The role of socio-economic disparities in the relative success of SARS-CoV-2 variants in New York City in early 2021 (preprint)

Background: Socio-economic disparities were associated with disproportionate viral incidence between neighborhoods of New York City (NYC) during the first wave of SARS-CoV-2. We investigated how these disparities affected the co-circulation SARS-CoV-2 variants during the second wave in NYC. Methods: We tested for correlation between the prevalence, in late 2020/early 2021, of Alpha, Iota, Iota with E484K mutation (Iota-E484K), and B.1-like genomes and pre-existing immunity (seropositivity) in NYC neighborhoods. In the context of varying seroprevalence we described socio-economic profiles of neighborhoods and performed migration and lineage persistence analyses using a Bayesian phylogeographical framework. Findings: Seropositivity was greater in areas with high poverty and a larger proportion of Black and Hispanic or Latino residents. Seropositivity was positively correlated with the proportion of Iota-E484K and Iota genomes, and negatively correlated with the proportion of Alpha and B.1-like genomes. The proportion of persisting Alpha lineages declined over time in locations with high seroprevalence, whereas the proportion of persisting Iota-E484K lineages remained the same in high seroprevalence areas. Interpretation: During the second wave, the geographic variation of standing immunity, due to disproportionate disease burden during the first wave of SARS-CoV-2 in NYC, allowed for the immune evasive Iota-E484K variant, but not the more transmissible Alpha variant, to circulate in locations with high pre-existing immunity. Funding: We acknowledge funding from the National Institutes of Health and the Centers for Disease Control and Prevention.

Intracellular "in silico microscopes"-fully 3D spatial Hepatitis C virus replication model simulations

Virus pandemics and endemics cause enormous pain and economic, political, and social costs and turmoil. While the Covid19 pandemics induced obvious damages, the "silent" Hepatitis C virus (HCV) infection induced liver damages are the main reason for liver transplantations. HCV-generated virus genome replication factories are housed within virus-induced intracellular structures termed membranous webs (MW) which are derived from the Endoplasmatic Reticulum (ER). Up to now, very advanced experimental data such as highly spatially resolved fuorescence and electron-tomography data often do not enter computational HCV viral RNA (vRNA) cycle models. Based upon difusion-reaction partial differential equation (PDE) models, we are developing fully 3D resolved "in silico microscopes" to mirror in vitro / in vivo experiments of the intracellular vRNA cycle dynamics. Our first models described the major components (vRNA, non-structural viral proteins-NSPs-and a host factor). The next steps incorporated additional parameters: Different aggregate states of vRNA and NSPs, and population dynamics inspired difusion and reaction co-Effcients instead of multilinear ones. Our work in progress framework presently is merging effects restricted to 2D manifold surface grids (e.g. ER surface, NSP difusion) with others occurring in 3D volume meshes (e.g. cytosol, host factor supply). We estimate and incorporate realistic parameters such as NSP difusion constants. The simulations are performed upon experimental data based reconstructed cell geometries and help understanding the relation of form and function of virus replication. In the long run, our framework might help to facilitate the systematic development of Effcient direct antiviral agents and vaccines.

Rethinking integrated service delivery for malaria

Despite worldwide efforts and much progress toward malaria control, declines in malaria morbidity and mortality have hit a plateau. While many nations achieved significant malaria suppression or even elimination, success has been uneven, and other nations have made little headway—or even lost ground in this battle. These alarming trends threaten to derail the attainment of global targets for malaria control. Among the challenges impeding success in malaria reduction, many strategies center malaria as a set of technical problems in commodity development and delivery. Yet, this narrow perspective overlooks the importance of strong health systems and robust healthcare delivery. This paper argues that strategies that move the needle on health services and behaviors offer a significant opportunity to achieve malaria control through a comprehensive approach that integrates malaria with broader health services efforts. Indeed, malaria may serve as the thread that weaves integrated service delivery into a path forward for universal health coverage. Using key themes identified by the "Rethinking Malaria in the Context of COVID-19" effort through engagement with key stakeholders, we provide recommendations for pursuing integrated service delivery that can advance malaria control via strengthening health systems, increasing visibility and use of high-quality data at all levels, centering issues of equity, promoting research and innovation for new tools, expanding knowledge on effective implementation strategies for interventions, making the case for investing in malaria among stakeholders, and engaging impacted communities and nations.

Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics (preprint)

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of SARS-CoV-2 lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of 'local' when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

Global disparities in SARS-CoV-2 genomic surveillance.

Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity.

Common mental disorders during the COVID-19 pandemic in Hong Kong: Age-related differences and implications for dementia risk

Background The COVID-19 pandemic has imposed a profound negative impact on the mental health and wellbeing of societies and individuals worldwide. Older adults may be more vulnerable to the mental health effects of the pandemic, either directly from the infection itself or indirectly through the preventive measures. However, the existing literature on mental health in the older age groups has not been consistent so far. The aim of this study was therefore to assess the prevalence of common mental disorders (CMD;including depression and anxiety disorders) given their association with dementia risk, and to further examine age-related differences between older (≥60 years old) and younger (18–59 years old) adult's psychological status during the COVID-19 pandemic. Method This was a secondary analysis of a cross-sectional survey-study conducted during the second wave of COVID-19 pandemic in Hong Kong. The survey was disseminated through different social media platforms to the general population and included sociodemographic questions, self-reported physical health, and previous encounter with SARS or COVID-19. CMD was the primary outcome and was assessed using the 6-item Kessler Scale. A total of 1030 adults fulfilled inclusion criteria. Results The prevalence of CMD during the pandemic was 16.1%. Compared to younger adults, older adults were significantly less likely to have a CMD (unadjusted OR = 0.07, 95% CI = 0.02–0.30, p < 0.001), with 18.1% of younger adults having CMD compared to 1.6% in the older cohort. Age differences remained significant after controlling for sociodemographic factors, physical health, and previous encounter with SARS or COVID-19 (adjusted OR = 0.12, 95% CI = 0.02–0.57, p = 0.008). Conclusion Common mental disorders are highly prevalent during the COVID-19 pandemic in Hong Kong, though older adults appeared to be less affected mentally. Present findings highlight the urgent need to implement measures and strategies to mitigate the mental health problems, with particular attention to the younger cohort. Given their association with higher dementia risk, early detection and treatment of depression and anxiety disorders will be of critical importance in providing some relief to the already pressurized dementia burden in the longer term.

Rethinking integrated service delivery for malaria.

Despite worldwide efforts and much progress toward malaria control, declines in malaria morbidity and mortality have hit a plateau. While many nations achieved significant malaria suppression or even elimination, success has been uneven, and other nations have made little headway-or even lost ground in this battle. These alarming trends threaten to derail the attainment of global targets for malaria control. Among the challenges impeding success in malaria reduction, many strategies center malaria as a set of technical problems in commodity development and delivery. Yet, this narrow perspective overlooks the importance of strong health systems and robust healthcare delivery. This paper argues that strategies that move the needle on health services and behaviors offer a significant opportunity to achieve malaria control through a comprehensive approach that integrates malaria with broader health services efforts. Indeed, malaria may serve as the thread that weaves integrated service delivery into a path forward for universal health coverage. Using key themes identified by the "Rethinking Malaria in the Context of COVID-19" effort through engagement with key stakeholders, we provide recommendations for pursuing integrated service delivery that can advance malaria control via strengthening health systems, increasing visibility and use of high-quality data at all levels, centering issues of equity, promoting research and innovation for new tools, expanding knowledge on effective implementation strategies for interventions, making the case for investing in malaria among stakeholders, and engaging impacted communities and nations.

Scalable Bayesian phylogenetics.

