Assessing the impact of Australia's mass vaccination campaigns over the Delta and Omicron outbreaks.

BACKGROUND: The Australian Government implemented a national vaccination campaign against COVID-19 beginning February 22, 2021. The roll-out was criticised for being delayed relative to many high-income countries, but high levels of vaccination coverage were belatedly achieved. The large-scale Omicron outbreak in January 2022 resulted in a massive number of cases and deaths, although mortality would have been far higher if not for vigorous efforts to rapidly vaccinate the entire population. The impact of the vaccination coverage was assessed over this extended period. METHODS: We considered NSW, as the Australian jurisdiction with the highest quality data for our purposes and which still reflected the national experience. Weekly death rates were derived among individuals aged 50+ with respect to vaccine status between August 8, 2021 and July 9, 2022. We evaluated deaths averted by the vaccination campaign by modelling alternative counterfactual scenarios based on a simple data-driven modelling methodology presented by Jia et al. (2023). FINDINGS: Unvaccinated individuals had a 7.7-fold greater mortality rate than those who were fully vaccinated among people aged 50+, which rose to 11.2-fold in those who had received a booster dose. If NSW had fully vaccinated its ~2.9 million 50+ residents earlier (by July 28, 2021), only 440 of the total 3,495 observed 50+ deaths would have been averted. Up to July 9, 2022, the booster campaign prevented 1,860 deaths. In the absence of a vaccination campaign, ~21,250 COVID-19 50+ deaths (conservative estimate) could have been expected in NSW i.e., some 6 times the actual total. We also find the methodology of Jia et al. (2023) can sometimes significantly underestimate that actual number. INTERPRETATION: The Australian vaccination campaign was successful in reducing mortality over 2022, relative to alternative hypothetical vaccination scenarios. The success was attributable to the Australian public's high levels of engagement with vaccination in the face of new SARS-COV-2 variants, and because high levels of vaccination coverage (full and booster) were achieved in the period shortly before the major Omicron outbreak of 2022.

Modelling the unexpected dynamics of COVID-19 in Manaus, Brazil.

In late March 2020, SARS-CoV-2 arrived in Manaus, Brazil, and rapidly developed into a large-scale epidemic that collapsed the local health system and resulted in extreme death rates. Several key studies reported that ∼76% of residents of Manaus were infected (attack rate AR≃76%) by October 2020, suggesting protective herd immunity had been reached. Despite this, an unexpected second wave of COVID-19 struck again in November and proved to be larger than the first, creating a catastrophe for the unprepared population. It has been suggested that this could be possible if the second wave was driven by reinfections. However, it is widely reported that reinfections were at a low rate (before the emergence of Omicron), and reinfections tend to be mild. Here, we use novel methods to model the epidemic from mortality data without considering reinfection-caused deaths and evaluate the impact of interventions to explain why the second wave appeared. The method fits a "flexible" reproductive number R0(t) that changes over the epidemic, and it is demonstrated that the method can successfully reconstruct R0(t) from simulated data. For Manaus, the method finds AR≃34% by October 2020 for the first wave, which is far less than required for herd immunity yet in-line with seroprevalence estimates. The work is complemented by a two-strain model. Using genomic data, the model estimates transmissibility of the new P.1 virus lineage as 1.9 times higher than that of the non-P.1. Moreover, an age class model variant that considers the high mortality rates of older adults show very similar results. These models thus provide a reasonable explanation for the two-wave dynamics in Manaus without the need to rely on large reinfection rates, which until now have only been found in negligible to moderate numbers in recent surveillance efforts.

The immune evasion ability of Delta variant is comparable to that of Beta variant in South Africa.

