Alcohol, nicotine, and COVID-19: A retrospective study of health outcomes in central Pennsylvania.

Individuals with substance abuse disorder are at increased risk for the development of severe disease following COVID-19 infection. Furthermore, individuals in rural populations where access to healthcare is limited and rates of substance abuse tend to be higher are at increased risk compared to other regions. The Penn State Health Network serves 29 counties in central Pennsylvania that are largely rural. The current study assessed the electronic medical records for individuals in this population that were reported as having alcohol dependence, nicotine dependence or both (co-users) in addition to individuals with no history of drug use and the rate of developing primary and secondary health outcomes following COVID-19 infection. All patients in this study were determined to be COVID+ while in care. We found that overall, risk for requiring ventilation, developing pneumonia, and mortality within 30 days of diagnosis all increased with any substance use history, across both males and females and across all age groups. Moreover, rates of these outcomes were considerably higher in patients that were both alcohol and nicotine dependent suggesting additive effects of co-use. Rates of secondary effects also increased substantially across all use categories with these patients showing greater risk of developing liver, kidney, and pancreas maladies compared to patients with no history of substance use. Taken together, these findings reinforce previous studies showing that substance use increases the risks of significant disease following COVID-19 infection, giving insights into the health disparities that exist in rural populations.

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.

Vascular dysfunction promotes regional hypoxia after bevacizumab therapy in recurrent glioblastoma patients.

BACKGROUND: Hypoxia is a driver of treatment resistance in glioblastoma. Antiangiogenic agents may transiently normalize blood vessels and decrease hypoxia before excessive pruning of vessels increases hypoxia. The time window of normalization is dose and time dependent. We sought to determine how VEGF blockade with bevacizumab modulates tumor vasculature and the impact that those vascular changes have on hypoxia in recurrent glioblastoma patients. METHODS: We measured tumor volume, vascular permeability (Ktrans), perfusion parameters (cerebral blood flow/volume, vessel caliber, and mean transit time), and regions of hypoxia in patients with recurrent glioblastoma before and after treatment with bevacizumab alone or with lomustine using [18F]FMISO PET-MRI. We also examined serial changes in plasma biomarkers of angiogenesis and inflammation. RESULTS: Eleven patients were studied. The magnitude of global tumor hypoxia was variable across these 11 patients prior to treatment and it did not significantly change after bevacizumab. The hypoxic regions had an inefficient vasculature characterized by elevated cerebral blood flow/volume and increased vessel caliber. In a subset of patients, there were tumor subregions with decreased mean transit times and a decrease in hypoxia, suggesting heterogeneous improvement in vascular efficiency. Bevacizumab significantly changed known pharmacodynamic biomarkers such as plasma VEGF and PlGF. CONCLUSIONS: The vascular signature in hypoxic tumor regions indicates a disorganized vasculature which, in most tumors, does not significantly change after bevacizumab treatment. While some tumor regions showed improved vascular efficiency following treatment, bevacizumab did not globally alter hypoxia or normalize tumor vasculature in glioblastoma.