ABSTRACT
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.
ABSTRACT
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.