BACKGROUND: The high immune evasion ability of SARS-COV-2 Omicron variant surprised the world and appears to be far stronger than any previous variant. Previous to Omicron it has been difficult to assess and compare immune evasion ability of different variants, including the Beta and Delta variants, because of the relatively small numbers of reinfections and because of the problems in correctly identifying reinfections in the population. This has led to different claims appearing in the literature. Thus we find claims of both high and low immune evasion for the Beta variant. Some findings have suggested that the Beta variant has a higher immune evasion ability than the Delta variant in South Africa, and others that it has a lower ability. METHOD: In this brief report, we re-analyse a unique dataset of variant-specific reinfection data and a simple model to correct for the infection attack rates of different variants. RESULT: We find that a model with the Delta variant having  an equal or higher immune evasion ability than Beta variant is compatible with the data. CONCLUSION: We conclude that the immune evasion ability of Beta variant is not stronger than Delta variant, and indeed, the immune evasion abilities of both variants are weak in South Africa.

Resolving the enigma of Iquitos and Manaus: A modeling analysis of multiple COVID-19 epidemic waves in two Amazonian cities.

The two nearby Amazonian cities of Iquitos and Manaus endured explosive COVID-19 epidemics and may well have suffered the world's highest infection and death rates over 2020, the first year of the pandemic. State-of-the-art epidemiological and modeling studies estimated that the populations of both cities came close to attaining herd immunity (>70% infected) at the termination of the first wave and were thus protected. This makes it difficult to explain the more deadly second wave of COVID-19 that struck again in Manaus just months later, simultaneous with the appearance of a new P.1 variant of concern, creating a catastrophe for the unprepared population. It was suggested that the second wave was driven by reinfections, but the episode has become controversial and an enigma in the history of the pandemic. We present a data-driven model of epidemic dynamics in Iquitos, which we also use to explain and model events in Manaus. By reverse engineering the multiple epidemic waves over 2 y in these two cities, the partially observed Markov process model inferred that the first wave left Manaus with a highly susceptible and vulnerable population (≈40% infected) open to invasion by P.1, in contrast to Iquitos (≈72% infected). The model reconstructed the full epidemic outbreak dynamics from mortality data by fitting a flexible time-varying reproductive number [Formula: see text] while estimating reinfection and impulsive immune evasion. The approach is currently highly relevant given the lack of tools available to assess these factors as new SARS-CoV-2 virus variants appear with different degrees of immune evasion.

Rapid global spread of variants of concern of SARS-CoV-2.

Objectives: Variants of concern (VOCs) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), such as the Delta variant and the Omicron variant, have reached all countries/regions of the world and have had a tremendous impact. This study analyses the global spread of VOCs of SARS-CoV-2. Methods: Biweekly aggregated numbers of several VOCs were retrieved for 58 locations. The time interval for the proportion of VOC samples to exceed 60% (indicating dominance) among all samples sequenced in each location was calculated. The times taken for a VOC to become dominant in 12 (or 36) locations was defined in order to quantify the speed of spread. Results: It took 63, 56 and 28 days for the Alpha, Delta and Omicron variants to become dominant in 12 locations, respectively, and 133, 70 and 28 days for the Alpha, Delta and Omicron variants to become dominant in 36 locations. Conclusions: The Omicron variant has much higher transmission potential compared with the Delta variant, and the Delta variant has higher transmission potential compared with the pre-Delta VOCs.

Evaluation of Effectiveness of Global COVID-19 Vaccination Campaign.

To model estimated deaths averted by COVID-19 vaccines, we used state-of-the-art mathematical modeling, likelihood-based inference, and reported COVID-19 death and vaccination data. We estimated that >1.5 million deaths were averted in 12 countries. Our model can help assess effectiveness of the vaccination program, which is crucial for curbing the COVID-19 pandemic.

A machine learning method for estimating the probability of presence using presence-background data.

Estimating the prevalence or the absolute probability of the presence of a species from presence-background data has become a controversial topic in species distribution modelling. In this paper, we propose a new method by combining both statistics and machine learning algorithms that helps overcome some of the known existing problems. We have also revisited the popular but highly controversial Lele and Keim (LK) method by evaluating its performance and assessing the RSPF condition it relies on. Simulations show that the LK method with the RSPF assumptions would render fragile estimation/prediction of the desired probabilities. Rather, we propose the local knowledge condition, which relaxes the predetermined population prevalence condition that has so often been used in much of the existing literature. Simulations demonstrate the performance of the new method utilizing the local knowledge assumption to successfully estimate the probability of presence. The local knowledge extends the local certainty or the prototypical presence location assumption, and has significant implications for demonstrating the necessary condition for identifying absolute (rather than relative) probability of presence from presence background without absence data in species distribution modelling.

