# Role of CASP-11 in SARS-CoV-2-induced lung pathologies and long-term immune protection

> **NIH NIH P01** · OHIO STATE UNIVERSITY · 2024 · $658,785

## Abstract

PROJECT 1 - ABSTRACT
The rapid development of SARS-CoV-2 vaccines has helped ease most of the restrictions in place during the
height of the pandemic to limit transmission of the virus. Unfortunately, the adaptive immunity (i.e., antibody and
T cell responses) induced by current vaccines declines rapidly, thus requiring frequent boosts. Most importantly,
current vaccines fail to optimally protect against emerging SARS-CoV-2 variants of concern (VOCs). The clinical
manifestations of SARS-CoV-2 infections are highly variable, and patients can be asymptomatic or exhibit
symptoms ranging from mild, moderate, or severe conditions that can lead to death. It is estimated that over
30% of SARS-CoV-2 infected people worldwide (~ 65 millions) have developed Post-Acute COVID Syndrome
(PACS), or Long COVID, characterized by pulmonary, mental health, neurological, hematological, diabetes,
gastrointestinal, kidney, musculoskeletal, and cardiovascular disorders. Prior infections do not eliminate risks of
PACS, and 10-12% of cases are after breakthrough SARS-CoV-2 infection in vaccinated individuals
Furthermore, reinfections were recently reported to increase the risks of death, hospitalization and PACS. Thus,
new therapeutic approaches are needed to prevent or better manage acute SARS-CoV-2 infections and PACS.
COVID-19 patients exhibit excessive inflammatory responses and the release of a large amount of pro-
inflammatory cytokines, or cytokine storm which directly correlate with lung injury, multiple organ failure, and an
unfavorable prognosis. We recently observed that human caspase-4 (CASP4), which is a homolog of mouse
CASP11, is significantly upregulated in nasal swabs and lungs of patients with severe SARS-CoV-2 disease.
Furthermore, we found that mice lacking CASP11 develop less severe disease after infection with SARS-CoV-2
and we reported that CASP11 mediates lung pathology, inflammation, and thrombosis during SARS-CoV-2
infection. This project aims to elucidate immune check points regulated by CASP11 during mild, severe COVID-
19 and PACS. We will also test whether targeting CASP11 alone of together with factors which regulate viral
replication during severe SARS-CoV-2 could improve/prevent pathologies and enhance/promote protective
adaptive immunity.

## Key facts

- **NIH application ID:** 10862013
- **Project number:** 1P01AI175399-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Prosper N Boyaka
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $658,785
- **Award type:** 1
- **Project period:** 2024-04-10 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862013

## Citation

> US National Institutes of Health, RePORTER application 10862013, Role of CASP-11 in SARS-CoV-2-induced lung pathologies and long-term immune protection (1P01AI175399-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862013. Licensed CC0.

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