Caveats on COVID-19 herd immunity threshold: the Spain case

After a year of living with the COVID-19 pandemic and its associated consequences, hope looms on the horizon thanks to vaccines. The question is what percentage of the population needs to be immune to reach herd immunity, that is to avoid future outbreaks. The answer depends on the basic reproductive number, R0, a key epidemiological parameter measuring the transmission capacity of a disease. In addition to the virus itself, R0 also depends on the characteristics of the population and their environment. Additionally, the estimate of R0 depends on the methodology used, the accuracy of data and the generation time distribution. This study aims to reflect on the difficulties surrounding R0 estimation, and provides Spain with a threshold for herd immunity, for which we considered the different combinations of all the factors that affect the R0 of the Spanish population. Estimates of R0 range from 1.39 to 3.10 for the ancestral SARS-CoV-2 variant, with the largest differences produced by the method chosen to estimate R0. With these values, the herd immunity threshold (HIT) ranges from 28.1 to 67.7%, which would have made 70% a realistic upper bound for Spain. However, the imposition of the delta variant (B.1.617.2 lineage) in late summer 2021 may have expanded the range of R0 to 4.02–8.96 and pushed the upper bound of the HIT to 90%.

Estimation of the test to test distribution as a proxy for generation interval distribution for the Omicron variant in England

Background Early estimates from South Africa indicated that the Omicron COVID-19 variant may be both more transmissible and have greater immune escape than the previously dominant Delta variant. The rapid turnover of the latest epidemic wave in South Africa as well as initial evidence from contact tracing and household infection studies has prompted speculation that the generation time of the Omicron variant may be shorter in comparable settings than the generation time of the Delta variant. Methods We estimated daily growth rates for the Omicron and Delta variants in each UKHSA region from the 23rd of November to the 23rd of December 2021 using surveillance case counts by date of specimen and S-gene target failure status with an autoregressive model that allowed for time-varying differences in the transmission advantage of the Delta variant where the evidence supported this. By assuming a gamma distributed generation distribution we then estimated the generation time distribution and transmission advantage of the Omicron variant that would be required to explain this time varying advantage. We repeated this estimation process using two different prior estimates for the generation time of the Delta variant first based on household transmission and then based on its intrinsic generation time. Results Visualising our growth rate estimates provided initial evidence for a difference in generation time distributions. Assuming a generation time distribution for Delta with a mean of 2.5-4 days (90% credible interval) and a standard deviation of 1.9-3 days we estimated a shorter generation time distribution for Omicron with a mean of 1.5-3.2 days and a standard deviation of 1.3-4.6 days. This implied a transmission advantage for Omicron in this setting of 160%-210% compared to Delta. We found similar relative results using an estimate of the intrinsic generation time for Delta though all estimates increased in magnitude due to the longer assumed generation time. Conclusions We found that a reduction in the generation time of Omicron compared to Delta was able to explain the observed variation over time in the transmission advantage of the Omicron variant. However, this analysis cannot rule out the role of other factors such as differences in the populations the variants were mixing in, differences in immune escape between variants or bias due to using the test to test distribution as a proxy for the generation time distribution.

Preliminary modeling estimates of the relative transmissibility and immune escape of the Omicron SARS-CoV-2 variant of concern in South Africa

We develop a stochastic, multi-strain, compartmental epidemic model to estimate the relative transmissibility and immune escape of the Omicron variant of concern (VOC) in South Africa. The model integrates population, non-pharmaceutical interventions, vaccines, and epidemiological data and it is calibrated in the period May 1st, 2021 - November 23rd, 2021. We explore a parameter space of relative transmissibility with respect to the Delta variant and immune escape for Omicron by assuming an initial seeding, from unknown origin, in the first week of October 2021. We identify a region of the parameter space where combinations of relative transmissibility and immune escape are compatible with the growth of the epidemic wave. We also find that changes in the generation time associated with Omicron infections strongly affect the results concerning its relative transmissibility. The presented results are informed by current knowledge of Omicron and subject to changes.

Constituent vs Dependency Parsing-Based RDF Model Generation from Dengue Patients’ Case Sheets

Electronic Health Record (EHR) systems in healthcare organisations are primarily maintained in isolation from each other that makes interoperability of unstructured(text) data stored in these EHR systems challenging in the healthcare domain. Similar information may be described using different terminologies by different applications that can be evaded by transforming the content into the Resource Description Framework (RDF) model that is interoperable amongst organisations. RDF requires a document’s contents to be translated into a repository of triplets (subject, predicate, object) known as RDF statements. Natural Language Processing (NLP) techniques can help get actionable insights from these text data and create triplets for RDF model generation. This paper discusses two NLP-based approaches to generate the RDF models from unstructured patients’ documents, namely dependency structure-based and constituent(phrase) structure-based parser. Models generated by both approaches are evaluated in two aspects: exhaustiveness of the represented knowledge and the model generation time. The precision measure is used to compute the models’ exhaustiveness in terms of the number of facts that are transformed into RDF representations.

