Second-Phase Hepatitis C Plasma Viral Kinetics Directly Reflects Reduced Intrahepatic Burden of Hepatitis C Virus.

BACKGROUND: Mathematical models explain how antivirals control viral infections. Hepatitis C virus (HCV) treatment results in at least 2 phases of decline in viremia. The first phase reflects clearance of rapidly produced virions. The second phase is hypothesized to derive from loss of infected cells but has been challenging to prove. METHODS: Using single-cell methods, we quantified the number of hepatitis C virus (HCV)-infected hepatocytes in liver biopsies taken before and within 7 days of initiating direct-acting antivirals (DAAs) in a double-blinded randomized controlled trial testing 2 (sofosbuvir-velpatasvir) versus 3 (sofosbuvir-velpatasvir-voxilaprevir) DAAs. RESULTS: We employed thousands of intrahepatic measurements in 10 persons with chronic genotype 1a HCV infection: median proportion of infected hepatocytes declined from 11.3% (range, 1.3%-59%) to 0.6% (range, <0.3%-5.8%), a loss of 75%-95% infected hepatocytes. Plasma viremia correlated with numbers of HCV-infected hepatocytes (r = 0.77; P < .0001). Second-phase plasma dynamics and changes in infected hepatocytes were indistinct (P = .16), demonstrating that second-phase viral dynamics derive from loss of infected cells. DAAs led to a decline in intracellular HCV RNA and interferon-stimulated gene expression (P < .05 for both). CONCLUSIONS: We proved that second-phase viral dynamics reflect decay of intrahepatic burden of HCV, partly due to clearance of HCV RNA from hepatocytes. CLINICAL TRIALS REGISTRATION: NCT02938013.

Improving physical distancing among healthcare workers in a pediatric intensive care unit.

BACKGROUND: Healthcare workers (HCWs) not adhering to physical distancing recommendations is a risk factor for acquisition of severe acute respiratory coronavirus virus 2 (SARS-CoV-2). The study objective was to assess the impact of interventions to improve HCW physical distancing on actual distance between HCWs in a real-life setting. METHODS: HCWs voluntarily wore proximity beacons to measure the number and intensity of physical distancing interactions between each other in a pediatric intensive care unit. We compared interactions before and after implementing a bundle of interventions including changes to the layout of workstations, cognitive aids, and individual feedback from wearable proximity beacons. RESULTS: Overall, we recorded 10,788 interactions within 6 feet (∼2 m) and lasting >5 seconds. The number of HCWs wearing beacons fluctuated daily and increased over the study period. On average, 13 beacons were worn daily (32% of possible staff; range, 2-32 per day). We recorded 3,218 interactions before the interventions and 7,570 interactions after the interventions began. Using regression analysis accounting for the maximum number of potential interactions if all staff had worn beacons on a given day, there was a 1% decline in the number of interactions per possible interactions in the postintervention period (incident rate ratio, 0.99; 95% confidence interval, 0.98-1.00; P = .02) with fewer interactions occurring at nursing stations, in workrooms and during morning rounds. CONCLUSIONS: Using quantitative data from wearable proximity beacons, we found an overall small decline in interactions within 6 feet between HCWs in a busy intensive care unit after a multifaceted bundle of interventions was implemented to improve physical distancing.

The case for wearable proximity devices to inform physical distancing among healthcare workers.

OBJECTIVE: Despite the importance of physical distancing in reducing SARS-CoV-2 transmission, this practice is challenging in healthcare. We piloted use of wearable proximity beacons among healthcare workers (HCWs) in an inpatient unit to highlight considerations for future use of trackable technologies in healthcare settings. MATERIALS AND METHODS: We performed a feasibility pilot study in a non-COVID adult medical unit from September 28 to October 28, 2020. HCWs wore wearable proximity beacons, and interactions defined as <6 feet for ≥5 s were recorded. Validation was performed using direct observations. RESULTS: A total of 6172 close proximity interactions were recorded, and with the removal of 2033 false-positive interactions, 4139 remained. The highest proportion of interactions occurred between 7:00 Am-9:00 Am. Direct observations of HCWs substantiated these findings. DISCUSSION: This pilot study showed that wearable beacons can be used to monitor and quantify HCW interactions in inpatient settings. CONCLUSION: Technology can be used to track HCW physical distancing.

Nosocomial Respiratory Infections in a Rural Zambian Hospital.

The burden of nosocomial respiratory infections in rural southern Africa is poorly understood. We established a surveillance program at a rural Zambian hospital to detect influenza-like illness (ILI) and respiratory infections among hospitalized patients and a cohort of healthcare workers (HCWs). Nasopharyngeal specimens from symptomatic patients and HCWs underwent broadly multiplexed molecular testing to detect viruses and atypical bacteria. During 1 year of surveillance, 15 patients (1.7% of admissions) developed ILI more than 48 hours after admission. Among 44 HCWs, 19 (43%) experienced at least one ILI episode, with a total of 31 ILI episodes detected. Respiratory viruses were detected in 45% of patient and 55% of HCW specimens. The cumulative incidence of influenza infection among HCWs over 1 year was 9%. Overall, respiratory viruses were commonly found among patients and HCWs in a rural Zambian hospital with limited infection control infrastructure.

Reference Genome for the Highly Transformable Setaria viridis ME034V.

Setaria viridis (green foxtail) is an important model system for improving cereal crops due to its diploid genome, ease of cultivation, and use of C4 photosynthesis. The S. viridis accession ME034V is exceptionally transformable, but the lack of a sequenced genome for this accession has limited its utility. We present a 397 Mb highly contiguous de novo assembly of ME034V using ultra-long nanopore sequencing technology (read N50 = 41kb). We estimate that this genome is largely complete based on our updated k-mer based genome size estimate of 401 Mb for S. viridis Genome annotation identified 37,908 protein-coding genes and >300k repetitive elements comprising 46% of the genome. We compared the ME034V assembly with two other previously sequenced Setaria genomes as well as to a diversity panel of 235 S. viridis accessions. We found the genome assemblies to be largely syntenic, but numerous unique polymorphic structural variants were discovered. Several ME034V deletions may be associated with recent retrotransposition of copia and gypsy LTR repeat families, as evidenced by their low genotype frequencies in the sampled population. Lastly, we performed a phylogenomic analysis to identify gene families that have expanded in Setaria, including those involved in specialized metabolism and plant defense response. The high continuity of the ME034V genome assembly validates the utility of ultra-long DNA sequencing to improve genetic resources for emerging model organisms. Structural variation present in Setaria illustrates the importance of obtaining the proper genome reference for genetic experiments. Thus, we anticipate that the ME034V genome will be of significant utility for the Setaria research community.