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1.
Innovation in Aging ; 5:231-231, 2021.
Article in English | Web of Science | ID: covidwho-2011663
2.
Topics in Antiviral Medicine ; 30(1 SUPPL):17, 2022.
Article in English | EMBASE | ID: covidwho-1881061

ABSTRACT

Background: Knowing the true incidence of HIV-1 infections (recent infections) among people newly diagnosed is pivotal to monitoring the course of the epidemic. We have developed a Primer ID Next Gen Sequencing (PID-NGS) assay to identify recent infection by measuring within-host viral diversity over multiple regions of the HIV-1 genome. We implemented a state-wide project to identify recent infections and transmitted drug resistance mutations (DRMs) in diagnostic samples in near real time. Methods: Serum samples from individuals with newly HIV-1 diagnoses (diagnostic sample collected within 30 days of diagnosis) were sequenced. PID-NGS libraries were constructed covering the coding regions for protease, a portion of reverse transcriptase, integrase, and the env gene. The use of the PID-NGS strategy allows for significant error correction and also a definition of the sampling depth of the viral population. Recent infection was defined as within 9-month of infection. DRMs were summarized at detection sensitivities of 30%, 10% and 1% based on viral population sampling depth. Results: From Jan 2018 to Jun 2021, we successfully sequenced partial genomes from 743 individuals with new diagnoses. Year 2020 had the lowest number of new diagnoses (Fig 1a, red bar). Overall, 39.2% of samples were inferred to have represented infection within the previous 9 months. Percent of recent infection varied significantly over the years, increasing from 29.6% in late 2018 to 50.9% in early 2020, but decreasing significantly to 32.7% in 2021 (Fig 1a, blue lines). Individuals younger than 30 y/o were more likely to be identified with recent infection (p<0.01). NNRTI DRMs, especially K103N, were the most abundant DRMs. Fig 1b shows the trend of DRMs over the four years. We observed a trend of decrease in the overall NNRTI DRMs and an increase in the NRTI DRMs in the population. Further analysis suggests that the increase in NRTI DRMs were from TAMs and their revertants, while clinically important NRTI DRMs (K65R and M184) were low (<1%). Conclusion: We have demonstrated a state-wide, all-in-one platform to monitor HIV-1 recency and DRMs in new diagnoses. The number of new diagnoses decreased significantly in 2020 in concert with the COVID-19 pandemic which suggests a decrease in overall HIV testing. The decline in the percentage of recent infections in early 2021 signals a return to broader HIV-1 testing and diagnosis. The increase of other NRTI DRMs suggests ongoing evolution at these sites within the viral population.

3.
Topics in Antiviral Medicine ; 30(1 SUPPL):38-39, 2022.
Article in English | EMBASE | ID: covidwho-1880187

ABSTRACT

Background: Cardiopulmonary symptoms and reduced exercise capacity can persist after SARS-CoV-2 infection. Mechanisms of post-acute sequelae of COVID-19 ("PASC" or "Long COVID") remain poorly understood. We hypothesized that systemic inflammation would be associated with reduced exercise capacity and pericardial/myocardial inflammation. Methods: As part of a COVID recovery cohort (NCT04362150) we assessed symptoms, biomarkers, and echocardiograms in adults >2 months after PCR-confirmed SARS-CoV-2 infection. In a subset, we performed cardiac magnetic resonance imaging (CMR), ambulatory rhythm monitoring (RM), and cardiopulmonary exercise testing (CPET) >12 months after acute infection. Associations between symptoms and oxygen consumption (VO2), cardiopulmonary parameters and biomarkers were evaluated using linear and logistic regression with adjustment for age, sex, BMI, and time since infection. Results: We studied 120 participants (median age 51, 42% female, and 47% had cardiopulmonary symptoms at median 7 months after acute infection). Elevated hsCRP was associated with symptoms (OR 1.32 per doubling, 95%CI 1.01-1.73, p=0.04). No differences in echocardiographic indices were found except for presence of pericardial effusions among those with symptoms (p=0.04). Of the subset (n=33) who underwent CMR at a median 17 months, all had normal cardiac function (LVEF 53-76%), 9 (27%) had pericardial effusions and none had findings suggestive of prior myocarditis. There were no differences on RM by symptoms. On CPET, 33% had reduced exercise capacity (peak VO2 <85% predicted). Individuals with symptoms had lower peak VO2 compared to those reporting recovery (28.4 vs 21.4 ml/kg/min, p=0.04, Figure). Elevated hsCRP was independently associated with lower peak VO2 after adjustment (-9.8 ml/kg/min per doubling, 95%CI-17.0 to-2.5;p=0.01, Figure). The predominant mechanism of reduced peak VO2 was chronotropic incompetence (HR 19% lower than predicted, 95%CI 11-26%;p<0.0001, Figure). Chronotropic incompetence on CPET correlated with lower peak HR during ambulatory RM (p<0.001). Conclusion: Persistent systemic inflammation (hsCRP) is associated with pericardial effusions and reduced exercise capacity > 1 year after acute SARS-CoV-2 infection. This finding appears to be driven mainly by chronotropic incompetence rather than respiratory compromise, cardiac pump dysfunction, or deconditioning. Evaluation of therapeutic strategies to target inflammation and/or chronotropy to alleviate PASC is urgently needed.

