Hiv Detection in Wastewater as a New Epidemiological Tool

Background: Wastewater represents a broad, immediate, and unbiased accounting of the pathgens in the population. We aimed to develop methods to track HIV in wastewater utilizing a viral detection pipeline adapted from platforms developed to track SARS-COV-2. Method(s): We used samples from 6 wastewater treatment plants in the Houston area. We focused on regions of higher prevalence and lower prevalence. First, employing wastewater processing and nucleic acid extraction methods described by our group to detect SARS-COV-2, we tested a single high and low prevalence site in triplicate with all 3 primer sets. nucleic acid extracts from HIV and SIV cell culture supernatants were used as controls. Next, in subsequent samples, RT-PCR reactions with detections were subjected to gel electrophoresis to determine the amplified product sizes. To further confirm HIV detection, we sequenced the RT-PCR products and compared the proportion of reads which mapped to the expected amplified product. In a later set of studies, we fractionated samples into supernatant and pellet. We further tested HIV presence by performing whole virome sequencing on the extracts from some samples that produced detections and mapped reads to published genomes. A crAssphage genome was used as a negative control. Result(s): Samples from all sites resulted in signal detection at least once. Only reactions with gag and pol primers appeared to amplify the expected product. Products from the HIV positive control mapped almost exclusively to the HIV genome (97-100% of reads), with a fraction of reads from the SIV negative control doing the same (16-18% of reads). The ltr and pol products did not map the HIV genome while gag products did (34-44% of reads). Among the fractionated sample, in total, 6 supernatant fractions produced no detection compared to 7 of 8 pellet fractions. The whole virome sequencing produced reads that mapped to the HIV genome with at least 8X depth coverage. The sample with the lowest Ct detection (26) yielded HIV coverage several logs greater than those samples with higher Ct detection (37). Reads from all samples mapped to at least 20% of the HIV genome. Conclusion(s): This work provides the first evidence that HIV can be detected in municipal wastewater systems and has the potential to be developed into a new public health tool.

Modeling SARS-CoV-2 RNA degradation in small and large sewersheds

Wastewater-based epidemiology has played a significant role in monitoring the COVID-19 pandemic, yet little is known about degradation of SARS-CoV-2 in sewer networks. Here, we used advanced sewershed modeling software to simulate SARS-CoV-2 RNA degradation in sewersheds across Houston, TX under various temperatures and decay rates. Moreover, a novel metric, population times travel time (PT), was proposed to identify localities with a greater likelihood of undetected COVID-19 outbreaks and to aid in the placement of upstream samplers. Findings suggest that travel time has a greater influence on RNA degradation across the sewershed as compared to temperature. SARS-CoV-2 RNA degradation at median travel times was approximately two times greater in 20 degrees C wastewater between the small sewershed, Chocolate Bayou, and the larger sewershed, 69th Street. Lastly, placement of upstream samplers according to the PT metric can provide a more representative snapshot of disease incidence in large sewersheds. This study helps to elucidate discrepancies between SARS-CoV-2 viral load in wastewater and clinical incidence of COVID-19. Incorporating travel time and SARS-CoV-2 RNA decay can improve wastewater surveillance efforts.

Low Incidence of COVID-19 Infection in Patients with Acute Myeloid Leukemia Undergoing Reduced Intensity/Venetoclax Based Treatment: Initial Results of the PACE Prospective Clinical Study from the UK Trials Acceleration Program

