scholarly journals Controlling long-term SARS-CoV-2 infections can slow viral evolution and reduce the risk of treatment failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Debra Van Egeren ◽  
Alexander Novokhodko ◽  
Madison Stoddard ◽  
Uyen Tran ◽  
Bruce Zetter ◽  
...  
Keyword(s):  
Viral Evolution ◽  
Herd Immunity ◽  
Point Mutations ◽  
Population Level ◽  
Multiple Point ◽  
Evolutionary Modeling ◽  
Modeling Framework ◽  
Stochastic Events ◽  
Risk Of Treatment

AbstractThe rapid emergence and expansion of novel SARS-CoV-2 variants threatens our ability to achieve herd immunity for COVID-19. These novel SARS-CoV-2 variants often harbor multiple point mutations, conferring one or more evolutionarily advantageous traits, such as increased transmissibility, immune evasion and longer infection duration. In a number of cases, variant emergence has been linked to long-term infections in individuals who were either immunocompromised or treated with convalescent plasma. In this paper, we used a stochastic evolutionary modeling framework to explore the emergence of fitter variants of SARS-CoV-2 during long-term infections. We found that increased viral load and infection duration favor emergence of such variants. While the overall probability of emergence and subsequent transmission from any given infection is low, on a population level these events occur fairly frequently. Targeting these low-probability stochastic events that lead to the establishment of novel advantageous viral variants might allow us to slow the rate at which they emerge in the patient population, and prevent them from spreading deterministically due to natural selection. Our work thus suggests practical ways to achieve control of long-term SARS-CoV-2 infections, which will be critical for slowing the rate of viral evolution.

scholarly journals Controlling long-term SARS-CoV-2 infections is important for slowing viral evolution

2021 ◽  
Author(s):  
Debra Van Egeren ◽  
Alexander Novokhodko ◽  
Madison Stoddard ◽  
Uyen Tran ◽  
Diane Joseph-McCarthy ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Viral Evolution ◽  
Herd Immunity ◽  
Point Mutations ◽  
Multiple Point ◽  
Random Events ◽  
Evolutionary Advantage ◽  
Low Probability ◽  
Rapid Emergence

The rapid emergence and expansion of novel SARS-CoV-2 variants is an unpleasant surprise that threatens our ability to achieve herd immunity for COVID-19. These fitter SARS- CoV-2 variants often harbor multiple point mutations, conferring one or more traits that provide an evolutionary advantage, such as increased transmissibility, immune evasion and longer infection duration. In a number of cases, variant emergence has been linked to long-term infections in individuals who were either immunocompromised or treated with convalescent plasma. In this paper, we explore the mechanism by which fitter variants of SARS-CoV-2 arise during long-term infections using a mathematical model of viral evolution and identify means by which this evolution can be slowed. While viral load and infection duration play a strong role in favoring the emergence of such variants, the overall probability of emergence and subsequent transmission from any given infection is low, suggesting that viral variant emergence and establishment is a product of random chance. To the extent that luck plays a role in favoring the emergence of novel viral variants with an evolutionary advantage, targeting these low-probability random events might allow us to tip the balance of fortune away from these advantageous variants and prevent them from being established in the population.

Idiopathic venous thrombosis

2006 ◽  
Vol 26 (01) ◽  
pp. 52-54 ◽  
Author(s):  
P. A. Kyrle
Keyword(s):  
Chronic Disease ◽  
Venous Thrombosis ◽  
Vitamin K ◽  
Clinical Benefit ◽  
Plasma Levels ◽  
Vitamin K Antagonists ◽  
Antithrombin Deficiency ◽  
Optimal Duration ◽  
Risk Of Treatment

SummaryVenous thrombosis is a chronic disease with a recurrence rate of approximately 30% within 5-8 years. The optimal duration of secondary thromboprophylaxis in these patients entails balancing the risk of recurrence against the risk of treatment-associated bleeding. There is agreement that patients with a first idiopathic venous thrombosis should receive vitamin K antagonists for at least 3-6 months. Convincing trials showing a clinical benefit in terms of morbidity or mortality with respect to expansion of anticoagulation beyond 6 months are lacking. Nevertheless, some subgroups of patients with venous thrombosis may benefit from indefinite anticoagulation. Thus, patients with antithrombin deficiency, combined or homozygous defects, more than one unprovoked episode of thrombosis, the lupus anticoagulant or high factor VIII plasma levels are good candidates for long-term prevention.

scholarly journals Are We Paving the Way to Dig Out of the “Pandemic Hole”? A Narrative Review on SARS-CoV-2 Vaccination: From Animal Models to Human Immunization

