# BIOREPOSITORY OPTIMIZATION AND USE FOR ENDOTYPING CRITICALLY ILL SARS-COV-2 INFECTED PATIENTS

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $252,467

## Abstract

Abstract. The New York City area has faced a surge of cases early on the COVID-19 pandemic in the United
States leading to destabilization of multiple health care systems that could not keep up with the high demand for
critical care use and mortality. The heterogenous evolution among critically ill COVID-19 patients, high mortality
and prolonged ICU stay highlights the need to better understand individual’s endotype that could expose
treatable traits among these septic patients. As the first set of cases arrived to NYU, we built a biorepository of
samples from the lower airways and blood from these critically-ill SARS-CoV-2 infected patients. We have
already explored the lower airway microbial environment including the virome, bacteriome and host immune
response. In our recent report using cross sectional lower airway samples from 142 critically ill COVID-19
patients published in Nature Microbiology we identified microbial and host signatures associated with poor
outcome, predominantly driven by poorly controlled viral replication, blunted anti-Spike/anti-RBD IgG response
and distinct host transcriptomic profile. However, in order to understand the mechanism underlying this poor viral
control we need to study samples at earlier time points and longitudinally. We are currently using these samples
to characterize the longitudinal viral and host transcriptome dynamics. However, the critical molecular immune
mediators need to be explored using metabolomic approaches while the distinct cellular immune responses may
require single cell approaches. In this application we will use our existing biorepository and expand it with new
cases to test the hypothesis that airway and systemic endotyping with novel scRNA sequencing and
metabolomic approaches predicts poor outcome in critically ill SARS-CoV-2 patients. Thus, we propose to
expand and optimize our biorepository of airway and systemic samples in critically ill SARS-CoV-2 patients (R21
phase) in order to perform scRNA sequencing and metabolomic approaches in order to endotype the airway
and systemic environment to evaluate for associations with poor clinical outcome (R33 phase). To accomplished
these aims we will use our expertise in the characterization of the lower airway microbiome (including the viral
fraction) and the host immune profile. Therefore, this is an unprecedented opportunity to conduct the necessary
exploratory investigations on paired lower airway and systemic samples from critically ill COVID-19 patients.
Lay summary. Acute COVID-19 infection has had unprecedented effects on human health with critically ill
patients suffering high critical care resources and mortality. In this project, we will use and expand our
biorepository of lower airway and blood samples to explore novel ways to determine molecular signatures that
can predict patients’ poor clinical outcomes.

## Key facts

- **NIH application ID:** 10510084
- **Project number:** 1R21GM147800-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Leopoldo Nicolas Segal
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $252,467
- **Award type:** 1
- **Project period:** 2022-08-16 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510084

## Citation

> US National Institutes of Health, RePORTER application 10510084, BIOREPOSITORY OPTIMIZATION AND USE FOR ENDOTYPING CRITICALLY ILL SARS-COV-2 INFECTED PATIENTS (1R21GM147800-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10510084. Licensed CC0.

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