Modelling COVID-19 vaccine breakthrough infections in highly vaccinated Israel-The effects of waning immunity and third vaccination dose.

In August 2021, a major wave of the SARS-CoV-2 Delta variant erupted in the highly vaccinated population of Israel. The transmission advantage of the Delta variant enabled it to replace the Alpha variant in approximately two months. The outbreak led to an unexpectedly large proportion of breakthrough infections (BTI)-a phenomenon that received worldwide attention. Most of the Israeli population, especially those aged 60+, received their second dose of the vaccination four months before the invasion of the Delta variant. Hence, either the vaccine induced immunity dropped significantly or the Delta variant possesses immunity escaping abilities, or both. In this work, we model data obtained from the Israeli Ministry of Health, to help understand the epidemiological factors involved in the outbreak. We propose a mathematical model that captures a multitude of factors, including age structure, the time varying vaccine efficacy, time varying transmission rate, BTIs, reduced susceptibility and infectivity of vaccinated individuals, protection duration of the vaccine induced immunity, and the vaccine distribution. We fitted our model to COVID-19 cases among the vaccinated and unvaccinated, for <60 and 60+ age groups, and quantified the transmission rate, the vaccine efficacy over time and the impact of the third dose booster vaccine. The peak transmission rate of the Delta variant was found to be 2.14 times higher than that of the Alpha variant. The two-dose vaccine efficacy against infection dropped significantly from >90% to ~40% over 6 months. We further performed model simulations and quantified counterfactual scenarios examining what would happen if the booster had not been rolled out. We estimated that approximately 4.03 million infective cases (95%CI 3.19, 4.86) were prevented by vaccination overall, and 1.22 million infective cases (95%CI 0.89, 1.62) averted by the booster.

Percolation of heterogeneous flows uncovers the bottlenecks of infrastructure networks.

Whether it be the passengers' mobility demand in transportation systems, or the consumers' energy demand in power grids, the primary purpose of many infrastructure networks is to best serve this flow demand. In reality, the volume of flow demand fluctuates unevenly across complex networks while simultaneously being hindered by some form of congestion or overload. Nevertheless, there is little known about how the heterogeneity of flow demand influences the network flow dynamics under congestion. To explore this, we introduce a percolation-based network analysis framework underpinned by flow heterogeneity. Thereby, we theoretically identify bottleneck links with guaranteed decisive impact on how flows are passed through the network. The effectiveness of the framework is demonstrated on large-scale real transportation networks, where mitigating the congestion on a small fraction of the links identified as bottlenecks results in a significant network improvement.

Post-lockdown abatement of COVID-19 by fast periodic switching.

COVID-19 abatement strategies have risks and uncertainties which could lead to repeating waves of infection. We show-as proof of concept grounded on rigorous mathematical evidence-that periodic, high-frequency alternation of into, and out-of, lockdown effectively mitigates second-wave effects, while allowing continued, albeit reduced, economic activity. Periodicity confers (i) predictability, which is essential for economic sustainability, and (ii) robustness, since lockdown periods are not activated by uncertain measurements over short time scales. In turn-while not eliminating the virus-this fast switching policy is sustainable over time, and it mitigates the infection until a vaccine or treatment becomes available, while alleviating the social costs associated with long lockdowns. Typically, the policy might be in the form of 1-day of work followed by 6-days of lockdown every week (or perhaps 2 days working, 5 days off) and it can be modified at a slow-rate based on measurements filtered over longer time scales. Our results highlight the potential efficacy of high frequency switching interventions in post lockdown mitigation. All code is available on Github at https://github.com/V4p1d/FPSP_Covid19. A software tool has also been developed so that interested parties can explore the proof-of-concept system.

Kemeny-based testing for COVID-19.

