# Uncover mechanisms underlying the development of chronic lung sequelae post COVID-19

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $662,044

## Abstract

Project Summary
Apart from the acute illness caused by SARS-CoV-2, it is now clear that a significant percentage of patients
develop long-term conditions post COVID-19, including systemic and respiratory symptoms. Given the
catastrophic spread of SARS-CoV-2 infection globally, there are many individuals that recover from acute
COVID-19 and develop permanent impairment in lung function which can cause exertional dyspnea, fatigue (due
to chronic hypoxia), and other limitations. This number will become even larger as the pandemic continues to
progress.
Therefore, there is an urgent need to understand the mechanisms underlying the development of
chronic respiratory sequelae of COVID-19 to develop
preventive and therapeutic interventions.
In this application, we aim to unravel the driving mechanisms and identify potential therapeutic targets of chronic
lung sequelae following COVID-19. To achieve this goal, we propose two Specific Aims (SA) for the study. SA
1. Decipher cellular and molecular traits underlying chronic lung sequelae post-acute COVID-19.
We will
enroll
 a group of COVID-19 convalescents that are expected to develop chronic lung sequelae after prior severe
acute disease and a control population that completely recovered from previous mild or non-symptomatic
COVID-19 infection. We will conduct comprehensive clinical examination supplemented by quantitative chest
CT imaging and pulmonary function testing to determine clinical and pathophysiological characteristics of the
two populations. We will collect longitudinal blood and bronchoalveolar lavage fluid (BAL) to obtain immune,
molecular, and viral profiles in COVID-19 convalescents and controls. This unique approach integrating
systemic and respiratory clinical, pathophysiological, cellular, molecular, and viral profiles of control or COVID-
19 convalescents will be highly compelling for future druggable target discovery. SA2. Model and validate
targets of chronic lung sequelae post-acute COVID-19 in an animal model. We will establish a mouse model
of chronic lung sequelae post-acute COVID-19. We will characterize systemic and respiratory host cellular and
molecular responses in the model. integrate mouse and human data for
validation of mechanistic links and discovery of new insights and/or targets for therapeutic interventions. We will
then use the model to test whether target dysregulated respiratory CD8+ T cell responses could ameliorate
chronic lung sequelae post-acute COVID-19.
We will employ system biology tools to
The successful completion of the study will generate unprecedented insights on clinical, viral, and immune traits
of pulmonary sequelae, and will identify key causal immune mechanisms and therapeutic targets against chronic
lung diseases post-acute COVID-19.

## Key facts

- **NIH application ID:** 10894885
- **Project number:** 5R01HL170961-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jie Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $662,044
- **Award type:** 5
- **Project period:** 2023-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894885

## Citation

> US National Institutes of Health, RePORTER application 10894885, Uncover mechanisms underlying the development of chronic lung sequelae post COVID-19 (5R01HL170961-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10894885. Licensed CC0.

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