The epidemics of HIV, sexually-transmitted diseases (STDs), hepatitis C (HCV), opioid misuse and overdose are widely recognized as a syndemic in the U.S. Access to health care services and medication assisted treatment of opioid use disorders, income inequality, housing disparities, intensity of policing activities, employment status, and healthcare policies, are all related to the prevalence of substance misuse, overdoses, infection risk and morbidity. With the COVID-19 virus overwhelmingly targeting people who would already be vulnerable to disease, it is important to also examine how it’s interaction with other epidemics may exacerbate the disease burden in certain populations and increase health vulnerability. Panelists will highlight the importance of examining and addressing structural factors, health disparities and health equity to respond to the syndemic of HIV, HCV, opioids, and COVID-19 and how structural factors are addressed through intervention and policy to reduce vulnerability of at-risk areas and populations.