5.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-338328

ABSTRACT

BACKGROUND: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 "PASC" or "Long COVID") remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring. METHODS: We performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection in the UCSF Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC;NCT04362150 ) and correlated findings with previously measured biomarkers. We used logistic regression to estimate associations with PASC symptoms (dyspnea, chest pain, palpitations, and fatigue) adjusted for confounders and linear regression to estimate differences between those with and without symptoms adjusted for confounders. RESULTS: Out of 120 participants in the cohort, 46 participants (unselected for symptom status) had at least one advanced cardiac test performed at median 17 months following initial SARS-CoV-2 infection. Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), higher extracellular volume was associated with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/23 (57%) with cardiopulmonary symptoms or fatigue had reduced exercise capacity (peak VO 2 <85% predicted) compared to 2/16 (13%) without symptoms (p=0.008). The adjusted difference in peak VO 2 was 5.9 ml/kg/min lower (-9.6 to -2.3;p=0.002) or -21% predicted (-35 to -7;p=0.006) among those with symptoms. Chronotropic incompetence was the primary abnormality among 9/15 (60%) with reduced peak VO 2 . Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187;p=0.03). Inflammatory markers (hsCRP, IL-6, TNF-alpha) and SARS-CoV-2 antibody levels measured early in PASC were negatively correlated with peak VO 2 more than 1 year later. CONCLUSIONS: Cardiopulmonary symptoms and elevated inflammatory markers present early in PASC are associated with objectively reduced exercise capacity measured on cardiopulmonary exercise testing more than 1 year following COVID-19. Chronotropic incompetence may explain reduced exercise capacity among some individuals with PASC. Clinical Perspective: What is New?Elevated inflammatory markers in early post-acute COVID-19 are associated with reduced exercise capacity more than 1 year later.Impaired chronotropic response to exercise is associated with reduced exercise capacity and cardiopulmonary symptoms more than 1 year after SARS-CoV-2 infection.Findings on ambulatory rhythm monitoring point to perturbed autonomic function, while cardiac MRI findings argue against myocardial dysfunction and myocarditis. Clinical Implications: Cardiopulmonary testing to identify etiologies of persistent symptoms in post-acute sequalae of COVID-19 or "Long COVID" should be performed in a manner that allows for assessment of heart rate response to exercise. Therapeutic trials of anti-inflammatory and exercise strategies in PASC are urgently needed and should include assessment of symptoms and objective testing with cardiopulmonary exercise testing.

6.
Respirology ; 27(SUPPL 1):124, 2022.
Article in English | EMBASE | ID: covidwho-1816636

ABSTRACT

Introduction/Aim: The COVID-19 pandemic has led to implementation of telehealth pulmonary rehabilitation (PR), which remains a favourable alternative to the traditional centre-based model in jurisdictions where the risk of patient vulnerability to COVID-19 is high. This study compares the outcomes between telehealth PR and centre-based PR in people with chronic respiratory disease. Methods: Retrospective data were collected between December 2020 and October 2021 from chronic respiratory disease patients who undertook 6-8 weeks of either twice weekly supervised centre-based PR or telehealth PR involving once-weekly telephone/video calls from an experienced clinician guiding patients on home-based exercise. Telehealth PR was the default model of care, with centrebased PR only offered if telehealth was not possible due to safety, feasibility or previous failure of telehealth PR or if patients (ILD only) agreed to participate in a specific research project that involved centre-based attendance. Outcomes included functional capacity, dyspnoea, health related quality of life (HRQoL) and global rating of change. Results: Thirty-two patients undertook centre-based PR (age 70(8) years, ILD = 20(63%), COPD = 9(28%), other = 3 (9%)) and 32 patients undertook telehealth PR (age 72(12), COPD = 20(63%), ILD = 7(22%), other = 5(15%)). There were no significant differences between groups for functional capacity, dyspnoea or HRQoL (Table 1). However, a greater proportion of patients perceived their overall condition had improved following telehealth PR (63% vs. 47%, p = 0.009). Both groups achieved significant improvements in HRQoL at end rehabilitation. Significant improvement in functional capacity following PR was seen only in the centre-based group (n = 29), although this outcome was only available in 12 (38%) telehealth PR patients. Conclusion: Telehealth PR produces improvements in functional capacity and HRQoL that are equivalent to centre based PR and is associated with a perceived overall benefit by a greater proportion of participants. Telehealth PR is a suitable alternative to the standard centre-based approach telerehabilitation may not be equivalent to centre-base. (Figure Presented).