The impact of Coronavirus disease 2019 (COVID-19) on outcomes in patients with cancer remains unclear. Acute Myeloid Leukemia (AML)/high-risk myelodysplasia (MDS) are common hematological malignancies resulting in profound immunosuppression, which is exacerbated by intensive and less-intensive chemotherapy. Importantly, venetoclax based regimens have been increasingly used during the pandemic as a strategy to reduce patient hospitalization however, there is little information concerning the impact of such regimens on COVID-19 infection rates. We therefore opened a prospective clinical study (PACE), at the start of the current pandemic in April 2020 to characterize the risk of COVID-19 infection in patients with AML/MDS-EB2 receiving intensive or non-intensive treatment, including patients treated with venetoclax-based regimens. The primary aim was to determine the incidence of COVID-19 in patients with AML /MDS-EB2 including both, prior to study entry and during treatment until 4 weeks after the last cycle of treatment. Secondary aims were to: characterize the presentation of COVID-19;define the severity and type of both non-COVID-19 and COVID-19 infections;and undertake an exploratory analysis to quantify the incidence of COVID-19 infection in patients receiving (less-intensive) venetoclax based regimens. All analysis conducted to date has been descriptive. 211/230 recruited patients had full treatment histories available, of whom 116 patients received intensive chemotherapy and 95 low intensity regimens. 48 patients received a venetoclax-based regimen. The median age of the non-intensive treatment arm was 72 years;(range 19.1-86.5) and of the intensive arm was 59 years (range 16.1-76.1). There were more cases of secondary AML and relapsed disease in the non-intensive arm as compared to the intensive arm. 25/226 evaluable patients tested positive for COVID-19 as defined by positive SARS-CoV2 PCR test, 10 with a prior diagnosis at study entry and 15 tested positive during the study. The incidence of COVID-19 infection for patients with AML/MDS-EB2 was 11.1% (90%CI: 7.8%-15.1%) (Table). A lower proportion of patients (n=6/91 6.6%) undergoing non-intensive treatment suffered COVID-19 as compared to those undergoing more intensive chemotherapy regimens (n=19/116, 16.4%). Specifically, only 3/48 (6.3%) patients undergoing a venetoclax regimen were infected with SARS-CoV2. The most common presenting symptoms of COVID-19 in this study, regardless of the intensity of chemotherapy, was fever and cough with 6/25 patients asymptomatic. The risk of death at 30 days following study entry in patients who had prior COVID-19 infection or who contracted COVID-19 during this period was 13.6%, compared to 3.9% in the overall cohort without COVID-19 infection. There was a lower incidence of non-COVID-19 related infections in patients receiving venetoclax-based regimens, n=43 infections in 24 (50.0%) of patients;with 313 infections in 94 (81%) of intensively treated patients. The overall occurrence of non-COVID-19 infection in the non-intensive arm was 87 infections in 50 (54.9%) patients. Our multi-center study provides real-world estimates for the incidence and presentation of COVID-19 infection in a cohort of patients with AML/MDS-EB2, and indicates a higher risk of death at 30 days in patients with prior COVID-19 infection prior to, or during treatment. Venetoclax based, and other non-intensive, regimens, increasingly implemented during the pandemic, to minimize patient exposure and reduce usage of hospital beds, appeared to be associated with a low incidence of COVID-19. Further follow-up will be required to understand the long-term impact of this strategy. Analysis of immune responses to COVID-19 infection and vaccination is on-going. Acknowledgments: This study was funded by Cure Leukaemia under the Trials Acceleration Program (TAP), and grants from BMS and Blood Cancer UK. [Formula presented] Disclosures: Loke: Novartis: Other: Travel;Janssen: Honoraria;Amgen: Honoraria;Pfizer: Honoraria;Daichi Sankyo: Other: Travel. K apper: Pfizer: Consultancy, Speakers Bureau;Astellas: Ended employment in the past 24 months, Speakers Bureau;Jazz: Consultancy, Speakers Bureau;Novartis: Consultancy, Research Funding, Speakers Bureau. Khan: Abbvie: Honoraria;Astellas: Honoraria;Takeda: Honoraria;Jazz: Honoraria;Gilead: Honoraria;Novartis: Honoraria. Dillon: Amgen: Other: Research support (paid to institution);Astellas: Consultancy, Other: Educational Events, Speakers Bureau;Menarini: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Session chair (paid to institution), Speakers Bureau;Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: educational events;Jazz: Other: Education events;Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research Support, Educational Events;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees. Culligan: AbbVie Ltd: Honoraria, Speakers Bureau;Celgene Ltd: Honoraria, Speakers Bureau;Gilead: Honoraria, Speakers Bureau;Jazz Pharma: Honoraria, Speakers Bureau;Takeda UK Ltd: Honoraria, Speakers Bureau. McMullin: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Other: clinical trial support, Research Funding;Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AOP Orphan: Research Funding, Speakers Bureau. Murthy: Abbvie: Other: support to attend educational conferences. Craddock: Novartis Pharmaceuticals: Other: Advisory Board;Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Enhanced stress-resilience training for surgical trainees.

