scholarly journals Decomposing the sources of SARS-CoV-2 fitness variation in the United States

2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Lenora Kepler ◽  
Marco Hamins-Puertolas ◽  
David A Rasmussen

Abstract The fitness of a pathogen is a composite phenotype determined by many different factors influencing growth rates both within and between hosts. Determining what factors shape fitness at the host population-level is especially challenging because both intrinsic factors like pathogen genetics and extrinsic factors such as host behavior influence between-host transmission potential. This challenge has been highlighted by controversy surrounding the population-level fitness effects of mutations in the SARS-CoV-2 genome and their relative importance when compared against non-genetic factors shaping transmission dynamics. Building upon phylodynamic birth–death models, we develop a new framework to learn how hundreds of genetic and non-genetic factors have shaped the fitness of SARS-CoV-2. We estimate the fitness effects of all amino acid variants and several structural variants that have circulated in the United States between February 2020 and March 2021 from viral phylogenies. We also estimate how much fitness variation among pathogen lineages is attributable to genetic versus non-genetic factors such as spatial heterogeneity in transmission rates. Before September 2020, most fitness variation between lineages can be explained by background spatial heterogeneity in transmission rates across geographic regions. Starting in late 2020, genetic variation in fitness increased dramatically with the emergence of several new lineages including B.1.1.7, B.1.427, B.1.429 and B.1.526. Our analysis also indicates that genetic variants in less well-explored genomic regions outside of Spike may be contributing significantly to overall fitness variation in the viral population.

2020 ◽  
Author(s):  
Lenora Kepler ◽  
Marco Hamins-Puertolas ◽  
David A. Rasmussen

AbstractThe fitness of a pathogen is composite phenotype determined by many different factors influencing growth rates both within and between hosts. Determining what factors shape fitness at the host population-level is especially challenging because both intrinsic factors like pathogen genetics and extrinsic factors such as host behaviour influence between-host transmission potential. These challenges have been highlighted by controversy surrounding the population-level fitness effects of mutations in the SARS-CoV-2 genome and their relative importance when compared against non-genetic factors shaping transmission dynamics. Building upon phylodynamic birth-death models, we develop a new framework to learn how hundreds of genetic and non-genetic factors have shaped the fitness of SARS-CoV-2. We estimate the fitness effects of all amino acid variants and several structural variants that have circulated in the United States between February and September 2020 from viral phylogenies. We also estimate how much fitness variation among pathogen lineages is attributable to genetic versus non-genetic factors such as spatial heterogeneity in transmission rates. Up to September 2020, most fitness variation between lineages can be explained by background spatial heterogeneity in transmission rates across geographic regions. Furthermore, no genetic variant including the Spike D614G mutation has had a significant effect on population-level fitness. Instead, the rapid increase in the frequency of the Spike D614G can be explained by the variant having a spatial transmission advantage due to first establishing in regions with higher transmission rates during the earliest stages of the pandemic.


Author(s):  
Wendy Thompson ◽  
Leanne Teoh ◽  
Colin C. Hubbard ◽  
Fawziah Marra ◽  
David M. Patrick ◽  
...  

Abstract Objective: Our objective was to compare patterns of dental antibiotic prescribing in Australia, England, and North America (United States and British Columbia, Canada). Design: Population-level analysis of antibiotic prescription. Setting: Outpatient prescribing by dentists in 2017. Participants: Patients receiving an antibiotic dispensed by an outpatient pharmacy. Methods: Prescription-based rates adjusted by population were compared overall and by antibiotic class. Contingency tables assessed differences in the proportion of antibiotic class by country. Results: In 2017, dentists in the United States had the highest antibiotic prescribing rate per 1,000 population and Australia had the lowest rate. The penicillin class, particularly amoxicillin, was the most frequently prescribed for all countries. The second most common agents prescribed were clindamycin in the United States and British Columbia (Canada) and metronidazole in Australia and England. Broad-spectrum agents, amoxicillin-clavulanic acid, and azithromycin were the highest in Australia and the United States, respectively. Conclusion: Extreme differences exist in antibiotics prescribed by dentists in Australia, England, the United States, and British Columbia. The United States had twice the antibiotic prescription rate of Australia and the most frequently prescribed antibiotic in the US was clindamycin. Significant opportunities exist for the global dental community to update their prescribing behavior relating to second-line agents for penicillin allergic patients and to contribute to international efforts addressing antibiotic resistance. Patient safety improvements will result from optimizing dental antibiotic prescribing, especially for antibiotics associated with resistance (broad-spectrum agents) or C. difficile (clindamycin). Dental antibiotic stewardship programs are urgently needed worldwide.


