The effect of TRV027 on coagulation in COVID 19: A pilot randomized, placebo-controlled controlled trial.

COVID-19 causes significant thrombosis and coagulopathy, with elevated D-dimer a predictor of adverse outcome. The precise mechanism of this coagulopathy remains unclear, one hypothesis is that loss of Angiotensin Converting Enzyme 2 activity during viral endocytosis leads to pro-inflammatory angiotensin II accumulation, loss of angiotensin-1-7 and subsequent vascular endothelial activation. We undertook a double blind randomised, placebo controlled experimental medicine study to assess the effect of TRV027, a synthetic angiotensin-1-7 analogue on D-dimer in 30 patients admitted to hospital with COVID-19 (REC ref. 20/HRA/3414), Clinical Trial No. NCT04419610. The study showed a similar rate of adverse events in TRV027 and control groups. There was a numerical decrease in D-dimer in the TRV027 group and increase in D-dimer in the placebo group, however, this did not reach statistical significance (p=0.15). A Bayesian analysis demonstrated there was a 92% probability that this change represented a true drug effect.

Estimating the Nosocomial Transmission Rate of COVID-19 in Orthopaedic Surgery Patients During the Peak of the Pandemic

Purpose To estimate the risk of hospital-acquired COVID-19 transmission in a population of orthopaedic trauma patients during the first wave of the pandemic. Patients and Methods This is a retrospective cohort study of 109 patients who underwent an emergent orthopedic procedure by a single orthopedic traumatologist between March 1, 2020 and May 15, 2020 during the first peak of the pandemic. After applying inclusion and exclusion criteria, a total of 82 patients (67 inpatients and 15 ambulatory) were identified for final analysis. The primary outcome measured was postoperative Coronavirus (COVID-19) status. Secondary outcome measures included length of stay and discharge disposition. Results The mean age and length of stay in the hospital group was 59.5 years (± 21.7) and 4.3 days (± 4.6), respectively, versus 47.9 years (± 9.8) in the ambulatory group. 7.3% (6/82) of the inpatients subsequently tested or screened positive for COVID-19 at 2 weeks post-operatively, compared to 0/15 ambulatory patients (P=0.58). Of the 6 inpatients who tested positive, 4 (66.7%) were discharged to a rehabilitation center. Diabetes (P=0.05), hypertension (P=0.02), and congestive heart failure (P=0.005) were associated with transmission. Conclusion In this analysis, there was a nosocomial transmission rate of 7% compared to zero in the ambulatory surgery center, however this was not found to be statistically significant. This data supports the use of precautions such as frequent screening, hand washing, and masks to reduce transmission when COVID-19 rates are high. There is a lower risk of nosocomial COVID-19 transmission for patients treated as an outpatient and elective surgical procedures may be safer in this setting.

Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections.

Zoonotic pathogens, such as COVID-19, reside in animal hosts before jumping species to infect humans. The Carnivora, like mink, carry many zoonoses, yet how diversity in host immune genes across species affect pathogen carriage is poorly understood. Here, we describe a progressive evolutionary downregulation of pathogen-sensing inflammasome pathways in Carnivora. This includes the loss of nucleotide-oligomerization domain leucine-rich repeat receptors (NLRs), acquisition of a unique caspase-1/-4 effector fusion protein that processes gasdermin D pore formation without inducing rapid lytic cell death, and the formation of a caspase-8 containing inflammasome that inefficiently processes interleukin-1ß. Inflammasomes regulate gut immunity, but the carnivorous diet has antimicrobial properties that could compensate for the loss of these immune pathways. We speculate that the consequences of systemic inflammasome downregulation, however, can impair host sensing of specific pathogens such that they can reside undetected in the Carnivora.

That Really Escalated Quickly—Online Learning Moves Into the Mainstream: Introduction to the Special Issue

Early in 2020, it became clear the COVID-19 pandemic was on its way toward disrupting the status quo in education in a substantial manner. As schools reacted by moving teaching and learning online, teachers, staff, parents, students, and other stakeholders were thrust into a world of learning previously discussed in this journal, but unknown to most in the field of special education. In this introduction to the special issue on online learning, we highlight key themes across the six articles, as well as lay out a vision for additional research and development that is required in our field.

Cells of the adult human heart.

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.