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medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.05.24.21257703


BackgroundCOVID-19 patients shed SARS-CoV-2 RNA in their faeces. We hypothesised that detection of SARS-CoV-2 RNA in wastewater treatment plant (WWTP) influent could be a valuable tool to assist in public health decision making. We aimed to rapidly develop and validate a scalable methodology for the detection of SARS-CoV-2 RNA in wastewater that could be implemented at a national level and to determine the relationship between the wastewater signal and COVID-19 cases in the community. MethodsWe developed a filtration-based methodology for the concentration of SARS-CoV-2 from WWTP influent and subsequent detection and quantification by RT-qPCR. This methodology was used to monitor 28 WWTPs across Scotland, serving 50% of the population. For each WWTP catchment area, we collected data describing COVID-19 cases and deaths. We quantified spatial and temporal relationships between SARS-CoV-2 RNA in wastewater and COVID-19 cases. FindingsDaily WWTP SARS-CoV-2 influent viral RNA load, calculated using daily influent flow rates, had the strongest correlation ({rho}>0.9) with COVID-19 cases within a catchment. As the incidence of COVID-19 cases within a community increased, a linear relationship emerged between cases and influent viral RNA load. There were significant differences between WWTPs in their capacity to predict case numbers based on influent viral RNA load, with the limit of detection ranging from twenty-five cases for larger plants to a single case in smaller plants. InterpretationThe levels of SARS-CoV-2 RNA in WWTP influent provide a cost-effective and unbiased measure of COVID-19 incidence within a community, indicating that national scale wastewater-based epidemiology can play a role in COVID-19 surveillance. In Scotland, wastewater testing has been expanded to cover 75% of the population, with sub-catchment sampling being used to focus surge testing. SARS-CoV-2 variant detection, assessment of vaccination on community transmission and surveillance for other infectious diseases represent promising future applications. FundingThis study was funded by project grants from the Scottish Government via the Centre of Expertise for Waters (CD2019/06) and The Natural Environment Research Councils COVID-19 Rapid Response grants (NE/V010441/1). The Roslin Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council (BB/P013740/1, BBS/E/D/20002173). Sample collection and supplementary analysis was funded and undertaken by Scottish Water and the majority of the sample analysis was funded and undertaken by the Scottish Environment Protection Agency.

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.

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.

medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.11.25.20144139


Restrictions on mobility are a key component of infectious disease controls, preventing the spread of infections to as yet unexposed areas, or to regions which have previously eliminated outbreaks. However, even under the most severe restrictions, some travel must inevitably continue, at the very minimum to retain essential services. For COVID-19, most countries imposed severe restrictions on travel at least as soon as it was clear that containment of local outbreaks would not be possible. Such restrictions are known to have had a substantial impact on the economy and other aspects of human health, and so quantifying the impact of such restrictions is an essential part of evaluating the necessity for future implementation of similar measures. In this analysis, we built a simulation model using National statistical data to record patterns of movements to work, and implement levels of mobility recorded in real time via mobile phone apps. This model was fitted to the pattern of deaths due to COVID-19 using approximate Bayesian inference. Our model is able to recapitulate mortality considering the number of deaths and datazones (DZs, which are areas containing approximately 500-1000 residents) with deaths, as measured across 32 individual council areas (CAs) in Scotland. Our model recreates a trajectory consistent with the observed data until 1st of July. According to the model, most transmission was occurring locally (i.e. in the model, 80% of transmission events occurred within spatially defined communities of approximately 100 individuals). We show that the net effect of the various restrictions put into place in March can be captured by a reduction in transmission down to 12% of its pre-lockdown rate effective 28th March. By comparing different approaches to reducing transmission, we show that, while the timing of COVID-19 restrictions influences the role of the transmission rate on the number of COVID-related deaths, early reduction in long distance movements does not reduce death rates significantly. As this movement of individuals from more infected areas to less infected areas has a minimal impact on transmission, this suggests that the fraction of population already immune in infected communities was not a significant factor in these early stages of the national epidemic even when local clustering of infection is taken into account. The best fit model also shows a considerable influence of the health index of deprivation (part of the index of multiple deprivations or iMD) on mortality. The most likely value has the CA with the highest level of health-related deprivation to have on average, a 2.45 times greater mortality rate due to COVID-19 compared to the CA with the lowest, showing the impact of health-related deprivation even in the early stages of the COVID-19 national epidemic.