Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single-cell transcriptomics

SARS-COV-2 and the associated respiratory disease, COVID-19, has been linked to over 100,000 deathsglobally since fall of 2019. Severe COVI9 and associated mortality has strongly been correlated withseveral comorbidities including age, diabetes, immunodeficiencies and cardiovascular diseases. Howbehavioral or lifestyle factors, in particular tobacco use, influence the course of COVID19 has not beendirectly examined. Tobacco use, smoking and vaping, is a particular concern since it is directly linked topoor lung health and increased susceptibility to bacterial and viral pulmonary infections including SARSand MERS coronaviruses. Furthermore, patients that use tobacco products are at higher risk for thecomorbidities such as, diabetes and cardiovascular diseases that are risk factors for COVID19. SARS-COV2 infection and tobacco use both trigger and perpetuate a dysfunctional inflammatory cytokineresponse in the lung. We hypothesize that smoking and vaping are primary risk factors associatedwith severe COVID19 and that they directly contribute to morbidity and mortality by exacerbatingthe uncontrolled pulmonary cytokine storm.We will adapt transcriptomics approaches established for our current R61, "Effect of Opioid Use Disorderon HIV Latent Reservoirs and Immune Dysfunction Assessed by Single-Cell Transcriptomics" to gaininsights into COVID19 mechanism of disease. We will initially obtain blood samples from the BostonMedical Center COVID19 biorepository collected from COV19+ smokers and nonsmokers and compare toCOV19-negative individuals and perform state of the art digital drop single cell RNA sequencing, singlecell ATAC-sequencing and computational analysis to provide insights into key innate immune signaturesthat directly contribute to COVID19. Although we will initially focus on blood since this is an easilyobtainable tissue and often provides an immunological footprint of disease, we will compare blood withother clinical tissue samples including lung fluids as they become available.The completion of these studies will provide new insights into COVID19 biomarkers and dysregulation ofspecific inflammatory pathways. A primary goal is to use the results from these proposed experiments togenerate new hypotheses that will guide more mechanistic studies towards understanding epigeneticevents that directly and indirectly influence the course of pulmonary lung infections.