Recent advances in Bayesian phylogenetics offer substantial computational savings to accommodate increased genomic sampling that challenges traditional inference methods. In this review, we begin with a brief summary of the Bayesian phylogenetic framework, and then conceptualize a variety of methods to improve posterior approximations via Markov chain Monte Carlo (MCMC) sampling. Specifically, we discuss methods to improve the speed of likelihood calculations, reduce MCMC burn-in, and generate better MCMC proposals. We apply several of these techniques to study the evolution of HIV virulence along a 1536-tip phylogeny and estimate the internal node heights of a 1000-tip SARS-CoV-2 phylogenetic tree in order to illustrate the speed-up of such analyses using current state-of-the-art approaches. We conclude our review with a discussion of promising alternatives to MCMC that approximate the phylogenetic posterior. This article is part of a discussion meeting issue 'Genomic population structures of microbial pathogens'.

Introduction and Establishment of SARS-CoV-2 Gamma Variant in New York City in Early 2021.

BACKGROUND: Monitoring the emergence and spread of SARS-CoV-2 variants is an important public health objective. We investigated how the Gamma variant was established in New York City (NYC) in early 2021 in the presence of travel restrictions that aimed to prevent viral spread from Brazil, the country where the variant was first identified. METHODS: We performed phylogeographic analysis on 15,967 Gamma sequences sampled between March 10th through May 1st, 2021, to identify geographic sources of Gamma lineages introduced into NYC. We identified locally circulating Gamma transmission clusters and inferred the timing of their establishment in NYC. RESULTS: We identified 16 phylogenetically-distinct Gamma clusters established in NYC (cluster sizes ranged 2-108 genomes); most of them were introduced from Florida and Illinois and only one directly from Brazil. By the time the first Gamma case was reported by genomic surveillance in NYC on March 10th, the majority (57%) of circulating Gamma lineages had already been established in the city for at least two weeks. CONCLUSIONS: Although travel from Brazil to the US was restricted from May 2020 through the end of the study period, this restriction did not prevent Gamma from becoming established in NYC as most introductions occurred from domestic locations.

Do people with mental health problems have lower adherence to precautionary measures in COVID-19 pandemic? A cross-sectional observational study in Hong Kong

ObjectivesMental health problems are prevalent during the COVID-19 pandemic, but their effect on adherence to precautionary measures is not well understood. Given that psychological morbidities are associated with lower treatment adherence, and that precautionary measures are important in containing the spread of COVID-19, this study aims to determine if people with mental health problems have lower adherence to precautionary measures against COVID-19.DesignWe conducted a cross-sectional territory-wide online survey between 17 June and 31 July 2020 during the COVID-19 pandemic. Clinically significant mental health problems, adherence to precautionary behaviours, and confounding factors such as sociodemographic factors and self-reported physical health were assessed.SettingThe link to the questionnaire was disseminated to the general population in all 18 districts of Hong Kong using various social media platforms.Participants1036 individuals completed the survey. Of them, 1030 met the inclusion criteria of being adult Hong Kong residents.Primary outcomeAdherence to precautionary measures against COVID-19, including wearing face mask, frequent handwashing, household disinfection, social distancing, minimising unnecessary travel, and stocking up on food and daily essentials.ResultsOf the 1030 participants, 166 (16.1%) had clinically significant mental health problems. Interestingly, they were more likely to stock up on food and daily essentials during the pandemic (7 (4.2%) vs 15 (1.7%), p=0.04;unadjusted OR=2.49, 95% CI=1.00 to 6.21, p<0.05) and had a lesser tendency to stop social distancing even if the pandemic subsides (86 (51.8%) vs 513 (59.4%), p=0.07;unadjusted OR=0.74, 95% CI=0.53 to 1.03, p=0.07). The latter association remained significant after adjusting for the confounding factors (adjusted OR=0.68, 95% CI=0.48 to 0.96, p=0.03).ConclusionsContrary to our hypothesis, people who are mentally unwell might go beyond the recommended precautionary measures. Our findings highlight the need to identify mental health problems and provide care and support for those who might go too far with precautionary measures.Trial registration numberChiCTR 2000033936.

