High-Resolution Agent-Based Modeling of COVID-19 Spreading in a Small Town

Amid the ongoing COVID-19 pandemic, public health authorities and the general population are striving to achieve a balance between safety and normalcy. Ever changing conditions call for the development of theory and simulation tools to finely describe multiple strata of society while supporting the evaluation of “what-if” scenarios. Particularly important is to assess the effectiveness of potential testing approaches and vaccination strategies. Here, an agent-based modeling platform is proposed to simulate the spreading of COVID-19 in small towns and cities, with a single-individual resolution. The platform is validated on real data from New Rochelle, NY—one of the first outbreaks registered in the United States. Supported by expert knowledge and informed by reported data, the model incorporates detailed elements of the spreading within a statistically realistic population. Along with pertinent functionality such as testing, treatment, and vaccination options, the model accounts for the burden of other illnesses with symptoms similar to COVID-19. Unique to the model is the possibility to explore different testing approaches—in hospitals or drive-through facilities—and vaccination strategies that could prioritize vulnerable groups. Decision-making by public authorities could benefit from the model, for its fine-grain resolution, open-source nature, and wide range of features

Next-generation sequencing for diagnosis of thoracic aortic aneurysms and dissections: diagnostic yield, novel mutations and genotype phenotype correlations

Additional file 1. Complementary data on primer sequences, SKI amplification and survival analyses

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVE: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Exploring a COVID-19 Endemic Scenario: High-Resolution Agent-Based Modeling of Multiple Variants

Our efforts as a society to combat the ongoing COVID-19 pandemic are continuously challenged by the emergence of new variants. These variants can be more infectious than existing strains and many of them are also more resistant to available vaccines. The appearance of these new variants cause new surges of infections, exacerbated by infrastructural difficulties, such as shortages of medical personnel or test kits. In this work, a high-resolution computational framework for modeling the simultaneous spread of two COVID-19 variants: a widely spread base variant and a new one, is established. The computational framework consists of a detailed database of a representative U.S. town and a high-resolution agent-based model that uses the Omicron variant as the base variant and offers flexibility in the incorporation of new variants. The results suggest that the spread of new variants can be contained with highly efficacious tests and mild loss of vaccine protection. However, the aggressiveness of the ongoing Omicron variant and the current waning vaccine immunity point to an endemic phase of COVID-19, in which multiple variants will coexist and residents continue to suffer from infections

Predicting the Effects of Waning Vaccine Immunity Against COVID-19 through High-Resolution Agent-Based Modeling

The potential waning of the vaccination immunity to COVID-19 could pose threats to public health, as it is tenable that the timing of such waning would synchronize with the near-complete restoration of normalcy. Should also testing be relaxed, a resurgent COVID-19 wave in winter 2021/2022 might be witnessed. In response to this risk, an additional vaccine dose, the booster shot, is being administered worldwide. A projected study with an outlook of 6 months explores the interplay between the rate at which boosters are distributed and the extent to which testing practices are implemented, using a highly granular agent-based model tuned on a medium-sized US town. Theoretical projections indicate that the administration of boosters at the rate at which the vaccine is currently administered could yield a severe resurgence of the pandemic. Projections suggest that the peak levels of mid-spring 2021 in the vaccination rate may prevent such a scenario to occur, although exact agreement between observations and projections should not be expected due to the continuously evolving nature of the pandemic. This study highlights the importance of testing, especially to detect asymptomatic individuals in the near future, as the release of the booster reaches full speed