Testing, tracking and tracing abilities have been identified as pivotal in helping countries to safely reopen activities after the first wave of the COVID-19 virus. Contact tracing apps give the unprecedented possibility to reconstruct graphs of daily contacts, so the question is: who should be tested? As human contact networks are known to exhibit community structure, in this paper we show that the Kemeny constant of a graph can be used to identify and analyze bridges between communities in a graph. Our 'Kemeny indicator' is the value of the Kemeny constant in the new graph that is obtained when a node is removed from the original graph. We show that testing individuals who are associated with large values of the Kemeny indicator can help in efficiently intercepting new virus outbreaks, when they are still in their early stage. Extensive simulations provide promising results in early identification and in blocking the possible 'super-spreaders' links that transmit disease between different communities.

Extraordinary curtailment of massive typhus epidemic in the Warsaw Ghetto.

The highly dependent interplay of disease, famine, war, and society is examined based on an extreme period during World War II. Using mathematical modeling, we reassess events during the Holocaust that led to the liquidation of the Warsaw Ghetto (1941-1942), with the eventual goal of deliberately killing ~450,000, mostly Jewish residents, many through widespread starvation and a large-scale typhus epidemic. The Nazis justified genocide supposedly to control the spread of disease. This exemplifies humanity's ability to turn upon itself, based on racially guided epidemiological principles, merely because of the appearance of a bacterium. Deadly disease and starvation dynamics are explored using modeling and the maths of food ration cards. Strangely, the epidemic was curtailed and was brought to a sudden halt before winter, when typhus normally accelerates. A far more massive epidemic outbreak was prevented through the antiepidemic efforts by the often considered incompetent and corrupt ghetto leadership and the Herculean efforts of ghetto doctors.

Coherence of dengue incidence and climate in the wet and dry zones of Sri Lanka.

We studied the dynamics of dengue disease in two epidemic regions in Sri Lanka, the densely populated Colombo district representing the wet zone and the relatively less populated Batticaloa district representing the dry zone. Regional differences in disease dynamics were analysed against regional weather factors. Wavelets, Granger causality and regression methods were used. The difference between the dynamical features of these two regions may be explained by the differences in the climatic characteristics of the two regions. Wavelet analysis revealed that Colombo dengue incidence has 6 months periodicity while Batticaloa dengue incidence has 1 year periodicity. This is well explained by the dominant 6 months periodicity in Colombo rainfall and 1 year periodicity in Batticaloa rainfall. The association between dengue incidence and temperature was negative in dry Batticaloa and was insignificant in wet Colombo. Granger causality results indicated that rainfall, rainy days, relative humidity and wind speed can be used to predict Colombo dengue incidence while only rainfall and relative humidity were significant in Batticaloa. Negative binomial and linear regression models were used to identify the weather variables which best explain the variations in dengue incidence. Most recent available incidence data performed as best explanatory variables, outweighing the importance of past weather data. Therefore we recommend the health authorities to closely monitor the number of cases and to streamline recording procedures so that most recent data are available for early detection of epidemics. We also noted that epidemic responses to weather changes appear quickly in densely populated Colombo compared to less populated Batticaloa. The past dengue incidence and weather variables explain the dengue incidence better in Batticaloa than in Colombo and thus other exogenous factors such as population density and human mobility may be affecting Colombo dengue incidence.

Imitation dynamics in the mitigation of the novel coronavirus disease (COVID-19) outbreak in Wuhan, China from 2019 to 2020.

