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.
