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arxiv; 2022.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2211.13704v1


In this paper we used an adapted version of an existing simulation model of SARS-CoV-2 transmission in Scotland to investigate the rise of the Omicron variant of concern, in order to evaluate plausible scenarios for transmission advantage and vaccine immune escape relative to the Delta variant. We also explored possible outcomes of different levels of imposed non-pharmaceutical intervention. The initial results of these scenarios were used to inform the Scottish Government in the early outbreak stages of the Omicron variant. We use an explicitly spatial agent-based simulation model combined with spatially fine-grained COVID-19 observation data from Public Health Scotland. Using the model with parameters fit over the Delta variant epidemic, some initial assumptions about Omicron transmission advantage and vaccine escape, and a simple growth rate fitting procedure, we were able to capture the initial outbreak dynamics for Omicron. We also find the modelled dynamics hold up to retrospective scrutiny. We found that the modelled imposition of extra non-pharmaceutical interventions planned by the Scottish Government at the time would likely have little effect in light of the transmission advantage held by the Omicron variant and the fact that the planned interventions would have occurred too late in the outbreak's trajectory. Finally, we found that any assumptions made about the projected distribution of vaccines in the model population had little bearing on the outcome, in terms of outbreak size and timing, rather that the detailed landscape of immunity prior to the outbreak was of far greater importance.

medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.08.03.22278013


For a disease such as COVID-19, it is important to identify individuals in a population at heightened risk of infection, as well as broader patterns of infection spread. This is both to estimate burden on healthcare systems (given substantial variation in disease severity from person to person), and to better control the spread of infection. In Scotland, the circulation of SARS-CoV-2 continues to place sustained pressure on healthcare systems, even after a comprehensive vaccination programme and earlier strict non-pharmaceutical interventions. To better understand individuals at heightened risk, we analyse the spatio-temporal distribution of over 450,000 cases of COVID-19 registered in Scotland in the waves of the B.1.1.529 Omicron lineage from November 2021, and an earlier wave of the B.1.617.2 Delta lineage from May 2021. These cases are taken from a uniquely fine scale national data set specifying individual tests. We use random forest regression on local case numbers, informing the model with measures relating to local geography, demographics, deprivation, COVID-19 testing and vaccination coverage. We can then identify broader risk factors indicative of higher case numbers. Despite the Delta and Omicron waves occurring around six months apart, with different control measures and immunity from vaccination and prior infection, the overall risk factors remained broadly similar for both. We find that finer details and clusters in the case distribution are only adequately explained when incorporating a combination of all these factors, implying that variation in COVID-19 cases results from a complex interplay of individual-level behaviour, existing immunity, and willingness to test for COVID-19 at all. On comparing testing patterns to subsequent COVID-19 hospitalisations, we conjecture that the distribution of cases may not be representative of the wider pattern of infection, particularly with respect to local deprivation.

medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.01.08.20248677


The second SARS virus, SARS-CoV-2, emerged in December 2019, and within a month was globally distributed. It was first introduced into Scotland in February 2020 associated with returning travellers and visitors. By March it was circulating in communities across the UK, and to control COVID-19 cases, and prevent overwhelming of the National Health Service (NHS), a 'lockdown' was introduced on 23rd March 2020 with a restriction of people's movements. To augment the public health efforts a large-scale genome epidemiology effort (as part of the COVID-19 Genomics UK (COG-UK) consortium) resulted in the sequencing of over 5000 SARS-CoV-2 genomes by 18th August 2020 from Scottish cases, about a quarter of the estimated number of cases at that time. Here we quantify the geographical origins of the first wave introductions into Scotland from abroad and other UK regions, the spread of these SARS-CoV-2 lineages to different regions within Scotland (defined at the level of NHS Health Board) and the effect of lockdown on virus 'success'. We estimate that approximately 300 introductions seeded lineages in Scotland, with around 25% of these lineages composed of more than five viruses, but by June circulating lineages were reduced to low levels, in line with low numbers of recorded positive cases. Lockdown was, thus, associated with a dramatic reduction in infection numbers and the extinguishing of most virus lineages. Unfortunately since the summer cases have been rising in Scotland in a second wave, with >1000 people testing positive on a daily basis, and hospitalisation of COVID-19 cases on the rise again. Examining the available Scottish genome data from the second wave, and comparing it to the first wave, we find that while some UK lineages have persisted through the summer, the majority of lineages responsible for the second wave are new introductions from outside of Scotland and many from outside of the UK. This indicates that, while lockdown in Scotland is directly linked with the first wave case numbers being brought under control, travel-associated imports (mostly from Europe or other parts of the UK) following the easing of lockdown are responsible for seeding the current epidemic population. This demonstrates that the impact of stringent public health measures can be compromised if following this, movements from regions of high to low prevalence are not minimised.

59585 , 50495
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.01.19.427373


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.

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