2021 ◽  
Vol 9 (3) ◽  
pp. 53
Author(s):  
Giuseppe Tardiolo ◽  
Pina Brianti ◽  
Daniela Sapienza ◽  
Pia dell’Utri ◽  
Viviane Di Dio ◽  
...  
Keyword(s):  
Animal Models ◽  
Viral Vector ◽  
Herd Immunity ◽  
Population Level ◽  
Narrative Review ◽  
Therapeutic Interventions ◽  
Preclinical Research ◽  
Inactivated Vaccines ◽  
Preclinical And Clinical Studies ◽  
Social Upheaval

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.

scholarly journals Responses of Vertebrate Wildlife to Oil and Natural Gas Development: Patterns and Frontiers

2021 ◽  
Author(s):  
A. D. Chalfoun
Keyword(s):  
Natural Gas ◽  
Anthropogenic Activities ◽  
Spatial Scales ◽  
Habitat Type ◽  
Population Level ◽  
Low Frequencies ◽  
Natural Gas Development ◽  
The Usa ◽  
Oil And Natural Gas

Abstract Purpose of Review Anthropogenic activities can lead to the loss, fragmentation, and alteration of wildlife habitats. I reviewed the recent literature (2014–2019) focused on the responses of avian, mammalian, and herpetofaunal species to oil and natural gas development, a widespread and still-expanding land use worldwide. My primary goals were to identify any generalities in species’ responses to development and summarize remaining gaps in knowledge. To do so, I evaluated the directionality of a wide variety of responses in relation to taxon, location, development type, development metric, habitat type, and spatiotemporal aspects. Recent Findings Studies (n = 70) were restricted to the USA and Canada, and taxonomically biased towards birds and mammals. Longer studies, but not those incorporating multiple spatial scales, were more likely to detect significant responses. Negative responses of all types were present in relatively low frequencies across all taxa, locations, development types, and development metrics but were context-dependent. The directionality of responses by the same species often varied across studies or development metrics. Summary The state of knowledge about wildlife responses to oil and natural gas development has developed considerably, though many biases and gaps remain. Studies outside of North America and that focus on herpetofauna are lacking. Tests of mechanistic hypotheses for effects, long-term studies, assessment of response thresholds, and experimental designs that isolate the effects of different stimuli associated with development, remain critical. Moreover, tests of the efficacy of habitat mitigation efforts have been rare. Finally, investigations of the demographic effects of development across the full annual cycle were absent for non-game species and are critical for the estimation of population-level effects.

scholarly journals Advancement in long-distance bird migration through individual plasticity in departure

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jesse R. Conklin ◽  
Simeon Lisovski ◽  
Phil F. Battley
Keyword(s):  
Bird Migration ◽  
Population Level ◽  
Breeding Site ◽  
Environmental Constraints ◽  
Adaptive Responses ◽  
Long Distance ◽  
Direct Observations ◽  
Breeding Resources ◽  
Plastic Responses

AbstractGlobally, bird migration is occurring earlier in the year, consistent with climate-related changes in breeding resources. Although often attributed to phenotypic plasticity, there is no clear demonstration of long-term population advancement in avian migration through individual plasticity. Using direct observations of bar-tailed godwits (Limosa lapponica) departing New Zealand on a 16,000-km journey to Alaska, we show that migration advanced by six days during 2008–2020, and that within-individual advancement was sufficient to explain this population-level change. However, in individuals tracked for the entire migration (50 total tracks of 36 individuals), earlier departure did not lead to earlier arrival or breeding in Alaska, due to prolonged stopovers in Asia. Moreover, changes in breeding-site phenology varied across Alaska, but were not reflected in within-population differences in advancement of migratory departure. We demonstrate that plastic responses can drive population-level changes in timing of long-distance migration, but also that behavioral and environmental constraints en route may yet limit adaptive responses to global change.

scholarly journals Extensive Evaluation of a Continental-Scale High-Resolution Hydrological Model Using Remote Sensing and Ground-Based Observations

2021 ◽  
Vol 13 (7) ◽  
pp. 1247
Author(s):  
Bowen Zhu ◽  
Xianhong Xie ◽  
Chuiyu Lu ◽  
Tianjie Lei ◽  
Yibing Wang ◽  
...  
Keyword(s):  
Remote Sensing ◽  
Hydrological Modeling ◽  
Infiltration Capacity ◽  
Modeling Framework ◽  
Large Domain ◽  
Continental Scale ◽  
Extensive Evaluation ◽  
Mean Differences ◽  
Fine Resolution

