Gene therapy using recombinant adeno-associated virus vectors (rAAV) is generally considered safe. During the course of a study designed to determine the long-term efficacy of rAAV-mediated gene therapy initiated in newbornRecombinant adeno-associated virus (rAAV) vectors are generally considered safe. No side-effects have been reported in the many in vivo studies designed to assess the efficacy of rAAV vectors.1 Wild-type AAV (wtAAV) is not associated with any disease and the virus integrates with high frequency into a single site on human chromosome 19. However, the site specificity is lost in rAAV vectors and they have been shown to either persist as episomes or to integrate randomly into the host genome. 2-5Therefore, the potential for rAAV to have adverse sideeffects due to insertional mutagenesis may exist.In this issue of Gene Therapy, Daly et al 6 report on the long-term (1 year) efficacy of intravenous neonatal rAAV treatment for murine mucopolysaccharidosis type VII (MPSVII). Following submission of the paper, three of five rAAV-treated MPSVII mice that were part of a longevity study were killed at approximately 18 months of age for histochemical, biochemical, and histopathological analyses. All of the animals appeared healthy and the three animals killed were chosen at random. Interest-

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.

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Type I diabetes results from an autoimmune destruction of the insulin-producing pancreatic b cells. Although the exact immunologic processes underlying this disease are unclear, increasing evidence suggests that immunosuppressive, immunoregulatory and anti-inflammatory agents can interrupt the progression of the disease. Alpha 1 antitrypsin (AAT) is a multifunctional serine proteinase inhibitor (serpin) that also displays a wide range of anti-inflammatory properties. To test the ability of AAT to modulate the development of type I diabetes, we performed a series of investigations involving recombinant adeno-associated virus vector (rAAV)-mediated gene delivery of human alpha-1 antitrypsin (hAAT) to nonobese diabetic (NOD) mice. Recombinant AAV-expressing hAAT (rAAV2-CB-AT) was administered intramuscularly to 4-week-old female NOD mice (1 Â 10 10 i.u./mouse). A single injection of this vector reduced the intensity of insulitis, the levels of insulin autoantibodies, and the frequency of overt type I diabetes (30% (3/10) at 32 weeks of age versus 70% (7/10) in controls). Transgene expression at the injection sites was confirmed by immunostaining. Interestingly, antibodies against hAAT were present in a majority of the vector-injected mice and circulating hAAT was undetectable when assessed 10 weeks postinjection. This study suggests a potential therapeutic role for AAT in preventing type I diabetes as well as the ability of AAV gene therapy-based approaches to ameliorate disease effectively.

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.