# Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesis

> **NIH NIH P51** · EMORY UNIVERSITY · 2021 · $784,482

## Abstract

Abstract
SARS-CoV-2 continues to spread across the globe at an exponential rate with increasing numbers of patients
in the hospital. Due to the rapid spread, much remains to be understood about viral pathogenesis and host
immune response to infection. Immunological features of COVID-19 progression include a robust pro-
inflammatory response driven by innate and adaptive immune cells. Importantly, very recent studies suggest
that deficiency in type-I interferon (IFN) signaling is associated with life-threatening COVID-19 outcomes in
previously healthy individuals.
Establishment of a non-human primate model of severe SARS-CoV-2 infection could prove essential for
understanding SARS-CoV-2 pathogenesis and for preclinical testing of candidate antiviral agents and immune
modulators able to reduce the extent of viral replication and the excessive inflammation. Herein, we are
proposing extensive and state-of-the-art immunologic analyses in SARS-CoV-2 infected rhesus macaques
(RMs) to identify markers of inflammation and disease severity that can be used to develop a standardized and
robust RM/NHP model of COVID-19 (Aim #1). Furthermore, we will block, specifically and directly in vivo, type-
I IFN responses in SARS-CoV-2-infected RMs (Aim #2) via administration of a type-I IFN antagonist (IFN-I
ant). This intervention will elucidate the roles of type-I IFN in protecting the host from severe COVID-19
progression and investigate if a short-term IFN-I ant treatment can establish a severe and reproducible NHP
COVID-19 model. Additionally, specimens collected longitudinally and at necropsy will be cryo-banked to be
shared and used among the COVTEN consortium for validation of established SOPs as well as for addressing
additional questions related to COVID-19 inflammation and pathogenesis.
The advantage of tracking pathogenesis, immune responses, and viral replication longitudinally, including very
early after infection, and across multiple tissues, including lung, heart, and brain, will allow us to address our
critical questions with a depth and rigor that is virtually impossible to achieve in humans. These achievements
will provide key insights into the mechanisms of SARS-CoV-2 pathogenesis, and will deliver a robust
NHP model for prioritizing and accelerating the development of the most promising candidate
therapeutics. This study will cross-validate COVTEN SOPs and establish a robust model to be utilized by the
ACTIV consortium.

## Key facts

- **NIH application ID:** 10321484
- **Project number:** 3P51OD011132-60S4
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** JONATHAN S LEWIN
- **Activity code:** P51 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $784,482
- **Award type:** 3
- **Project period:** 2020-12-23 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321484

## Citation

> US National Institutes of Health, RePORTER application 10321484, Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesis (3P51OD011132-60S4). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10321484. Licensed CC0.

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