BACKGROUND As COVID-19 disseminates throughout the US, a better understanding of patient characteristics associated with hospitalization, morbidity and mortality in diverse geographic regions is essential. METHODS Hospital chargemaster data on adult patients with COVID-19 admitted to 245 hospitals across 38 states between February 15 and April 20, 2020 were assessed. Clinical course from admission through hospitalization to discharge or death was analyzed. RESULTS A total of 11,721 patients were included (majority were >60 years of age [59.9%] and male [53.4%]). Comorbidities included hypertension (46.7%), diabetes (27.8%), cardiovascular disease (18.6%), obesity (16.1%), and chronic kidney disease (12.2%). Mechanical ventilation was required by 1,967 patients (16.8%). Mortality among hospitalized patients was 21.4% and increased to 70.5% among those on mechanical ventilation. Male sex, older age, obesity, geographic region, and the presence of chronic kidney disease or preexisting cardiovascular disease were associated with an increased odds of mechanical ventilation. All aforementioned risk factors, with the exception of obesity, were associated with an increased odds of death (all p& 0.001). Many patients received investigational medications for treatment of COVID-19, including 48 patients on remdesivir and 4,232 on hydroxychloroquine. CONCLUSION This large observational cohort describes the clinical course and identifies factors associated with outcomes of hospitalized patients with COVID-19 across the US. These data can inform strategies to prioritize prevention and treatment for this disease.

Mucin secretion in the airways of the lungs is crucial for clearance of inhaled particulates and pathogens (1). However, mucin hypersecretion is a leading cause of mortality in common diseases such as asthma and cystic fibrosis (2). Thus, tight control of mucin secretion is critical for lung homeostasis. Airway mucin secretion is stimulated by triphosphate nucleotides secreted into the extracellular lumenal liquid layer (3). These bind to epithelial apical P2Y 2 receptors that activate G q , which in turn activates phospholipase C␤ 1 generating the intracellular second messengers diacylglycerol and inositol trisphosphate (IP 3 ).3 Diacylglycerol directly induces mucin granule exocytosis by activating the priming protein Munc13-2 (4), and indirectly regulates exocytosis by activating protein kinase C⑀ (5). IP 3 induces the release of Ca 2ϩ from intracellular stores, resulting in a rise in cytoplasmic Ca 2ϩ that rapidly triggers mucin granule exocytosis (6 -9). However, the precise mechanism by which a rise in cytoplasmic Ca 2ϩ is coupled to exocytosis in goblet cells is not known.Synaptotagmins (Syts) are a family of structurally related proteins of which several are known to mediate Ca 2ϩ -dependent exocytosis. Syts are composed of a short intravesicular amino terminus, a transmembrane domain, a variable linker region, and two conserved C 2 domains near the carboxyl terminus (10, 11). There are at least 15 Syt family members encoded in mammalian genomes. Of these, eight (Syt1-3, -5-7, -9, and -10) display Ca 2ϩ -dependent phospholipid binding that is thought to be essential for Ca 2ϩ -dependent exocytosis (12-16). A subset of three of these (Syt1, -2, and -9) binds Ca 2ϩ with low affinity (ϳ10 M) and high cooperativity (n ϭ 5) and functions as fast, synchronous Ca 2ϩ sensors in neurons (16). Syt1 mediates synchronous synaptic vesicle release in forebrain neurons, and also mediates rapid exocytosis in adrenal chromaffin cells (15,16). Like neurons, chromaffin cells express voltage-gated Ca 2ϩ channels activated by neurotransmitter-induced depolarization. Syt2 mediates synchronous synaptic vesicle release in hindbrain neurons and at the neuromuscular junction (14, 17), but it has not been previously known to function outside the nervous system. Syt9 mediates synchronous synaptic vesicle release from limbic and striatal neurons (16), and it also functions in dense core granule release from the PC12 chromaffin cell line (18 -20) and insulin release from pancreatic islet cells (21,22). In islet cells, membrane depolarization and opening of voltage-gated Ca 2ϩ channels is induced by closure of K ATP channels when blood glucose is elevated. To our knowledge, there has been no analysis of the function of a low Ca 2ϩ affinity, fast Syt in a nonexcitable cell (i.e. a cell not expressing voltagegated Ca 2ϩ channels). * This work was supported, in whole or in part, by National Institutes of Health Grants HL072984, HL094848, CA105352, CA016672, and HL063756. This work was also supported by grants from the North American Cyst...

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Background Patients hospitalized for COVID-19 may experience complications following hospitalization and require readmission. This analysis estimates the rate and risk factors associated with COVID-19-related readmission and inpatient mortality. Methods This is a retrospective cohort study utilizing deidentified chargemaster data from 297 hospitals across 40 US states on patients hospitalized with COVID-19 February 15-June 09, 2020. Demographics, comorbidities, acute conditions, and clinical characteristics of first hospitalization are summarized. Mulitvariable logistic regression was used to measure risk factor associations with 30-day readmission and in-hospital mortality. Results Among 29,659 patients, 1,070 (3.6%) were readmitted. Readmitted patients were more likely to have diabetes, hypertension, cardiovascular disease (CVD), chronic kidney disease (CKD) vs those not readmitted (p<0.0001) and to present on first admission with acute kidney injury (15.6% vs. 9.2%), congestive heart failure (6.4% vs. 2.4%), and cardiomyopathy (2.1% vs. 0.8%) (p<0.0001). Higher odds of readmission were observed in patients age >60 vs. 1840 (odds ratio [OR]=1.92, 95% confidence interval [CI]=1.48, 2.50), and admitted in the Northeast vs. West (OR=1.43, 95% CI=1.14, 1.79) or South (OR=1.28, 95% CI=1.11, 1.49). Comorbidities including diabetes (OR=1.34, 95% CI=1.12, 1.60), CVD (OR=1.46, 95% CI=1.23, 1.72), CKD stage 1-5 (OR=1.51, 95% CI=1.25,1.81) and stage 5 (OR=2.27, 95% CI=1.81, 2.86) were associated with higher odds of readmission. 12.3% of readmitted patients died during second hospitalization. Conclusions Among this large US population of patients hospitalized with COVID-19, readmission was associated with certain comorbidities and acute conditions during first hospitalization. These findings may inform strategies to mitigate risks of readmission due to COVID-19 complications.