# Sex, obesity, immunometabolism, and viral persistence in post-acute sequelae of SARS-CoV-2 infection

> **NIH NIH U19** · JOHNS HOPKINS UNIVERSITY · 2022 · $1,209,546

## Abstract

Summary
After SARS-CoV-2 infection, a significant percentage of people develop persistent symptoms or health
complications, often referred to as ‘long COVID’ or post-acute sequelae of COVID-19 (PASC). The host, virus
and environmental factors affecting the development of PASC are not well known, which hinders development
of therapeutics for patients. There also are no biomarkers for PASC, which complicates development of
diagnostics. In the proposed work, we will build on preliminary data showing immune and metabolic
dysregulation correlating with specific symptoms of PASC. We have assembled a cross-disciplinary
collaborative team with global expertise in SARS-CoV-2 virology, viral immunity, RNA virus persistence, cutting
edge tissue-based viral assays, animal models of COVID-19, cohort methodology, infectious diseases
diagnostics, high-dimensional single cell data analysis, and sex-based differences in respiratory viral infection.
Our team includes the primary investigators of an NIH-funded COVID-19 Serology Center of Excellence and
four large COVID-19 clinical studies with > 1500 enrolled participants and longitudinal blood and respiratory
mucosal sampling coupled with symptom surveys from 2 days after symptom onset through 18 months after
symptom onset. We will study the intersection of persistent viral antigen or RNA, host immune response, sex,
obesity, and PASC. Our central hypothesis is that distinct and persistent immune metabolic profiles are
associated with specific post-COVID conditions. In Aim 1, we will use immune-metabolic high-dimensional flow
cytometry, targeted metabolic gene expression profiling and functional assays, and single cell RNA sequencing
to dissect the metabolic and immune programs driving differentiation and function of these unique populations
in longitudinal samples from individuals with distinct PASC symptoms and sequelae and those with complete
recovery from COVID-19. In Aim 2, we will determine whether specific symptoms and sequelae of PASC are
associated with prolonged evolution of SARS-CoV-2-specific B and T cell responses suggestive of viral antigen
or RNA persistence and facilitated by obesity. In Aim 3, we will use our novel mouse model of SARS-CoV-2 to
evaluate sex differences in the persistence of SARS-CoV-2 RNA or antigen in multiple organs, which may lead
to immune-metabolic dysregulation in tissues and correlate with behavioral signs of PASC in mice. Through
the experiments outlined in this proposal, we will address whether some form of SARS-CoV-2 persistence
contributes to PASC or if PASC is entirely a consequence of a remote virus infection, a question with
enormous clinical implications.

## Key facts

- **NIH application ID:** 10554731
- **Project number:** 3U19AI159822-02S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ANDREA L COX
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,209,546
- **Award type:** 3
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10554731

## Citation

> US National Institutes of Health, RePORTER application 10554731, Sex, obesity, immunometabolism, and viral persistence in post-acute sequelae of SARS-CoV-2 infection (3U19AI159822-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10554731. Licensed CC0.

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