 persistence beyond early infection. However, in light of recent high-throughput data on the abundance of HTLV-1 clones, and recent estimates of HTLV-1 clonal diversity that are substantially higher than previously thought (typically between 10 4 and 10 5 HTLV-1 + T cell clones in the body of an asymptomatic carrier or patient with HTLV-1-associated myelopathy/tropical spastic paraparesis), ongoing infectious spread during chronic infection remains possible. We estimate the ratio of infectious to mitotic spread using a hybrid model of deterministic and stochastic processes, fitted to previously published HTLV-1 clonal diversity estimates. We investigate the robustness of our estimates using three alternative estimators. We find that, contrary to previous belief, infectious spread persists during chronic infection, even after HTLV-1 proviral load has reached its set point, and we estimate that between 100 and 200 new HTLV-1 clones are created and killed every day. We find broad agreement between all estimators. The risk of HTLV-1-associated malignancy and inflammatory disease is strongly correlated with proviral load, which in turn is correlated with the number of HTLV-1-infected clones, which are created by de novo infection. Our results therefore imply that suppression of de novo infection may reduce the risk of malignant transformation.

CYD-TDV is the first licensed dengue vaccine for individuals 9–45 (or 60) years of age. Using 12% of the subjects enroled in phase-2b and phase-3 trials for which baseline serostatus was measured, the vaccine-induced protection against virologically confirmed dengue during active surveillance (0–25 months) was found to vary with prior exposure to dengue. Because age and dengue exposure are highly correlated in endemic settings, refined insight into how efficacy varies by serostatus and age is essential to understand the increased risk of hospitalisation observed among vaccinated individuals during the long-term follow-up and to develop safe and effective vaccination strategies. Here we apply machine learning to impute the baseline serostatus for subjects with post-dose 3 titres but missing baseline serostatus. We find evidence for age dependence in efficacy independent of serostatus and estimate that among 9–16 year olds, CYD-TDV is protective against serotypes 1, 3 and 4 regardless of baseline serostatus.