7.
AIAA Aviation and Aeronautics Forum and Exposition, AIAA AVIATION Forum 2021 ; 2021.
Article in English | Scopus | ID: covidwho-1770968

ABSTRACT

This paper presents details of a market segmentation analysis conducted using data from a stated preference survey we designed to model competition among an electric air taxi service, autonomous ground vehicles, and traditional ground vehicles for an air taxi shuttle to major commercial airports in the United States. This paper is based on data collected from January 8 to April 7, 2021, and includes 2,439 responses from individuals who took at least two trips by air in 2019 before COVID-19;have annual household incomes of at least $75K;and live in the Atlanta, Boston, Chicago, Dallas–Ft. Worth, Los Angeles, New York, or San Francisco combined statistical areas (CSAs). Factor analysis of respondents’ perceptions of electric vertical take-off and landing (eVTOL) aircraft identified two dimensions: Concern and Enthusiasm. Cluster analysis of the scores on these factors identified seven meaningful clusters, which differed on a variety of demographic, travel behavior, and attitudinal variables, as well as on respondents’ inclination to adopt eVTOL for traveling to a commercial airport. © 2021, American Institute of Aeronautics and Astronautics Inc, AIAA. All rights reserved.

9.
Revue du Praticien ; 71(8):819-826, 2021.
Article in French | MEDLINE | ID: covidwho-1678889
10.
Capjournal ; - (30):28-32, 2021.
Article in English | Web of Science | ID: covidwho-1567468

ABSTRACT

Astronomers for Planet Earth (A4E) is a global collective, whose main goal is to communicate the fragility of our planet from an astronomical perspective. A4E works hard to equally engage with astronomers and educators worldwide, by encouraging the communities to reduce emissions and providing a space to collaborate and share resources. These actions have led to increased sustainability and the incorporation of climate change lessons and activities into teaching and outreach. With the global shift to online communication due to Covid-19, Astronomers for Planet Earth has utilised digital tools in the form of online conferences and seminars, high-impact journal articles, webinars, social media, and video production to engage its audience and grow a membership of around 1300 astronomers in 70 countries around the world. Our article addresses the importance of communicating the climate crisis from an astronomical perspective and explores the successes and challenges of our group's virtual communication with the astronomy community and the general public thus far.

11.
International Journal of Developmental Disabilities ; : 1-9, 2021.
Article in English | Taylor & Francis | ID: covidwho-1429122
12.
IEEE High Performance Extreme Computing Conference (HPEC) ; 2020.
Article in English | Web of Science | ID: covidwho-1395949

ABSTRACT

Pandemic measures such as social distancing and contact tracing can be enhanced by rapidly integrating dynamic location data and demographic data. Projecting billions of longitude and latitude locations onto hundreds of thousands of highly irregular demographic census block polygons is computationally challenging in both research and deployment contexts. This paper describes two approaches labeled "simple" and "fast". The simple approach can be implemented in any scripting language (Matlab/Octave, Python, Julia, R) and is easily integrated and customized to a variety of research goals. This simple approach uses a novel combination of hierarchy, sparse bounding boxes, polygon crossing-number, vectorization, and parallel processing to achieve 100,000,000+ projections per second on 100 servers. The simple approach is compact, does not increase data storage requirements, and is applicable to any country or region. The fast approach exploits the thread, vector, and memory optimizations that are possible using a low-level language (C++) and achieves similar performance on a single server. This paper details these approaches with the goal of enabling the broader community to quickly integrate location and demographic data.

