# Dissecting the drivers of persistent SARS-CoV-2 infections

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $844,998

## Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by the betacoronavirus “severe acute respiratory
syndrome coronavirus 2” (SARS-CoV-2) represents an unprecedented public health emergency. Most patients
with COVID-19 clear the virus upon resolution of the acute infection but ongoing, persistent, SARS-CoV-2
replication has been documented in immunocompromised individuals. In these chronically infected patients,
recovery of replication-competent virus over several weeks to months is linked to stepwise acquisition of
mutations within and outside of spike. Our preliminary data show that such prolonged intra-host viral evolution
plays a role in the emergence of new, antigenically distinct, SARS-CoV-2 variants. We propose to systematically
elucidate the determinants of persistent SARS-CoV-2 infections using an integrated translational research
approach combining real-world clinical metadata with bioinformatics, genomics and molecular virology. We will
leverage an existing large surveillance dataset covering two and a half years of SARS-CoV-2 spread in New
York City going back to the beginning of the pandemic in the spring of 2020 when the NY metropolitan area
emerged as one of the early epicenters of the pandemic. Specific Aim 1 will dissect the clinical features and
therapeutic interventions associated with persistent SARS-CoV-2 replication using existing longitudinal data from
electronic medical records. These studies will be complemented by the analysis of the B and T cell populations
of persistently infected patients. Specific Aim 2 will dissect the viral genotypes representative of intra-host
evolution of prolonged periods with a special emphasis on co-circulating viral variants. Specific Aim 3 will
examine the phenotypic properties of persistent SARS-CoV-2 variants with an emphasis on convergent evolution
within and outside of the spike region (susceptibility to neutralization, fusogenicity, spike processing and
interferon antagonism).
Altogether, the proposed studies address a critical knowledge gap regarding the biological drivers and viral
dynamics fueling the selection of SARS-CoV-2 viral variants during persistent SARS-CoV-2 infection. This
knowledge will provide the scientific basis needed to treat and prevent such chronic infections thereby limiting
the emergence and spread of increasingly neutralization-resistant yet transmissible SARS-CoV-2 variants.

## Key facts

- **NIH application ID:** 10889260
- **Project number:** 5R01AI171569-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Viviana A Simon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $844,998
- **Award type:** 5
- **Project period:** 2023-07-17 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889260

## Citation

> US National Institutes of Health, RePORTER application 10889260, Dissecting the drivers of persistent SARS-CoV-2 infections (5R01AI171569-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10889260. Licensed CC0.

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