Estimating the transmissibility of SARS-CoV-2 VOC 202012/01 in Japan using travel history information

<abstract> <p>Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly spread across the globe. The variant of concern (VOC) 202012/01 (B.1.1.7, also known as the alpha variant) bearing the N501Y mutation emerged in late 2020. VOC 202012/01 was more transmissible than existing SARS-CoV-2 variants and swiftly became dominant in many regions. More than 150 cases of VOC 202012/01 were reported in Japan by 26 February 2021. During the very early stage of introduction, only a subset arose from domestic transmission. If the reproduction number <italic>R</italic> (i.e., the average number of secondary transmission events caused by a single primary case) is greater than 1, the corresponding proportion should converge to 1 in a short period of time, and thus it is critical to understand the transmissibility of VOC 202012/01 based on travel history information. The present study aimed to estimate <italic>R</italic> of VOC 202012/01 using overseas travel history information. A mathematical model was developed to capture the relationship between travel history and <italic>R</italic>. We obtained travel history data for each confirmed case of VOC 202012/01 infection from 26 December 2020 to 26 February 2021. Maximum likelihood estimation was used to estimate <italic>R</italic>, accounting for right censoring during real-time estimation. In the baseline scenario, <italic>R</italic> was estimated at 2.11 (95% confidence interval: 1.63, 2.94). By 26 February 2021, an average of nine generations had elapsed since the first imported case. If the generation time of VOC 202012/01 was assumed to be longer, <italic>R</italic> was increased, consistent with estimates of <italic>R</italic> from case data. The estimated <italic>R</italic> of VOC 202012/01 in Japan exceeded 1 on 26 February 2021, suggesting that domestic transmission events caused a major epidemic. Moreover, because our estimate of <italic>R</italic> was dependent on generation time and ascertainment biases, continuous monitoring of contact tracing data is crucial to decipher the mechanisms of increased VOC 202012/01 transmissibility.</p> </abstract>

Selection for infectivity profiles in slow and fast epidemics, and the rise of SARS-CoV-2 variants

Evaluating the characteristics of emerging SARS-CoV-2 variants of concern is essential to inform pandemic risk assessment. A variant may grow faster if it produces a larger number of secondary infections (transmissibility advantage) or if the timing of secondary infections (generation time) is better. So far, assessments have largely focused on deriving the transmissibility advantage assuming the generation time was unchanged. Yet, knowledge of both is needed to anticipate impact. Here we develop an analytical framework to investigate the contribution of both the transmissibility advantage and generation time to the growth advantage of a variant. We find that the growth advantage depends on the epidemiological context (level of epidemic control). More specifically, variants conferring earlier transmission are more strongly favoured when the historical strains have fast epidemic growth, while variants conferring later transmission are more strongly favoured when historical strains have slow or negative growth. We develop these conceptual insights into a statistical framework to infer both the transmissibility advantage and generation time of a variant. On simulated data, our framework correctly estimates both parameters when it covers time periods characterized by different epidemiological contexts. Applied to data for the Alpha and Delta variants in England and in Europe, we find that Alpha confers a +54% [95% CI, 45-63%] transmissibility advantage compared to previous strains, and Delta +140% [98-182%] compared to Alpha, and mean generation times are similar to historical strains for both variants. This work helps interpret variant frequency and will strengthen risk assessment for future variants of concern.

A new protocol for speed vernalisation of winter cereals

There are many challenges facing the development of high-yielding, nutritious crops for future environments. One limiting factor is generation time, which prolongs research and plant breeding timelines. Recent advances in speed breeding protocols have dramatically reduced generation time for many short-day and long-day species by optimising light and temperature conditions during plant growth. However, winter crops with a vernalisation requirement still require up to 6–10 weeks in low-temperature conditions before transition to reproductive development. Here, we tested a suite of environmental conditions and protocols to investigate if vernalisation can be satisfied more efficiently. We identified a vernalisation method consisting of exposing seeds at the soil surface to an extended photoperiod of 22 h day:2 h night at 10°C with transfer to speed breeding conditions that dramatically reduces generation time in both winter wheat (Triticum aestivum) and winter barley (Hordeum vulgare). Implementation of this protocol achieved up to five generations per year for winter wheat or barley, instead of the two typically obtained under standard vernalisation and plant growth conditions. The protocol has great potential to enhance training and to accelerate research, pre-breeding, and breeding outcomes focussed on winter crop improvement.

Estimating the increase in reproduction number associated with the Delta variant using local area dynamics in England

BackgroundLocal estimates of the time-varying effective reproduction number (Rt) of COVID-19 in England became increasingly heterogeneous during April and May 2021. This may have been attributable to the spread of the Delta SARS-CoV-2 variant. This paper documents real-time analysis that aimed to investigate the association between changes in the proportion of positive cases that were S-gene positive, an indicator of the Delta variant against a background of the previously predominant Alpha variant, and the estimated time-varying Rt at the level of upper-tier local authorities (UTLA).MethodWe explored the relationship between the proportion of samples that were S-gene positive and the Rt of test-positive cases over time from the 23 February 2021 to the 25 May 2021. Effective reproduction numbers were estimated using the EpiNow2 R package independently for each local authority using two different estimates of the generation time. We then fit a range of regression models to estimate a multiplicative relationship between S-gene positivity and weekly mean Rt estimate.ResultsWe found evidence of an association between increased mean Rt estimates and the proportion of S-gene positives across all models evaluated with the magnitude of the effect increasing as model flexibility was decreased. Models that adjusted for either national level or NHS region level time-varying residuals were found to fit the data better, suggesting potential unexplained confounding.ConclusionsOur results indicated that even after adjusting for time-varying residuals between NHS regions, S-gene positivity was associated with an increase in the effective reproduction number of COVID-19. These findings were robust across a range of models and generation time assumptions, though the specific effect size was variable depending on the assumptions used. The lower bound of the estimated effect indicated that the reproduction number of Delta was above 1 in almost all local authorities throughout the period of investigation.