BACKGROUND: The coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China on December 2019 in patients presenting with atypical pneumonia. Although 'city-lockdown' policy reduced the spatial spreading of the COVID-19, the city-level outbreaks within each city remain a major concern to be addressed. The local or regional level disease control mainly depends on individuals self-administered infection prevention actions. The contradiction between choice of taking infection prevention actions or not makes the elimination difficult under a voluntary acting scheme, and represents a clash between the optimal choice of action for the individual interest and group interests. METHODS: We develop a compartmental epidemic model based on the classic susceptible-exposed-infectious-recovered model and use this to fit the data. Behavioral imitation through a game theoretical decision-making process is incorporated to study and project the dynamics of the COVID-19 outbreak in Wuhan, China. By varying the key model parameters, we explore the probable course of the outbreak in terms of size and timing under several public interventions in improving public awareness and sensitivity to the infection risk as well as their potential impact. RESULTS: We estimate the basic reproduction number, R 0, to be 2.5 (95% CI: 2.4-2.7). Under the current most realistic setting, we estimate the peak size at 0.28 (95% CI: 0.24-0.32) infections per 1,000 population. In Wuhan, the final size of the outbreak is likely to infect 1.35% (95% CI: 1.00-2.12%) of the population. The outbreak will be most likely to peak in the first half of February and drop to daily incidences lower than 10 in June 2020. Increasing sensitivity to take infection prevention actions and the effectiveness of infection prevention measures are likely to mitigate the COVID-19 outbreak in Wuhan. CONCLUSIONS: Through an imitating social learning process, individual-level behavioral change on taking infection prevention actions have the potentials to significantly reduce the COVID-19 outbreak in terms of size and timing at city-level. Timely and substantially resources and supports for improving the willingness-to-act and conducts of self-administered infection prevention actions are recommended to reduce to the COVID-19 associated risks.

The stability of mutualism.

Positive interactions are observed at high frequencies in nearly all living systems, ranging from human and animal societies down to the scale of microbial organisms. However, historically, detailed ecological studies of mutualism have been relatively unrepresented. Moreover, while ecologists have long portrayed competition as a stabilizing process, mutualism is often deemed destabilizing. Recently, several key modelling studies have applied random matrix methods, and have further corroborated the instability of mutualism. Here, I reassess these findings by factoring in species densities into the "community matrix," a practice which has almost always been ignored in random matrix analyses. With this modification, mutualistic interactions are found to boost equilibrium population densities and stabilize communities by increasing their resilience. By taking into account transient dynamics after a strong population perturbation, it is found that mutualists have the ability to pull up communities by their bootstraps when species are dangerously depressed in numbers.

New estimates of the Zika virus epidemic attack rate in Northeastern Brazil from 2015 to 2016: A modelling analysis based on Guillain-Barré Syndrome (GBS) surveillance data.

BACKGROUND: Between January 2015 and August 2016, two epidemic waves of Zika virus (ZIKV) disease swept the Northeastern (NE) region of Brazil. As a result, two waves of Guillain-Barré Syndrome (GBS) were observed concurrently. The mandatory reporting of ZIKV disease began region-wide in February 2016, and it is believed that ZIKV cases were significantly under-reported before that. The changing reporting rate has made it difficult to estimate the ZIKV infection attack rate, and studies in the literature vary widely from 17% to > 50%. The same applies to other key epidemiological parameters. In contrast, the diagnosis and reporting of GBS cases were reasonably reliable given the severity and easy recognition of the disease symptoms. In this paper, we aim to estimate the real number of ZIKV cases (i.e., the infection attack rate) and their dynamics in time, by scaling up from GBS surveillance data in NE Brazil. METHODOLOGY: A mathematical compartmental model is constructed that makes it possible to infer the true epidemic dynamics of ZIKV cases based on surveillance data of excess GBS cases. The model includes the possibility that asymptomatic ZIKV cases are infectious. The model is fitted to the GBS surveillance data and the key epidemiological parameters are inferred by using a plug-and-play likelihood-based estimation. We make use of regional weather data to determine possible climate-driven impacts on the reproductive number [Formula: see text], and to infer the true ZIKV epidemic dynamics. FINDINGS AND CONCLUSIONS: The GBS surveillance data can be used to study ZIKV epidemics and may be appropriate when ZIKV reporting rates are not well understood. The overall infection attack rate (IAR) of ZIKV is estimated to be 24.1% (95% confidence interval: 17.1%-29.3%) of the population. By examining various asymptomatic scenarios, the IAR is likely to be lower than 33% over the two ZIKV waves. The risk rate from symptomatic ZIKV infection to develop GBS was estimated as ρ = 0.0061% (95% CI: 0.0050%-0.0086%) which is significantly less than current estimates. We found a positive association between local temperature and the basic reproduction number, [Formula: see text]. Our analysis revealed that asymptomatic infections affect the estimation of ZIKV epidemics and need to also be carefully considered in related modelling studies. According to the estimated effective reproduction number and population wide susceptibility, we comment that a ZIKV outbreak would be unlikely in NE Brazil in the near future.

