First 12 patients with coronavirus disease 2019 (COVID-19) in the United States

IntroductionMore than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. MethodsWe collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. ResultsAmong the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. ConclusionsIn 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

Effect of Na/Ca exchange on plateau fraction and [Ca]i in models for bursting in pancreatic beta-cells.

In the presence of an insulinotropic glucose concentration, beta-cells, in intact pancreatic islets, exhibit periodic bursting electrical activity consisting of an alternation of active and silent phases. The fraction of time spent in the active phase over a period is called the plateau fraction and is correlated with the rate of insulin release. However, the mechanisms that regulate the plateau fraction remain unclear. In this paper we investigate the possible role of the plasma membrane Na+/Ca2+ exchange of the beta-cell in controlling the plateau fraction. We have extended different single-cell models to incorporate this Ca2+-activated electrogenic Ca2+ transporter. We find that the Na+/Ca2+ exchange can provide a physiological mechanism to increase the plateau fraction as the glucose concentration is raised. In addition, we show theoretically that the Na+/Ca2+ exchanger is a key regulator of the cytoplasmic calcium concentration in clusters of heterogeneous cells with gap-junctional electrical coupling.

Significance of Na/Ca exchange for Ca2+ buffering and electrical activity in mouse pancreatic beta-cells.

We have combined the patch-clamp technique with microfluorimetry of the cytoplasmic Ca2+ concentration ([Ca2+]i) to characterize Na/Ca exchange in mouse beta-cells and to determine its importance for [Ca2+]i buffering and shaping of glucose-induced electrical activity. The exchanger contributes to Ca2+ removal at [Ca2+]i above 1 microM, where it accounts for >35% of the total removal rate. At lower [Ca2+]i, thapsigargin-sensitive Ca2+-ATPases constitute a major (70% at 0.8 microM [Ca2+]i) mechanism for Ca2+ removal. The beta-cell Na/Ca exchanger is electrogenic and has a stoichiometry of three Na+ for one Ca2+. The current arising from its operation reverses at approximately -20 mV (current inward at more negative voltages), has a conductance of 53 pS/pF (14 microM [Ca2+]i), and is abolished by removal of external Na+ or by intracellularly applied XIP (exchange inhibitory peptide). Inhibition of the exchanger results in shortening (50%) of the bursts of action potentials of glucose-stimulated beta-cells in intact islets and a slight (5 mV) hyperpolarization. Mathematical simulations suggest that the stimulatory action of glucose on beta-cell electrical activity may be accounted for in part by glucose-induced reduction of the cytoplasmic Na+ concentration with resultant activation of the exchanger.

Optimizing sodium balance in hemodialysis.

this paper develops and tests a mathematical model for Na+ kinetics applied to standard hemodialysis. The volume of distribution of exchangeable Na+, dialyzer surface area, blood and dialysis fluid flow rate, target weight loss, treatment duration and the Na+ diffusibility constant are taken into account. The model is used to compute the optimal hour by hour dialysis fluid Na+ concentration required to achieve the prescribed end-dialysis natremia and maintain a constant end-dialysis body Na+ pool, while providing a nearly uniform removal of Na+ over dialysis. The model was preliminary tested on 10 consecutive dialyses in a single patient using special dialyzer which generates a part of ultrafiltrate uncontaminated by dialysate.

Modelling nonlinear integration of synaptic signals by neurones.

Neurones with active conductance on dendrites integrate synaptic signals and modulate generation of axon spikes in a nonlinear way. Owing to experimental difficulties, modelling provides invaluable insight for the comprehension of neurone behaviour particularly when dendrites are excitable. We used experimental data obtained for the Anterior Gastric Receptor neurone (AGR neurone), which controls the lobster gastric mill activity, to derive a set of partial differential equations for the membrane voltage. Simulation showed that upon varying the intensity of stimulation on the dendrite, the response pattern between dendrites and axon activity continuously changes. In addition, when only half of the dendritic tree is active, axon firing exhibits regular oscillations and bursting activity. We discuss these results in relation with the experimental work done on the AGR neurone.