# Developing an NHP model for understanding the biological causes of long COVID-19 pathogenesis

> **NIH NIH P51** · EMORY UNIVERSITY · 2021 · $499,999

## Abstract

Abstract
As of April 30, 2021, the COVID-19 pandemic has resulted in more that 148 million cases and with 3.1 million
deaths worldwide. Typically, people recover from COVID-19 after 2 to 6 weeks; however, in a significant fraction
of patients symptoms may linger or recur for weeks or months following initial recovery. These “long COVID-19”
symptoms or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) include fatigue or muscle weakness, sleep
disorders, loss of taste or smell, confusion, anxiety, and depression. While the clinical characteristics and
pathogenesis of acute COVID-19 disease are being intensively studied, the long-term consequences of disease
remain largely unknown. Furthermore, the small number of PASC research studies published to date are limited
by a relatively short follow-up after patients are discharged from the hospital; a lack of pre-infection data; and
limited sampling of tissues. Here, taking advantage of a recently established nonhuman primate (NHP) model of
SARS-CoV-2 infection, we aim to establish biosafety guidelines to validate and standardize PASC NHP
studies in rhesus macaques- up to 18 weeks post-infection – in which animals repeatedly testing negative for
SARS-CoV-2 will be transferred from ABSL-3 to ABSL-2+ facilities (Aim 1). This ability to transfer animals from
ABSL-3 facilities will be critical to allow the study of PASC in NHP with acceptable costs and labor, while
preserving the safety of personnel and the NHP colonies. Transfer of animals to BSL-2+ will allow us to
characterize neurological and behavioral manifestations observed in human PASC. Additionally, we are
proposing extensive and state-of-the-art immunologic and virologic analyses in a long-term study of SARS-CoV-
2-infected rhesus macaques (RMs) to define the pathogenesis and identify mechanisms underlying PASC
(Aim 2). Importantly, our study will contribute to the establishment of NHP models of SARS-CoV-2 infection and
could prove essential for understanding long-term effects of SARS-CoV-2 pathogenesis. This model provides
longitudinal assessment of disease findings, pathogenesis, immune responses, and viral persistence.
Furthermore, collection of multiple tissues virtually impossible to obtain in humans, such as gut, brain, heart and
lung, will allow us to identify pulmonary and extra-pulmonary long-term and/or permanent damage. Finally,
specimens collected longitudinally and at necropsy will be cryo-banked and will be key in bridging our discoveries
with data compiled in SARS-CoV-2 recovery human cohorts. These studies will allow us to dissect biological
causes underlying PASC, thus providing key insights for preventing and treating the effects of long-term COVID-
19 disease. The proposed studies are within the scope of the parent award and are highly likely to foster
additional research funding leading to the progress of the overall goals of the parent award. However, there is
no overlap with work already funded in the parent award.

## Key facts

- **NIH application ID:** 10404760
- **Project number:** 3P51OD011132-61S2
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** JONATHAN S LEWIN
- **Activity code:** P51 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $499,999
- **Award type:** 3
- **Project period:** 2021-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404760

## Citation

> US National Institutes of Health, RePORTER application 10404760, Developing an NHP model for understanding the biological causes of long COVID-19 pathogenesis (3P51OD011132-61S2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10404760. Licensed CC0.

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