# Humoral Immune Mechanisms of Acute and Chronic Neurologic Sequelae of COVID-19

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $629,459

## Abstract

PROJECT SUMMARY
 COVID-19 is associated with a growing number of peripheral and central nervous system complications.
It has become clear that a subset of these syndromes, including acute necrotizing encephalopathy, steroid-
responsive encephalitis and Guillain-Barré syndrome, are likely due to direct viral neuroinvasion and/or
autoimmunity triggered by SARS-CoV-2. There is an urgent need to prospectively investigate the acute and
chronic neurologic complications of COVID-19 and determine which syndromes are neuroinflammatory in origin.
While anti-viral therapeutics are still being developed for SARS-CoV-2, autoimmune CNS conditions can be very
responsive to immunosuppression. Thus, identifying biomarkers for a subset of COVID-19 patients with
autoimmune CNS syndromes in particular could immediately impact clinical management.
 Over the past 8 years, a unique interdisciplinary team of neurologists and basic scientists at UCSF was
formed to develop and deploy an integrated approach to rapidly identify microbial nucleic acid, anti-viral
antibodies and anti-neural antibodies associated with encephalitis, with the explicit intent to discover and
validate clinically actionable biomarkers in addition to uncovering the fundamental mechanisms of disease
pathogenesis underlying these syndromes. The centerpiece of these efforts is an ongoing patient cohort called
the NID (Neuroinflammatory Disease) cohort, consisting of patients with suspected infectious or inflammatory
encephalitis. This cohort is now >1,400 patients referred by clinicians at UCSF and from other centers around
the world. Already, this cohort has spurred the development of the first ever clinically validated cerebrospinal
fluid metagenomic next-generation sequencing assay, the identification of a novel paraneoplastic autoimmune
syndrome with important implications for men with seminoma and the identification of enteroviral CSF
antibodies in children with acute flaccid myelitis. Here, we propose to adapt this existing clinical research
and laboratory infrastructure to enroll and investigate the urgent question whether COVID-19 patients
with ongoing neurologic sequelae have CNS inflammation. We will perform this work in collaboration
with colleagues at the NIH, Yale University as well as at UCSF Medical Center, Zuckerberg San
Francisco General Hospital and UCSF Benioff Children’s Hospital. Using our unique clinical and molecular
approach, we will investigate this hypothesis through the following specific aims:
Aim 1: Characterize autoantibodies in the CSF of COVID-19 patients with acute and chronic neurologic
syndromes
Aim 2: Identify CSF specific antibody repertoires in COVID-19 patients with neurologic complications using
high-resolution SARS-CoV-2 proteome-wide antibody profiling
Aim 3: Elucidate autoantibody pathogenicity through production of monoclonal antibodies from clonally
expanded CSF B cells in COVID-19 patients to enable the development of animal models of disease

## Key facts

- **NIH application ID:** 10573297
- **Project number:** 5R01NS125693-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** SAMUEL JEREMY PLEASURE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $629,459
- **Award type:** 5
- **Project period:** 2022-02-15 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10573297

## Citation

> US National Institutes of Health, RePORTER application 10573297, Humoral Immune Mechanisms of Acute and Chronic Neurologic Sequelae of COVID-19 (5R01NS125693-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10573297. Licensed CC0.

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