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Nowcasting transmission and suppression of the Delta variant of SARS-CoV-2 in Australia

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 Added by Mikhail Prokopenko
 Publication date 2021
and research's language is English




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As of July 2021, there is a continuing outbreak of the B.1.617.2 (Delta) variant of SARS-CoV-2 in Sydney, Australia. The outbreak is of major concern as the Delta variant is estimated to have twice the reproductive number to previous variants that circulated in Australia in 2020, which is worsened by low levels of acquired immunity in the population. Using a re-calibrated agent-based model, we explored a feasible range of non-pharmaceutical interventions, in terms of both mitigation (case isolation, home quarantine) and suppression (school closures, social distancing). Our nowcasting modelling indicated that the level of social distancing currently attained in Sydney is inadequate for the outbreak control. A counter-factual analysis suggested that if 80% of agents comply with social distancing, then at least a month is needed for the new daily cases to reduce from their peak to below ten. A small reduction in social distancing compliance to 70% lengthens this period to 45 days.



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SARS-CoV-2 causing COVID-19 disease has moved rapidly around the globe, infecting millions and killing hundreds of thousands. The basic reproduction number, which has been widely used and misused to characterize the transmissibility of the virus, hides the fact that transmission is stochastic, is dominated by a small number of individuals, and is driven by super-spreading events (SSEs). The distinct transmission features, such as high stochasticity under low prevalence, and the central role played by SSEs on transmission dynamics, should not be overlooked. Many explosive SSEs have occurred in indoor settings stoking the pandemic and shaping its spread, such as long-term care facilities, prisons, meat-packing plants, fish factories, cruise ships, family gatherings, parties and night clubs. These SSEs demonstrate the urgent need to understand routes of transmission, while posing an opportunity that outbreak can be effectively contained with targeted interventions to eliminate SSEs. Here, we describe the potential types of SSEs, how they influence transmission, and give recommendations for control of SARS-CoV-2.
There is a continuing debate on relative benefits of various mitigation and suppression strategies aimed to control the spread of COVID-19. Here we report the results of agent-based modelling using a fine-grained computational simulation of the ongoing COVID-19 pandemic in Australia. This model is calibrated to match key characteristics of COVID-19 transmission. An important calibration outcome is the age-dependent fraction of symptomatic cases, with this fraction for children found to be one-fifth of such fraction for adults. We apply the model to compare several intervention strategies, including restrictions on international air travel, case isolation, home quarantine, social distancing with varying levels of compliance, and school closures. School closures are not found to bring decisive benefits, unless coupled with high level of social distancing compliance. We report several trade-offs, and an important transition across the levels of social distancing compliance, in the range between 70% and 80% levels, with compliance at the 90% level found to control the disease within 13--14 weeks, when coupled with effective case isolation and international travel restrictions.
A number of epidemics, including the SARS-CoV-1 epidemic of 2002-2004, have been known to exhibit superspreading, in which a small fraction of infected individuals is responsible for the majority of new infections. The existence of superspreading implies a fat-tailed distribution of infectiousness (new secondary infections caused per day) among different individuals. Here, we present a simple method to estimate the variation in infectiousness by examining the variation in early-time growth rates of new cases among different subpopulations. We use this method to estimate the mean and variance in the infectiousness, $beta$, for SARS-CoV-2 transmission during the early stages of the pandemic within the United States. We find that $sigma_beta/mu_beta gtrsim 3.2$, where $mu_beta$ is the mean infectiousness and $sigma_beta$ its standard deviation, which implies pervasive superspreading. This result allows us to estimate that in the early stages of the pandemic in the USA, over 81% of new cases were a result of the top 10% of most infectious individuals.
Viral transmission pathways have profound implications for public safety; it is thus imperative to establish a complete understanding of viable infectious avenues. Mounting evidence suggests SARS-CoV-2 can be transmitted via the air; however, this has not yet been demonstrated. Here we quantitatively analyze virion accumulation by accounting for aerosolized virion emission and destabilization. Reported superspreading events analyzed within this framework point towards aerosol mediated transmission of SARS-CoV-2. Virion exposure calculated for these events is found to trace out a single value, suggesting a universal minimum infective dose (MID) via aerosol that is comparable to the MIDs measured for other respiratory viruses; thus, the consistent infectious exposure levels and their commensurability to known aerosol-MIDs establishes the plausibility of aerosol transmission of SARS-CoV-2. Using filtration at a rate exceeding the destabilization rate of aerosolized SARS-CoV-2 can reduce exposure below this infective dose.
SARS-CoV-2, like any other virus, continues to mutate as it spreads, according to an evolutionary process. Unlike any other virus, the number of currently available sequences of SARS-CoV-2 in public databases such as GISAID is already several million. This amount of data has the potential to uncover the evolutionary dynamics of a virus like never before. However, a million is already several orders of magnitude beyond what can be processed by the traditional methods designed to reconstruct a viruss evolutionary history, such as those that build a phylogenetic tree. Hence, new and scalable methods will need to be devised in order to make use of the ever increasing number of viral sequences being collected. Since identifying variants is an important part of understanding the evolution of a virus, in this paper, we propose an approach based on clustering sequences to identify the current major SARS-CoV-2 variants. Using a $k$-mer based feature vector generation and efficient feature selection methods, our approach is effective in identifying variants, as well as being efficient and scalable to millions of sequences. Such a clustering method allows us to show the relative proportion of each variant over time, giving the rate of spread of each variant in different locations -- something which is important for vaccine development and distribution. We also compute the importance of each amino acid position of the spike protein in identifying a given variant in terms of information gain. Positions of high variant-specific importance tend to agree with those reported by the USAs Centers for Disease Control and Prevention (CDC), further demonstrating our approach.
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