13.
Critical Care Medicine ; 49(1):150-150, 2021.
Article in English | Web of Science | ID: covidwho-1326646
14.
Revue du Praticien ; 71(4):359, 2021.
Article in French | MEDLINE | ID: covidwho-1282971
15.
Revue du Praticien ; 71(3):239-244, 2021.
Article in French | MEDLINE | ID: covidwho-1279130
16.
Topics in Antiviral Medicine ; 29(1):135-136, 2021.
Article in English | EMBASE | ID: covidwho-1250916

ABSTRACT

Background: We previously showed that β-D-N4-hydroxycytidine (rNHC) and its orally bioavailable prodrug, molnupiravir, acts as a broad-spectrum antiviral against coronaviruses in vitro and in vivo through lethal mutagenesis. Molnupiravir is currently in clinical trials for the treatment of SARS-CoV-2 infection. However, there are concerns that rNHC could be metabolized to dNHC and cause mutations in host cells. We examined the in vitro antiviral and mammalian cell mutagenic activity of three different nucleoside/base analogs, rNHC, favipiravir, and ribavirin, on SARS-CoV-2. We further examined the in vitro genotoxicity of a panel of antiviral nucleotide/nucleoside analogs, including rNHC, using a modified HPRT gene mutation assay. Methods: A549-hACE2 cells were infected with SARS-CoV-2 in the presence of nucleoside analogs. After 48 hours, the supernatants were collected and viral RNA was extracted. We constructed multiplexed-Primer ID libraries from viral RNA and sequenced them using MiSeq. HPRT knockout assays were performed using CHO-K1 cells treated with a panel of nucleotide/nucleoside analogs for 32 days. After 6-thioguanine selection, resistant cell colonies were counted as a measure of HPRT knockout mutations in host cells, and HPRT mRNA was sequenced from selected colonies. Results: rNHC showed dose-dependent antiviral and mutagenic effects against SAR-CoV-2 in vitro. In the 10 μM group, we found 7-fold and 14-fold increases in the overall substitution rate and the C to U mutation rate, respectively. The HPRT assay showed an rNHC dose-dependent increase in the number of resistant colonies with HPRT gene mutations. Other analogs showed no significant increase in the number of 6-thioG resistant colonies except for a slight increase with favipiravir (Fig 1a). Most colonies had missense substitutions or frame-shift deletions within HPRT mRNA, with most being distinct. Conclusion: rNHC showed a dose-dependent inhibition and mutagenic effect of SAR-CoV-2 in vitro. However, rNHC would be expected to be metabolized into the deoxynucleotide pool (by host RNR), resulting in DNA mutation of dividing mammalian cells. We demonstrated such mutagenic potential in a simple mammalian cell detection scheme. Molnupiravir has considerable potential as an orally bioavailable direct acting antiviral against SARS-CoV2 early in infection, especially in high risk patients. However, clinical use should be carefully considered in light of its potential mutagenic effects on the host.

18.
Critical Care Medicine ; 49(1 SUPPL 1):150, 2021.
Article in English | EMBASE | ID: covidwho-1194011

ABSTRACT

INTRODUCTION: Caring for critically ill children with known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires significant changes to usual pediatric intensive care unit operations related to infection control policies and frequent evolution of clinical care practice. We hypothesized that patients with known or suspected SARS-CoV-2 would more often experience delays in timely antibiotic administration. METHODS: We performed a retrospective cohort study including all children with suspected sepsis admitted to our tertiary PICU from March 16 through June 18, 2020. Suspected sepsis was defined by an order for a broadspectrum antibiotic and blood culture. Children with known or suspected SARS-CoV-2 were defined by admission to the Pediatric Special Treatment Unit (PSTU), an isolation unit within the PICU dedicated to care of SARS-CoV-2 patients. The primary outcome of median time to antibiotic administration was compared using the Mann-Whitney-U test. Secondary outcomes included the proportion of antibiotics administered within 1 hour of the order and sepsis pathway utilization. Fisher's exact test was used for comparison of secondary outcomes. RESULTS: A total of 155 sepsis episodes were evaluated, including 14 with known/suspected SARS-CoV-2 and 141 with non-SARS-CoV-2 sepsis. Median time to antibiotic administration was 70.5 minutes in known/suspected SARSCoV- 2 versus 103 minutes in non-SARS-CoV-2 sepsis (NS). Secondary outcomes were also not different between groups. Known/suspected SARS-CoV-2 patients received 36% of new antibiotics within 60 minutes as compared to 46% of non-SARS-CoV-2 patients. Pathway utilization was 29% in known/suspected SARS-CoV-2 and 23% in non-SARSCoV- 2 patients. CONCLUSIONS: Despite significant operational changes enacted to care for SARS-CoV-2 patients, time to antibiotic administration and utilization of the sepsis pathway were no different than in non-SARS-CoV-2 patients with suspected sepsis. Operational challenges may have been overcome by a staffing model that emphasized attending physicians as well as a higher nurse to patient ratio for this population.

19.
Revue du Praticien ; 70(10):1066, 2020.
Article in French | MEDLINE | ID: covidwho-1141050
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