Spatiotemporal patterns of dengue outbreaks in Sri Lanka.

Background: Dengue occurs epidemically in Sri Lanka and every year, when the monsoon season begins, health authorities warn on rising numbers of dengue cases. The popular belief is that dengue epidemics are driven by the two monsoons which feed different parts of the country over different time periods. We analysed the time series of weekly dengue cases in all districts of Sri Lanka from 2007 to 2019 to identify the spatiotemporal patterns of dengue outbreaks and to explain how they are associated with the climatic, geographic and demographic variations around the country.Methods: We used time-series plots, statistical measures such a community-wide synchrony and Kendall-W and a time-varying graph method to understand the spatiotemporal patterns and links.Results and conclusions: The southwest wet zone and surrounding areas which receive rainfall in all four seasons usually experience two epidemic waves per year. The northern and eastern coastal region in the dry zone which receives rainfall in only two seasons experiences one epidemic wave per year. The wet zone is a highly synchronised epidemic unit while the northern and eastern districts have more independent epidemic patterns. The epidemic synchrony in the wet zone may be associated with the frequent mobility of people in and out of the wet zone hot spot Colombo. The overall epidemic pattern in Sri Lanka is not a sole outcome of the two monsoons but the regional epidemic patterns are collectively shaped by monsoon an inter-monsoon rains, human mobility, geographical proximity and other climate and topographical factors.

High-resolution inference of genetic relationships among Jewish populations.

Recent studies have used genome-wide single-nucleotide polymorphisms (SNPs) to investigate relationships among various Jewish populations and their non-Jewish historical neighbors, often focusing on small subsets of populations from a limited geographic range or relatively small samples within populations. Here, building on the significant progress that has emerged from genomic SNP studies in the placement of Jewish populations in relation to non-Jewish populations, we focus on population structure among Jewish populations. In particular, we examine Jewish population-genetic structure in samples that span much of the historical range of Jewish populations in Europe, the Middle East, North Africa, and South Asia. Combining 429 newly genotyped samples from 29 Jewish and 3 non-Jewish populations with previously reported genotypes on Jewish and non-Jewish populations, we investigate variation in 2789 individuals from 114 populations at 486,592 genome-wide autosomal SNPs. Using multidimensional scaling analysis, unsupervised model-based clustering, and population trees, we find that, genetically, most Jewish samples fall into four major clusters that largely represent four culturally defined groupings, namely the Ashkenazi, Mizrahi, North African, and Sephardi subdivisions of the Jewish population. We detect high-resolution population structure, including separation of the Ashkenazi and Sephardi groups and distinctions among populations within the Mizrahi and North African groups. Our results refine knowledge of Jewish population-genetic structure and contribute to a growing understanding of the distinctive genetic ancestry evident in closely related but historically separate Jewish communities.

Difficulties in benchmarking ecological null models: an assessment of current methods.

Identifying species interactions and detecting when ecological communities are structured by them is an important problem in ecology and biogeography. Ecologists have developed specialized statistical hypothesis tests to detect patterns indicative of community-wide processes in their field data. In this respect, null model approaches have proved particularly popular. The freedom allowed in choosing the null model and statistic to construct a hypothesis test leads to a proliferation of possible hypothesis tests from which ecologists can choose to detect these processes. Here, we point out some serious shortcomings of a popular approach to choosing the best hypothesis for the ecological problem at hand that involves benchmarking different hypothesis tests by assessing their performance on artificially constructed data sets. Terminological errors concerning the use of Type I and Type II errors that underlie these approaches are discussed. We argue that the key benchmarking methods proposed in the literature are not a sound guide for selecting null hypothesis tests, and further, that there is no simple way to benchmark null hypothesis tests. Surprisingly, the basic problems identified here do not appear to have been addressed previously, and these methods are still being used to develop and test new null models and summary statistics, from quantifying community structure (e.g., nestedness and modularity) to analyzing ecological networks.