SARS-CoV-2 and Social Determinants of Health Impact on Inflammation Associated Depression Risk (SSIDR)

PROJECT SUMMARY A Global Burden Disease survey commissioned by the World Health Organization (WHO) estimated a 27.6% increase in cases of major depressive disorder (MDD) during the COVID-19 pandemic, particularly among specific vulnerable groups including healthcare workers (HCW), those with pre-existing medical/mental health conditions, as well as ethnic minority communities, many of whom may have their wellbeing challenged from additional stressors compounded by negative social determinants of health (SDOH). Recent findings from the EMBARC study have shown that small lipid molecules called eicosanoids, which act as both activators and suppressors of inflammatory activity as well as modulators of innate and adaptive immunity, are known to have a significant impact on the subacute and chronic sequelae of SARS-CoV-2, in addition to risk for unresolved immune-mediated inflammatory conditions such as CVD. Eicosanoids have also been found to be a contributor of chronic neuroinflammatory conditions such as depression in other studies. Advanced mass spectrometry methods now allow for the rapid and accurate quantification of hundreds of upstream eicosanoid mediators representing multiple enzymatic origins. Hence, this proposal aims to provide a more detailed understanding of how upstream eicosanoid pathways can be variably active, imbalanced, and perturbed in relation to an individual's propensity for developing depression. We will leverage the expertise of an interprofessional team, including current members of the EMBARC research study team, to test the hypothesis that: 1) SARS-CoV-2 infection and reinfections moderate development of chronic immune-mediated neuroinflammatory condition such as depression as evidenced by changes in eicosanoid profiles; and 2) health impacts of SDOH compounds depression risk following SARS-CoV-2 infection and reinfection by moderating the neuroimmune-inflammatory response. We propose a systematic approach to comprehensively investigating the components of upstream inflammatory activity in relation to outcomes across the spectrum of depression risk through the collection of longitudinal (survey, clinical, biomarker) data from a large and diverse population of people already enrolled in the EMBARC research study and will use a variety of methods (e.g., eicosanoid profiling, use of public available health equity data set) to assess SARS-CoV-2 infection and the SDOH impact on neuroinflammation that is associated with depression. This work will pave the way for follow-up studies investigating the efficacy of anti- inflammatory therapies, including both existing and novel agents, for modulating variation in distinct eicosanoids and, in turn, mental health outcomes such as depression.