PROJECT SUMMARY
SARS-CoV-2 is a novel coronavirus which causes COVID-19, a disease that has infected >46M people resulting
in >1.2M deaths by 31 October 2020. The US has the highest global case count (>9.2M) and mortality (>230K)
with recent record-setting daily cases and hospitalization rates across the country. This has been particularly
true for New Mexico (NM) where cases and hospitalizations are surging again. It is now recognized that certain
minority groups, i.e., African Americans, Hispanics, and American Indians/Alaska Natives (AI/AN), suffer
disproportionally from COVID-19. NM has the highest proportion of Hispanic ancestry, and one of the largest
AI/AN populations, with these two groups representing 47% and 26% of the cumulative cases, respectively. After
adjusting for population size, the AI/AN group has 3.3-fold higher cumulative case rates, 7.9-fold higher
hospitalizations, and 10.6-fold higher age-adjusted mortality rates. As the only academic medical center and
Level 1 Trauma Center in the state, the University of New Mexico Hospital (UNMH) has played a principal role
in caring for patients with COVID-19. UNMH is the primary tertiary care referral center for NM and surrounding
regions, including the Navajo Nation and other tribal lands. As such, we are uniquely positioned to address
important gaps-in-knowledge about the molecular basis of increased COVID-19 disease severity and mortality
in disproportionally affected ancestral groups. In mid-February, the UNM Center for Global Health assembled a
multidisciplinary group of investigators to address the challenges of COVID-19. As of 31 October, we have
recruited and followed 167 hospitalized patients with COVID-19, offering an opportunity for rapid translational
impact within the planned three-year study. The experimental strategy parallels our ongoing R01 studies in
African children utilizing mRNA-Seq to identify novel therapeutic targets (PI: Perkins). State-of-the-art
methodologies and modeling efforts in place in our laboratories will be applied to create solutions for improving
outcomes in COVID-19 patients. This will be achieved by following non-severe and severe COVID-19 patients
across hospitalization from different ancestral groups to successfully complete three specific aims: 1) determine
the impact of SARS-CoV-2 viral load dynamics on disease severity, 2) identify gene expression networks that
mediate disease severity, and 3) identify prioritized FDA-approved compounds that modulate gene networks
associated with enhanced disease severity for use in future clinical trials. In a short time, we have generated
extensive data on viral load dynamics and identified novel gene networks with target-compound matches. We
present data showing that individuals of AI/AN descent have significantly higher and protracted viral loads in
peripheral blood and more severe disease, despite comparable co-morbid factors with other groups. The
proposed investigations have direct translational impact, particularly in disproportionately affected ancestral
groups by defining the host immune response to SARS-CoV-2, identifying biomarkers for risk assessment,
prognosis, and disease progression, and fostering drug repurposing to reduce disease severity and mortality.
