Tremblay and colleagues asked whether patients receiving either routine anticoagulation or antiplatelet therapy for existing conditions prior to becoming ill with COVID-19 have different outcomes from patients receiving neither therapy. After matching for existing comorbidities, this retrospective observational study finds no evidence for an effect of prediagnosis anticoagulation on mortality.

Observational data suggest an acquired prothrombotic state may contribute to the pathophysiology of COVID-19. These data include elevated D-dimers observed among many COVID-19 patients. We present a retrospective analysis of admission D-dimer, and D-dimer trends, among 1065 adult hospitalized COVID-19 patients, across 6 New York Hospitals. The primary outcome was all-cause mortality. Secondary outcomes were intubation and venous thromboembolism (VTE). Three-hundred-thirteen patients (29.4%) died, 319 (30.0%) required intubation, and 30 (2.8%) had diagnosed VTE. Using Cox proportional-hazard modeling, each 1 μg/ml increase in admission D-dimer level was associated with a hazard ratio (HR) of 1.06 (95%CI 1.04–1.08, p < 0.0001) for death, 1.08 (95%CI 1.06–1.10, p < 0.0001) for intubation, and 1.08 (95%CI 1.03–1.13, p = 0.0087) for VTE. Time-dependent receiver-operator-curves for admission D-dimer as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.694, 0.621, and 0.565 respectively. Joint-latent-class-modeling identified distinct groups of patients with respect to D-dimer trend. Patients with stable D-dimer trajectories had HRs of 0.29 (95%CI 0.17–0.49, p < 0.0001) and 0.22 (95%CI 0.10–0.45, p = 0.0001) relative to those with increasing D-dimer trajectories, for the outcomes death and intubation respectively. Patients with low-increasing D-dimer trajectories had a multivariable HR for VTE of 0.18 (95%CI 0.05–0.68, p = 0.0117) relative to those with high-decreasing D-dimer trajectories. Time-dependent receiver-operator-curves for D-dimer trend as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.678, 0.699, and 0.722 respectively. Although admission D-dimer levels, and D-dimer trends, are associated with outcomes in COVID-19, they have limited performance characteristics as prognostic tests.

Protein kinase B/Akt is a key signaling molecule that regulates cell survival, growth, and metabolism, and inhibits apoptosis. Traumatic brain injury (TBI) activates Akt, and Akt has been implicated in neuronal survival after TBI, but little is known about injury-induced Akt activation in astrocytes, cells that exhibit hypertrophic and hyperplastic responses to CNS injury. Here we have investigated the effect of mechanical strain on Akt activation in primary cultures of rat cortical astrocytes growing on deformable Silastic membranes. When astrocytes were subjected to mechanical strain (50 msec; 5-7.5 mm displacement), we observed an increase in phosphorylation of serine 473, a key indicator of Akt activation. Akt phosphorylation was increased at 3 min postinjury, was maximal from 5 to 10 min, and declined gradually thereafter. Akt activation was also dependent on the severity of the injury. Stretch-induced Akt phosphorylation was attenuated by blocking calcium influx and phosphoinositide 3-kinase (PI3K), an upstream activator of Akt. In addition, we found that ATP is rapidly released after mechanical strain and that the P2 purinergic receptor antagonist iso-pyridoxal-5'-phosphate-6-azophenyl-2',5'disulfonate (PPADS) attenuated trauma-induced Akt activation. We conclude that mechanical strain causes activation of Akt in astrocytes via stimulation of P2 receptors. This suggests that P2 receptor/Akt signaling promotes astrocyte survival and growth, and this process may play a role in the generation of reactive gliosis after TBI.

Introduction: A hyperinflammatory environment has been a hallmark of COVID-19 infection and is thought to be a key mediator of morbidity. Elevated ferritin has been observed in many patients with COVID-19. Several retrospective studies have shown ferritin levels can be correlated and predictive of poor outcomes in COVID-19, though a rigorous analysis has been lacking. Methods: A retrospective analysis of 942 adult COVID-19 patients admitted in March 2020 at a large New York City health system with available ferritin levels.