# COVID-19: Characterizing trained immune responses to COVID-19

> **NIH VA I01** · JAMES H QUILLEN VA MEDICAL CENTER · 2021 · —

## Abstract

In late 2019, a novel human betacoronavirus emerged in Wuhan, China and subsequently led to
pandemic spread. Designated Severe Acute Respiratory Virus 2 (SARS CoV-2), this virus has spawned a
coronaviral infection (COVID-19) that has threatened world populations and overwhelmed healthcare
systems globally. Host immune responses during COVID-19 clearly play a significant role in viral
clearance as well as pulmonary progression, but these responses are yet to be characterized. Most
notably, the innate immune responses required for viral clearance and resistance to repeated infections are
not yet known. Recent studies also suggest that these innate immune responses can also form
immunologic memory (“trained immunity”) that occurs independently of B and T cells and results from
epigenetic reprogramming of monocytes, macrophage and NK cell functions that alters their intracellular
signaling and cellular metabolism patterns. This reprogramming allows them to acquire enhanced
capability to respond to secondary stimulation by related or unrelated infectious agents. Because data from
related coronaviruses suggest that innate immune responses are fundamentally important to pathogenesis,
we hypothesize that NK/monocyte responses to viral proteins are necessary to maximize host immune
responses. In this proposal, we will comprehensively investigate the importance of innate immune cells in
the development of anamnestic adaptive responses to SARS CoV-2 antigen, and the role of NK and
monocytes/macrophages in trained innate immune responses to viral antigen, from a clinically
characterized cohort of COVID-19 patients following recovery. In aim 1, we will determine the importance
of innate immune responses in responding to repeat exposure to viral antigens following COVID-19
recovery by 1) assessing the necessity of innate immune cells in generating anamnestic adaptive cellular
responses to SARS CoV-2, and 2) characterizing the cross-reactivity of betacoronaviral antigens in
inducing NK/monocyte responses including phenotypic changes, activation, proliferation, and cytokine
expression, in COVID-recovered subjects. In aim 2, we identify innate trained immune responses to SARS
CoV-2 antigens following COVID-19 recovery by examining if either NK cells or monocytes/macrophages
from COVID-19 recovered subjects exhibit innate immune memory to SARS CoV-2 as assayed by
functional, metabolic, and epigenetic changes These novel translational studies will produce key, relevant
data on host immunity to COVID-19 infection, informing vaccine design and enhancing our understanding
of innate immune memory and the correlates of protective immunity.

## Key facts

- **NIH application ID:** 10148949
- **Project number:** 1I01BX005428-01
- **Recipient organization:** JAMES H QUILLEN VA MEDICAL CENTER
- **Principal Investigator:** JONATHAN P MOORMAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148949

## Citation

> US National Institutes of Health, RePORTER application 10148949, COVID-19: Characterizing trained immune responses to COVID-19 (1I01BX005428-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10148949. Licensed CC0.

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