Rhinovirus Infections in Hematopoietic Stem Cell Transplant Recipients with Pneumonia

Little is known about the impact of human rhinovirus (HRV) and coronavirus infections in hematopoietic stem cell transplant (HSCT) recipients. We tested bronchoalveolar lavage (BAL) samples obtained from HSCT recipients with acute pulmonary infiltrates for HRV (n = 122) and coronavirus (n = 46) by reverse-transcriptase polymerase chain reaction. HRV RNA was detected in 6 (8%) of 77 patients, and coronavirus RNA was detected in 0 of 46 of BAL samples from HSCT recipients. The fatality rate in HRV-infected patients was high (83%), but all patients had significant coinfections, and the overall mortality rate was not different from that of patients who were negative for HRV in BAL samples. These results suggest that HRV may be a cause of lower respiratory tract infections in HSCT recipients and that its detection in BAL samples is associated with frequent copathogens. Whether the poor prognosis is due to HRV or the copathogen is not clea

Assessment of Cytomegalovirus-Specific Cell-Mediated Immunity for the Prediction of Cytomegalovirus Disease in High-Risk Solid-Organ Transplant Recipients: A Multicenter Cohort Study

In high-risk solid-organ transplant recipients receiving antiviral prophylaxis, the measurement of specific cell-mediated immunity using the Quantiferon assay appropriately stratified the individual risk of developing subsequent cytomegalovirus diseas

Evaluating Methods of FAA Regulatory Compliance for Educational Use of Unmanned Aircraft Systems (UAS)

Educational institutions on all levels of the educational spectra are interested in integrating unmanned aircraft systems into their curricula; however, complex Federal Aviation Administration (FAA) regulations and potential liability issues may deter some institutions from proceeding. Using document analysis of FAA regulations, legal interpretations, and precedent, the researchers codify and compare the methods by which educational entities can legally comply with the FAA’s UAS regulations. This research overviews key issues with each method of compliance, including UAS flown as: a Public Aircraft Operation, under a Public Law 112-95 Section 333 Exemption, for hobby and recreational purposes under Public Law 112-95 Section 336 Model Aircraft Rules, and in compliance with the newly released 14 CFR Part 107 Regulations. The researchers present a recommended decision matrix for educational entities to evaluate their individual operational needs and select the most appropriate method of regulatory compliance for UAS integration. Additionally, the researchers present a proposed framework for an institutional review committee to evaluate and safely implement UAS operations at educational campuses

Clinical Experience in Adults and Children Treated with Intravenous Peramivir for 2009 Influenza A (H1N1) Under an Emergency IND Program in the United States

Peramivir, an investigational intravenous neuraminidase inhibitor, was given to 31 hospitalized patients with severe viral pneumonia during the 2009 H1N1 influenza pandemic under the Emergency IND regulations. The drug was generally well tolerated and associated with recovery in most patientes

Characterization of Oseltamivir-Resistant 2009 H1N1 Pandemic Influenza A Viruses

Influenza viruses resistant to antiviral drugs emerge frequently. Not surprisingly, the widespread treatment in many countries of patients infected with 2009 pandemic influenza A (H1N1) viruses with the neuraminidase (NA) inhibitors oseltamivir and zanamivir has led to the emergence of pandemic strains resistant to these drugs. Sporadic cases of pandemic influenza have been associated with mutant viruses possessing a histidine-to-tyrosine substitution at position 274 (H274Y) in the NA, a mutation known to be responsible for oseltamivir resistance. Here, we characterized in vitro and in vivo properties of two pairs of oseltaimivir-sensitive and -resistant (possessing the NA H274Y substitution) 2009 H1N1 pandemic viruses isolated in different parts of the world. An in vitro NA inhibition assay confirmed that the NA H274Y substitution confers oseltamivir resistance to 2009 H1N1 pandemic viruses. In mouse lungs, we found no significant difference in replication between oseltamivir-sensitive and -resistant viruses. In the lungs of mice treated with oseltamivir or even zanamivir, 2009 H1N1 pandemic viruses with the NA H274Y substitution replicated efficiently. Pathological analysis revealed that the pathogenicities of the oseltamivir-resistant viruses were comparable to those of their oseltamivir-sensitive counterparts in ferrets. Further, the oseltamivir-resistant viruses transmitted between ferrets as efficiently as their oseltamivir-sensitive counterparts. Collectively, these data indicate that oseltamivir-resistant 2009 H1N1 pandemic viruses with the NA H274Y substitution were comparable to their oseltamivir-sensitive counterparts in their pathogenicity and transmissibility in animal models. Our findings highlight the possibility that NA H274Y-possessing oseltamivir-resistant 2009 H1N1 pandemic viruses could supersede oseltamivir-sensitive viruses, as occurred with seasonal H1N1 viruses

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID‐19 during the course of the pandemic

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations