# Assessing SARS-CoV-2 Variant Evolution in Patients

> **NIH NIH U19** · NORTHWESTERN UNIVERSITY · 2021 · $749,891

## Abstract

SARS-CoV-2, the cause of the COVID-19 pandemic, emerged from Wuhan, China, and rapidly spread
around the world. A feature of the pandemic has been the repeated emergence of SARS-CoV-2 clades and
variants of concern, some of which have been shown to have enhanced transmissibility. Other aspects of
these lineages, however, remain unclear. The vast majority of the 3.75 million deaths caused by SARS-CoV-2
are the result of severe pneumonia. In these patients, ongoing SARS-CoV-2 viral replication in the lungs leads
to slowly progressing pulmonary injury and subsequent respiratory failure. Yet our understanding of the genetic
evolution of SARS-CoV-2 in the lungs is limited because of difficulties sampling the pulmonary alveolar space
and in linking viral samples to robust and comprehensive clinical data. In this regard, the Successful Clinical
Response in Pneumonia Therapy (SCRIPT) Systems Biology Center provides the ideal infrastructure to collect
deep-lung viral samples and corresponding immune response and clinical metadata from patients with COVID-
19. We propose to leverage the clinical and research infrastructure of SCRIPT to study SARS-CoV-2 variants
and intra-host adaptation. We will expand SCRIPT to link patient phenotypes with virus genotypes. Our
hypothesis is that SARS-CoV-2 clades influence the severity of COVID-19 pneumonia and that viral
diversity evolves in the lungs of patients experiencing severe pneumonia. To test our hypotheses, we will
perform the following specific aims: Aim 1. We will determine whether specific SARS-CoV-2 clades are
associated with greater disease severity or altered host response. We will sequence SARS-CoV-2
isolates from a biobank of a general pool of COVID-19 patients at our institution and from BAL samples of
intubated patients with severe COVID-19 pneumonia to establish their genotypes. Associations between
specific SARS-CoV-2 clades and disease severity and outcomes in both populations will be sought. Aim 2. We
will examine the evolution of intra-host SARS-CoV-2 viral sequence changes over time in the lungs of
patients with severe COVID-19 pneumonia. In a subset of patients with prolonged respiratory failure, we will
sequence viral isolates and examine the host immune response using longitudinally collected serial BAL
samples. These data will be used to quantify viral dynamics in the lung, to map the intra-host emergence of
viral quasi-species, to characterize the host immune responses elicited by these changes, and to correlate
these features with the clinical conditions of the patients. Aim 3. We will generate a computational model
that integrates SARS-CoV-2 clade genome information with clinical and host immune response
features to predict the severity of COVID-19 infections. Viral clade data will be integrated with measures of
the host immune response (BAL fluid flow cytometry and cytokine levels) and patient clinical metadata to
develop a comprehensive model that predicts which patients will develop es...

## Key facts

- **NIH application ID:** 10426993
- **Project number:** 3U19AI135964-04S2
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ALAN R HAUSER
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $749,891
- **Award type:** 3
- **Project period:** 2021-07-29 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426993

## Citation

> US National Institutes of Health, RePORTER application 10426993, Assessing SARS-CoV-2 Variant Evolution in Patients (3U19AI135964-04S2). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10426993. Licensed CC0.

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