2021 ◽  
pp. 106864
Author(s):  
Kristen Nishimi ◽  
Emma Glickman ◽  
Kathryn Smith ◽  
Eran Ben-Joseph ◽  
Shelley Carson ◽  
...  

2018 ◽  
Vol 5 (6) ◽  
Author(s):  
Jonathan Colasanti ◽  
Jeri Sumitani ◽  
C Christina Mehta ◽  
Yiran Zhang ◽  
Minh Ly Nguyen ◽  
...  

Abstract Background Rapid entry programs (REPs) improve time to antiretroviral therapy (ART) initiation (TAI) and time to viral suppression (TVS). We assessed the feasibility and effectiveness of a REP in a large HIV clinic in Atlanta, Georgia, serving a predominately un- or underinsured population. Methods The Rapid Entry and ART in Clinic for HIV (REACH) program was implemented on May 16, 2016. We performed a retrospective cohort study with the main independent variable being period of enrollment: January 1, 2016, through May 15, 2016 (pre-REACH); May 16, 2016, through July 31, 2016 (post-REACH). Included individuals were HIV-infected and new to the clinic with detectable HIV-1 RNA. Six-month follow-up data were collected for each participant. Survival analyses were conducted for TVS. Logistic and linear regression analyses were used to evaluate secondary outcomes: attendance at first clinic visit, viral suppression, TAI, and time to first attended provider visit. Results There were 117 pre-REACH and 90 post-REACH individuals. Median age (interquartile range [IQR]) was 35 (25–45) years, 80% were male, 91% black, 60% men who have sex with men, 57% uninsured, and 44% active substance users. TVS decreased from 77 (62–96) to 57 (41–70) days (P < .0022). Time to first attended provider visit decreased from 17 to 5 days, and TAI from 21 to 7 days (P < .0001), each remaining significant in adjusted models. Conclusions This is the largest rapid entry cohort described in the United States and suggests that rapid entry is feasible and could have a positive impact on HIV transmission at the population level.


2021 ◽  
pp. 088506662110537
Author(s):  
Po-Yang Tsou ◽  
Chia-Hung Yo ◽  
Yenh-Chen Hsein ◽  
Gregory Yungtum ◽  
Wan-Ting Hsu ◽  
...  

Background Epidemiologic studies are needed for monitoring population-level trends in sepsis. This study examines sepsis-causing microorganisms from 2006 to 2014 in the United States using data from the Nationwide Inpatient Sample database. Methods 7 860 686 adults hospitalized with sepsis were identified using a validated ICD-9 coding approach. Associated microorganisms were identified by ICD-9 code and classified by major groups (Gram-positive, Gram-negative, fungi, anaerobes) and specific species for analysis of their incidence and mortality. Results The rate of sepsis incidence has increased for all four major categories of pathogens, while the mortality rate decreased. In 2014, Gram-negative pathogens had a higher incidence than Gram-positives. Anaerobes increased the fastest with an average annual increase of 20.17% (p < 0.001). Fungi had the highest mortality (19.28%) and the slowest annual decrease of mortality (−2.31%, p = 0.006) in 2013, while anaerobic sepsis had the highest hazard of mortality (adjusted HR 1.60, 95% CI 1.53-1.66). Conclusions Gram-negative pathogens have replaced Gram-positives as the leading cause of sepsis in the United States in 2014 during the study period (2006-2014). The incidence of anaerobic sepsis has an annual increase of 20%, while the mortality of fungal sepsis has not decreased at the same rate as other microorganisms. These findings should inform the diagnosis and management of septic patients, as well as the implementation of public health programs.


2019 ◽  
Vol 7 (5) ◽  
pp. 900-913 ◽  
Author(s):  
Miriam K. Forbes ◽  
Robert F. Krueger

The full scope of the impact of the Great Recession on individuals’ mental health has not been quantified to date. In this study we aimed to determine whether financial, job-related, and housing impacts experienced by individuals during the recession predicted changes in the occurrence of symptoms of depression, generalized anxiety, panic attacks, and problematic alcohol use or other substance use. Longitudinal survey data ( n = 2,530 to n = 3,293) from the national Midlife in the United States study that were collected before (2003–2004) and after (2012–2013) the Great Recession were analyzed. The population-level trend was toward improvements in mental health over time. However, for individuals, each recession impact experienced was associated with long-lasting and transdiagnostic declines in mental health. These relationships were stronger for some sociodemographic groups, which suggests the need for additional support for people who suffer marked losses during recessions and for those without a strong safety net.


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