# COVID 19 Respiratory and CNS Pathogenesis in Geriatric Rhesus Monkeys

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $780,502

## Abstract

Project Summary
Although coronaviruses primarily cause respiratory and intestinal infections, they also have the potential to cause
central nervous system (CNS) complications. There is accumulating evidence of neurological damage in COVID-
19 patients, with neurological symptoms correlating with disease severity. The primary receptor for SARS-CoV-
2, the angiotensin converting enzyme- 2(ACE-2), is expressed by neurons and other cells in the brain providing
a strong rationale to investigate the impact of SARS-CoV-2 infection on the CNS.
The goals of this proposal are to understand CNS viral dissemination and neuroinflammation following
SARS-CoV-2 infection in geriatric rhesus macaques. Because preventing viral entry into the CNS may
be a lifesaving measure in COVID-19 patients, this work is highly urgent. Additionally, susceptibility of
geriatric patients to COVID-19 associated respiratory and CNS complications suggests a role for age-associated
immunosenescence and neurodegeneration in COVID-19 morbidity. Addressing these questions in the
framework of human studies is challenging; therefore, studies in the COVID-19 rhesus model are critically
needed. The goal of this work is to urgently address CNS complications as it relates to age using a COVID-19
rhesus model. Our Aims are:
Aim 1: Characterize SARS-CoV-2 dissemination to CNS and neuroinflammation in young and geriatric rhesus
monkeys.
Aim 2: Determine Efficacy of Convalescent Plasma Therapy in preventing COVID-19 respiratory and CNS
complications in geriatric monkeys.
Urgency and relevance to NOT-AG-20-022: This proposal aligns with the research interests of Division of
Aging Biology and Division of Neuroscience. Our rhesus studies are focused on understanding disease
pathogenesis in older animals and are highly relevant to scope and purpose of this NOSI. Work in animal models
is vital to fully comprehend how SARS-CoV-2 gains access to the CNS and define crucial interventions to resolve
infection without long-term neurocognitive damage.
Feasibility: This urgent competitive revision is within the expertise of the PIs of the original grant and we have
the resources, reagents, and collaborators at the CNPRC to achieve the proposed goals. We have included as
Key Personnel, Dr. Chris Miller and Dr. Koen Von Rompay who are part of the CNPRC team developing COVID-
19 rhesus model. Our strong collaborations with the UC Medical Center clinicians treating COVID-19 patients
gives us a significant advantage in understanding the disease process and identifying and testing interventions
with direct translational relevance. Work in animal models is vital to fully understand how/why SARS-CoV-2 in
more pathogenic in older adults, gains access to the CNS and to define crucial interventions to resolve infection
without long-term pathology. All the lab work will be done in certified (by State, County, and UC system
regulators) BSL3 laboratories at the CIID and the AG BSL3 animal facilities at the CNPRC. The work ...

## Key facts

- **NIH application ID:** 10142115
- **Project number:** 3RF1AG061001-01S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Swaminathan Smita Iyer
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $780,502
- **Award type:** 3
- **Project period:** 2018-09-30 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142115

## Citation

> US National Institutes of Health, RePORTER application 10142115, COVID 19 Respiratory and CNS Pathogenesis in Geriatric Rhesus Monkeys (3RF1AG061001-01S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10142115. Licensed CC0.

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