SARS-CoV-2 Morbidity and Mortality in Racial/Ethnic Minority Populations: A Window into the Stress Related Inflammatory Basis of Health Disparities.

Health disparity related to race/ethnicity has been cited as "the most serious and shameful health care issue of our time"(Peterson et al., 2018). A portion of the now recognized disproportionate impact of the COVID-19 pandemic among Black, Indigenous and People of Color (BIPOC) communities is attributable to social determinants such as socioeconomic status (SES), physical living situation, health care access, and the psychosocial factors associated with socioenvironmental circumstances such as bias, victimization, trauma and toxic stress as well as structural factors that reduce the capacity to practice physical distancing (Agurs-Collins et al., 2019). In this paper, we hypothesize that, prior to the COVID-19 pandemic, disproportionate socio-economic and environmental stressors in the BIPOC population promoted heightened stress-associated neurobiological activity (Stress-NbA). This chronic elevation in Stress-NbA results in down-stream complications of chronic stress including underactivation of anti-viral type I IFN pathway genes. This results in an increase in susceptibility to viral diseases, including coronavirus illnesses. Additionally, Stress-NbA chronically potentiates systemic inflammation (from hematopoietic system activation with myelopoiesis) increasing the prevalence of metabolic syndrome (MetS) and setting the stage for stress-related chronic non-communicable diseases (NCDs). This process was propelled by overactivation of immune cell gene expression in the nuclear factor κ-light-chain-enhancer of activated B cells (NF-kB) activation pathway and underactivation of gene expression in the anti-viral type I interferon (IFN) pathway. The higher prevalence of MetS and NCDs in minority populations turned out to be predictive of the elevated risk they would face in the presence of a highly contagious viral pandemic. The stress-related generation of a chronic non-pathogen associated molecular pattern (non-PAMP) immunoactivation state led to decreased viral immune defense and increased susceptibility to SARS-CoV-2 infection with increased risk of severe illness induced by cytokine storm syndrome (CSS).