Extreme hydrologic events are getting more frequent under a changing climate, and a reliable hydrological modeling framework is important to understand their mechanism. However, existing hydrological modeling frameworks are mostly constrained to a relatively coarse resolution, unrealistic input information, and insufficient evaluations, especially for the large domain, and they are, therefore, unable to address and reconstruct many of the water-related issues (e.g., flooding and drought). In this study, a 0.0625-degree (~6 km) resolution variable infiltration capacity (VIC) model developed for China from 1970 to 2016 was extensively evaluated against remote sensing and ground-based observations. A unique feature in this modeling framework is the incorporation of new remotely sensed vegetation and soil parameter dataset. To our knowledge, this constitutes the first application of VIC with such a long-term and fine resolution over a large domain, and more importantly, with a holistic system-evaluation leveraging the best available earth data. The evaluations using in-situ observations of streamflow, evapotranspiration (ET), and soil moisture (SM) indicate a great improvement. The simulations are also consistent with satellite remote sensing products of ET and SM, because the mean differences between the VIC ET and the remote sensing ET range from −2 to 2 mm/day, and the differences for SM of the top thin layer range from −2 to 3 mm. Therefore, this continental-scale hydrological modeling framework is reliable and accurate, which can be used for various applications including extreme hydrological event detections.

scholarly journals Transformed Canine and Murine Mesenchymal Stem Cells as a Model for Sarcoma with Complex Genomics

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1126
Author(s):  
Natasja Franceschini ◽  
Bas Verbruggen ◽  
Marianna A. Tryfonidou ◽  
Alwine B. Kruisselbrink ◽  
Hans Baelde ◽  
...  
Keyword(s):  
Copy Number ◽  
Point Mutations ◽  
Comparative Approach ◽  
Cell Of Origin ◽  
Mesenchymal Tumors ◽  
Spontaneous Transformation ◽  
Exon 2 ◽  
Species Analysis ◽  
Gains And Losses

Sarcomas are rare mesenchymal tumors with a broad histological spectrum, but they can be divided into two groups based on molecular pathology: sarcomas with simple or complex genomics. Tumors with complex genomics can have aneuploidy and copy number gains and losses, which hampers the detection of early, initiating events in tumorigenesis. Often, no benign precursors are known, which is why good models are essential. The mesenchymal stem cell (MSC) is the presumed cell of origin of sarcoma. In this study, MSCs of murine and canine origin are used as a model to identify driver events for sarcomas with complex genomic alterations as they transform spontaneously after long-term culture. All transformed murine but not canine MSCs formed sarcomas after subcutaneous injection in mice. Using whole genome sequencing, spontaneously transformed murine and canine MSCs displayed a complex karyotype with aneuploidy, point mutations, structural variants, inter-chromosomal translocations, and copy number gains and losses. Cross-species analysis revealed that point mutations in Tp53/Trp53 are common in transformed murine and canine MSCs. Murine MSCs with a cre-recombinase induced deletion of exon 2-10 of Trp53 transformed earlier compared to wild-type murine MSCs, confirming the contribution of loss of p53 to spontaneous transformation. Our comparative approach using transformed murine and canine MSCs points to a crucial role for p53 loss in the formation of sarcomas with complex genomics.

scholarly journals High coverage COVID-19 mRNA vaccination rapidly controls SARS-CoV-2 transmission in long-term care facilities

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Pablo M. De Salazar ◽  
Nicholas B. Link ◽  
Karuna Lamarca ◽  
Mauricio Santillana
Keyword(s):  
Long Term Care ◽  
Mitigation Strategies ◽  
Key Factors ◽  
Modeling Framework ◽  
High Coverage ◽  
Term Care ◽  
Early Effect ◽  
Care Facilities ◽  
The Relationship

Abstract Background Residents of Long-Term Care Facilities (LTCFs) represent a major share of COVID-19 deaths worldwide. Measuring the vaccine effectiveness among the most vulnerable in these settings is essential to monitor and improve mitigation strategies. Methods We evaluate the early effect of the administration of BNT162b2-mRNA vaccine to individuals older than 64 years residing in LTCFs in Catalonia, Spain. We monitor all the SARS-CoV-2 documented infections and deaths among LTCFs residents once more than 70% of them were fully vaccinated (February–March 2021). We develop a modeling framework based on the relationship between community and LTCFs transmission during the pre-vaccination period (July–December 2020). We compute the total reduction in SARS-CoV-2 documented infections and deaths among residents of LTCFs over time, as well as the reduction in the detected transmission for all the LTCFs. We compare the true observations with the counterfactual predictions. Results We estimate that once more than 70% of the LTCFs population are fully vaccinated, 74% (58–81%, 90% CI) of COVID-19 deaths and 75% (36–86%, 90% CI) of all expected documented infections among LTCFs residents are prevented. Further, detectable transmission among LTCFs residents is reduced up to 90% (76–93%, 90% CI) relative to that expected given transmission in the community. Conclusions Our findings provide evidence that high-coverage vaccination is the most effective intervention to prevent SARS-CoV-2 transmission and death among LTCFs residents. Widespread vaccination could be a feasible avenue to control the COVID-19 pandemic conditional on key factors such as vaccine escape, roll out and coverage.

