# Multimodal immune profiling to determine mechanisms of COVID-19 clinical trajectory in Uganda

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $208,408

## Abstract

PROJECT SUMMARY
The COVID-19 pandemic is the greatest global health crisis in over a century. In high-income countries (HICs),
outcomes for patients with severe COVID-19 have improved markedly over the past 18 months due to provision
of high-quality critical care and administration of immunomodulatory agents such as corticosteroids and
interleukin-6 antagonists. Effective use of these therapeutic agents was driven by translational investigations
that identified dysregulated immune-inflammatory responses as key pathological features in severe COVID-19.
Following advances in COVID-19 prevention in HICs, the pandemic burden has shifted to low- and middle-
income countries, which now account for >40% of daily mortality related to COVID-19. This burden is particularly
severe in sub-Saharan Africa (SSA), where recurrent COVID-19 surges have overwhelmed fragile health
systems and case fatality rates are among the highest in the world. Although the immunological context of
COVID-19 in SSA is unique due to high HIV burden and the relatively young age of hospitalized adults, among
other factors, little is known about the immunopathology of severe COVID-19 in the region. Through an
established collaboration between Columbia University and Uganda Virus Research Institute, we have
prospectively enrolled over 400 patients with COVID-19 in Uganda across the entire spectrum of illness severity.
Leveraging this unique cohort, the overall goal of this study is to determine biological mechanisms of COVID-19
clinical severity in Uganda using a multimodal approach to host immune profiling. We will determine the
relationship between soluble immune biomarkers and severe-critical illness among adults with COVID-19 in
Uganda using minimally-biased machine learning methods (Aim 1); identify biological pathways and immune cell
profiles associated with severe-critical COVID-19 in Uganda using whole-blood RNA sequencing data (Aim 2);
and integrate biomarker and RNA-sequencing data to determine the effect of HIV-infection on innate and
adaptive immune responses in COVID-19 (Aim 3). Directly addressing NIH COVID-19 research priorities, our
results will (i) advance fundamental understanding of the immunopathological mechanisms driving the burden of
severe COVID-19 in SSA and other vulnerable, high HIV burden settings, and (ii) classify patients with COVID-
19 into biologically-driven and clinically-meaningful subgroups for whom locally-responsive treatment strategies
can be more precisely investigated and developed.

## Key facts

- **NIH application ID:** 10508523
- **Project number:** 1R21AI171249-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Matthew John Cummings
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $208,408
- **Award type:** 1
- **Project period:** 2022-06-23 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10508523

## Citation

> US National Institutes of Health, RePORTER application 10508523, Multimodal immune profiling to determine mechanisms of COVID-19 clinical trajectory in Uganda (1R21AI171249-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10508523. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*