Introduction and Establishment of SARS-CoV-2 Gamma Variant in New York City in Early 2021 (preprint)

Background. Monitoring the emergence and spread of SARS-CoV-2 variants is an important public health objective. Travel restrictions, aimed to prevent viral spread, have major economic consequences and unclear effectiveness despite considerable research. We investigated the introduction and establishment of the Gamma variant in New York City (NYC) in 2021. Methods. We performed phylogeographic analysis on 15,967 Gamma sequences available on GISAID and sampled between March 10th through May 1st, 2021, to identify geographic sources of Gamma lineages introduced into NYC. We identified locally circulating Gamma transmission clusters and inferred the timing of their establishment in NYC. Findings. We identified 16 phylogenetically-distinct Gamma clusters established in NYC (cluster sizes ranged 2-108 genomes). Most of the NYC clusters were introduced from Florida and Illinois; only one was introduced from outside the United States (US). By the time the first Gamma case was reported by genomic surveillance in NYC on March 10th, the majority (57%) of circulating Gamma lineages had already been established in the city for at least two weeks. Interpretation. Despite the expansion of SARS-CoV-2 genomic surveillance in NYC, there was a substantial gap between Gamma variant introduction and establishment in January/February 2021, and its identification by genomic surveillance in March 2021. Although travel from Brazil to the US was restricted from May 2020 through the end of the study period, this restriction did not prevent Gamma from becoming established in NYC as most introductions occurred from domestic locations.

Global disparities in SARS-CoV-2 genomic surveillance (preprint)

Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness. One-Sentence SummarySocioeconomic inequalities impacted the SARS-CoV-2 genomic surveillance, and undermined the global pandemic preparedness.

COVID-19 shifts mortality salience, activities, and values in the United States: Big data analysis of online adaptation.

What is the effect of a life-threatening pandemic at the societal level? An expanded Theory of Social Change, Cultural Evolution, and Human Development predicts that, during a period of increasing survival threat and decreasing prosperity, humans will shift toward the psychology and behavior typical of the small-scale, collectivistic, and rural subsistence ecologies in which we evolved. In particular, subjective mortality salience, engagement in subsistence activities, and collectivism will all increase, while the aspiration to be wealthy will decrease. Because coronavirus has forced unprecedented proportions of human activity online, we tested hypotheses derived from the theory by analyzing big data samples for 70 days before and 70 days after the coronavirus pandemic stimulated President Trump to declare a national emergency. Google searches were used for an exploratory study; the exploratory study was followed by three independent replications on Twitter, internet forums, and blogs. Across all four internet platforms, terms related to subjective mortality salience, engagement in subsistence activities, and collectivism showed massive increases. These findings, coupled with prior research testing this theory, indicate that humans may have an evolutionarily conditioned response to the level of death and availability of material resources in society. More specifically, humans may shift their behavior and psychology toward that found in subsistence ecologies under conditions of high mortality and low prosperity or, conversely, toward behavior and psychology found in modern commercial ecologies under conditions of low mortality and high prosperity.

COVID-19 shifts mortality salience, activities, and values in the United States: Big data analysis of online adaptation

Abstract What is the effect of a life-threatening pandemic at the societal level? An expanded Theory of Social Change, Cultural Evolution, and Human Development predicts that, during a period of increasing survival threat and decreasing prosperity, humans will shift toward the psychology and behavior typical of the small-scale, collectivistic, and rural subsistence ecologies in which we evolved. In particular, subjective mortality salience, engagement in subsistence activities, and collectivism will all increase, while the aspiration to be wealthy will decrease. Because coronavirus has forced unprecedented proportions of human activity online, we tested hypotheses derived from the theory by analyzing big data samples for 70?days before and 70?days after the coronavirus pandemic stimulated President Trump to declare a national emergency. Google searches were used for an exploratory study;the exploratory study was followed by three independent replications on Twitter, internet forums, and blogs. Across all four internet platforms, terms related to subjective mortality salience, engagement in subsistence activities, and collectivism showed massive increases. These findings, coupled with prior research testing this theory, indicate that humans may have an evolutionarily conditioned response to the level of death and availability of material resources in society. More specifically, humans may shift their behavior and psychology toward that found in subsistence ecologies under conditions of high mortality and low prosperity or, conversely, toward behavior and psychology found in modern commercial ecologies under conditions of low mortality and high prosperity.