INTRODUCTION: Core surgical training programmes are associated with a high risk of burnout. This study aimed to assess the influence of a novel enhanced stress-resilience training (ESRT) course delivered at the start of core surgical training in a single UK statutory education body. METHOD: All newly appointed core surgical trainees (CSTs) were invited to participate in a 5-week ESRT course teaching mindfulness-based exercises to develop tools to deal with stress at work and burnout. The primary aim was to assess the feasibility of this course; secondary outcomes were to assess degree of burnout measured using Maslach Burnout Inventory (MBI) scoring. RESULTS: Of 43 boot camp attendees, 38 trainees completed questionnaires, with 24 choosing to participate in ESRT (63.2 per cent; male 13, female 11, median age 28 years). Qualitative data reflected challenges delivering ESRT because of arduous and inflexible clinical on-call rotas, time pressures related to academic curriculum demands and the concurrent COVID-19 pandemic (10 of 24 drop-out). Despite these challenges, 22 (91.7 per cent) considered the course valuable and there was unanimous support for programme development. Of the 14 trainees who completed the ESRT course, nine (64.3 per cent) continued to use the techniques in daily clinical work. Burnout was identified in 23 trainees (60.5 per cent) with no evident difference in baseline MBI scores between participants (median 4 (range 0-11) versus 5 (1-11), P = 0.770). High stress states were significantly less likely, and mindfulness significantly higher in the intervention group (P < 0.010); MBI scores were comparable before and after ESRT in the intervention cohort (P = 0.630, median 4 (range 0-11) versus 4 (1-10)). DISCUSSION: Despite arduous emergency COVID rotas ESRT was feasible and, combined with protected time for trainees to engage, deserves further research to determine medium-term efficacy.

A Systems Thinking Methodology for Studying Prevention Efforts in Communities

The turn to complexity in public health over the past 20 years has come as practitioners, policy makers and scholars lament the lack of progress in addressing wicked problems such as obesity, chronic disease and the social determinants of health. Systems science may be well suited to tackle such wicked problems. While there is a growing application of systems thinking tools and resources in public health, there are fewer examples that incorporate both systems tools and systemic inquiry processes. Prevention Tracker offered an opportunity to trial the combination of systems tools and systems thinking at the level of community chronic disease prevention efforts. Our methodology comprised four Domains of Inquiry. 1. Describing a prevention system 2. Guiding system change efforts 3. Monitoring change 4. Cross case comparison. We applied systems tools and methods to investigate each domain of inquiry such as group model building, social network analysis, graphic illustration, causal loop diagrams and system action learning. These methods were connected through the application of systemic inquiry processes that elevated the ongoing interrogation of boundary judgments, awareness of diverse and multiple perspectives, interrelationships and the importance of social learning. Prevention Tracker demonstrated that it is possible to apply a range of systems methods while also keeping focus on the overall systems science and the need for theoretical consistency. The four domains of inquiry enabled flexibility to adapt our approach in each context to learn and improve. This methodological capacity to learn and adapt may also be useful in tackling other health and social problems, such as the COVID19 pandemic. The overall findings from the study will be presented in separate publications. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.