scholarly journals Public acceptance of COVID-19 vaccines: cross-national evidence on levels and individual-level predictors using observational data

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e048172
Author(s):  
Marie Fly Lindholt ◽  
Frederik Jørgensen ◽  
Alexander Bor ◽  
Michael Bang Petersen
Keyword(s):  
Health Communication ◽  
Herd Immunity ◽  
Geographical Location ◽  
Vaccine Acceptance ◽  
Total N ◽  
Individual Level ◽  
Health Authorities ◽  
Personal Consequences ◽  
Western Democracies

ObjectivesThe management of the COVID-19 pandemic hinges on the approval of safe and effective vaccines but, equally importantly, on high vaccine acceptance among people. To facilitate vaccine acceptance via effective health communication, it is key to understand levels of vaccine scepticism and the demographic, psychological and political predictors. To this end, we examine the levels and predictors of acceptance of an approved COVID-19 vaccine.Design, setting and participantsWe examine the levels and predictors of acceptance of an approved COVID-19 vaccine in large online surveys from eight Western democracies that differ in terms of the severity of the pandemic and their response: Denmark, France, Germany, Hungary, Sweden, Italy, UK and USA (total N=18 231). Survey respondents were quota sampled to match the population margins on age, gender and geographical location for each country. The study was conducted from September 2020 to February 2021, allowing us to assess changes in acceptance and predictors as COVID-19 vaccine programmes were rolled out.Outcome measureThe outcome of the study is self-reported acceptance of a COVID-19 vaccine approved and recommended by health authorities.ResultsThe data reveal large variations in vaccine acceptance that ranges from 83% in Denmark to 47% in France and Hungary. Lack of vaccine acceptance is associated with lack of trust in authorities and scientists, conspiratorial thinking and a lack of concern about COVID-19.ConclusionMost national levels of vaccine acceptance fall below estimates of the required threshold for herd immunity. The results emphasise the long-term importance of building trust in preparations for health emergencies such as the current pandemic. For health communication, the results emphasise the importance of focusing on personal consequences of infections and debunking of myths to guide communication strategies.

Do researchers impact their study populations? Assessing the effect of field procedures in a long term population monitoring of sea kraits

2012 ◽  
Vol 33 (3-4) ◽  
pp. 365-372 ◽  
Author(s):  
Thomas Fauvel ◽  
François Brischoux ◽  
Marine Jeanne Briand ◽  
Xavier Bonnet
Keyword(s):  
Body Condition ◽  
New Caledonia ◽  
Stress Hormones ◽  
Population Level ◽  
Population Monitoring ◽  
Long Term Effects ◽  
Negative Effects ◽  
Short Term ◽  
Head Morphology

Long term population monitoring is essential to ecological studies; however, field procedures may disturb individuals. Assessing this topic is important in worldwide declining taxa such as reptiles. Previous studies focussed on animal welfare issues and examined short-term effects (e.g. increase of stress hormones due to handling). Long-term effects with possible consequences at the population level remain poorly investigated. In the present study, we evaluated the effects of widely used field procedures (e.g. handling, marking, forced regurgitation) both on short-term (hormonal stress response) and on long-term (changes in body condition, survival) scales in two intensively monitored populations of sea kraits (Laticauda spp.) in New Caledonia. Focusing on the most intensively monitored sites, from 2002 to 2012, we gathered approximately 11 200 captures/recaptures on 4500 individuals. Each snake was individually marked (scale clipping + branding) and subjected to various measurements (e.g. body size, head morphology, palpation). In addition, a subsample of more than 500 snakes was forced to regurgitate their prey for dietary analyses. Handling caused a significant stress hormonal response, however we found no detrimental long-term effect on body condition. Forced regurgitation did not cause any significant effect on both body condition one year later and survival. These results suggest that the strong short-term stress provoked by field procedures did not translate into negative effects on the population. Although similar analyses are required to test the validity of our conclusions in other species, our results suggest distinguishing welfare and population issues to evaluate the potential impact of population surveys.

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