Immune correlates of long-term success with DAA therapy in HCV/HIV infected people who inject drugs

Risk factors for developing severe illness/acute respiratory distress syndrome from coronavirusdisease 2019 (COVID-19) include older age, male gender, and underlying conditions, currentlyidentified as smoking, chronic lung disease or moderate to severe asthma, heart disease withcomplications, severe obesity, diabetes, renal failure or liver disease. Immune factors are likelyto contribute to disease progression. While immune activation is required for anti-viral response,severely ill patients show an excessive and aberrant host immune response as evidenced by highinflammatory markers and proinflammatory cytokines. On the other hand, factors associatedwith less robust immune response against the virus, such as advanced age are associated withsevere disease. Opioid use disorder (OUD) is an important public heath condition associated withdysregulated immunity. This may be related to higher prevalence of systemic comorbidconditions and concomitant conditions like chronic HIV, hepatitis C or incident infectionsrelated to injection drug use, which may further influence immune response to infections. Anespecially vulnerable group is people living with HIV (PLWH) with OUD, which are expected tohave further immune dysregulations due to twin effect of HIV and opioids on immunity.Additionally, people with OUD are at increased risk of COVID-19 due to social factors suchas homelessness, poor access to healthcare, housing insecurity, greater likelihood ofincarceration, which can make it more difficult to maintain social distancing and theseindividuals may not seek medical care promptly due to lack of access to outpatient care. We areasking whether OUD constitutes a risk factor for progressive (COVID-19), especially in PLWH.We are investigating immune responses in individuals with OUD and HIV infection under ourNIDA funded R01; leveraging the clinical cohorts and IRB approved blood collection protocolsfrom COVID-19 patients, here we will investigate incidence and progression of COVID-19 inthese patient populations. First, we will document clinical course and outcomes of COVID-19 inpatients with or without OUD/HIV. To identify immune correlates of COVID-19 severity, wewill perform analysis of B and T cell responses and study impact of OUD and HIV on thisresponse. Our investigation of clinical and immunological features of the disease in PLWH andOUD will expand on known correlates of progressive COVID-19 and will inform treatment andprophylactic approaches for COVID-19 in vulnerable groups.