# Project 2: Serologic and molecular determinants of COVID-19 severity and immune protection

> **NIH NIH U54** · OHIO STATE UNIVERSITY · 2022 · $599,757

## Abstract

Project 2 Summary
PROJECT 2. Serologic and molecular determinants of COVID-19 severity and immune protection.
Unresolved scientific questions remain about how the type, kinetics and duration of SARS-CoV-2 serologic
responses correlate with patient age, disease severity, protective immunity, and risk of spread to close
contacts. Our overall goal is to utilize the well-annotated STOP-COVID data sets and longitudinal samples
collected from the first-responder cohort (at high-risk for re-exposure) and family contacts (Project 1, Core B) to
advance understanding of the specific host and viral factors that underlie long-lasting and protective serologic
responses. Our three highly interactive aims include: to identify differences in virus neutralizing (VN) antibody
isotypes and their target viral proteins/peptides/epitopes; to assess cross-protective immunity versus disease
exacerbation by antibodies to common cold CoVs; and to probe, by virus-host transcriptome analysis, how
SARS-CoV titer or sequence and initial immune response at mucosal sites or blood interrelate with disease
outcomes and the above serologic responses. Aim 1: Define immunoglobulin isotypes, titer, target proteins and
viral neutralization activity of SARS-CoV-2 specific Abs and their correlations with disease severity and
protection: We will utilize VN assays (VNA) and a luciferase immunoprecipitation assay to identify VN antibody
isotype specificities and their immunodominant and unique target viral proteins/peptides/epitopes relevant to
disease severity and protection. Expected outcomes include data that delineate the temporal antibody isotypes
and viral targets to refine protocols for serologic testing that align with protective immunity. Aim 2: Determine
the impact of common cold CoVs (CCCoV) and SARS-CoV-2 specific antibodies on COVID-19 protection and
disease severity in a high-exposure risk cohort of first responders and their household contacts. Diagnostic
serum samples will be used in innovative ELISA platforms directed against unique and conserved CCCoV
peptides, and Spike pseudotyped CCCoV to assess CCCoV antibody responses. Expected outcomes include
original data on whether pre-existing CCCoV antibodies relate to COVID-19 clinical symptoms, severity or
strain specificity of SARS-CoV-2 infection (Aim 3), or re-infection risk. Aim 3. Correlate patterns of mucosal and
serologic immune responses with virus and host genetics. We will utilize a novel targeted host-SARS-CoV-2
RNA sequencing assay (CoV-DXVX) to assess whether virus titer or functional alterations in SARS-CoV-2 S1,
S2, N proteins or other ORFs impact disease presentation, progression and outcome. Host response
measured by the profile and strength of mucosal or blood immune gene induction will be correlated with the
duration, type and protective ability of these serologic responses and with the ones above. Once vaccines are
deployed to our first-responder cohort, all 3 aims will pivot to analyze how the above serol...

## Key facts

- **NIH application ID:** 10688394
- **Project number:** 4U54CA260582-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Linda J. Saif
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $599,757
- **Award type:** 4N
- **Project period:** 2020-09-18 → 2025-03-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10688394

## Citation

> US National Institutes of Health, RePORTER application 10688394, Project 2: Serologic and molecular determinants of COVID-19 severity and immune protection (4U54CA260582-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10688394. Licensed CC0.

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