Dataset Information

Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein.

ABSTRACT:

Introduction

Many people with long COVID symptoms suffer from debilitating neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). Although symptoms of Neuro-PASC are widely documented, it is still unclear whether PASC symptoms impact virus-specific immune responses. Therefore, we examined T cell and antibody responses to SARS-CoV-2 Nucleocapsid protein to identify activation signatures distinguishing Neuro-PASC patients from healthy COVID convalescents.

Results

We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated CD4⁺ T cell responses and diminished CD8⁺ memory T cell activation toward the C-terminal region of SARS-CoV-2 Nucleocapsid protein when examined both functionally and using TCR sequencing. CD8⁺ T cell production of IL-6 correlated with increased plasma IL-6 levels as well as heightened severity of neurologic symptoms, including pain. Elevated plasma immunoregulatory and reduced pro-inflammatory and antiviral response signatures were evident in Neuro-PASC patients compared with COVID convalescent controls without lasting symptoms, correlating with worse neurocognitive dysfunction.

Discussion

We conclude that these data provide new insight into the impact of virus-specific cellular immunity on the pathogenesis of long COVID and pave the way for the rational design of predictive biomarkers and therapeutic interventions.

SUBMITTER: Visvabharathy L

PROVIDER: S-EPMC10258318 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein.

Visvabharathy Lavanya L Hanson Barbara A BA Orban Zachary S ZS Lim Patrick H PH Palacio Nicole M NM Jimenez Millenia M Clark Jeffrey R JR Graham Edith L EL Liotta Eric M EM Tachas George G Penaloza-MacMaster Pablo P Koralnik Igor J IJ

Frontiers in immunology 20230529

<h4>Introduction</h4>Many people with long COVID symptoms suffer from debilitating neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). Although symptoms of Neuro-PASC are widely documented, it is still unclear whether PASC symptoms impact virus-specific immune responses. Therefore, we examined T cell and antibody responses to SARS-CoV-2 Nucleocapsid protein to identify activation signatures distinguishing Neuro-PASC patients from healthy COVID convalescents.<h4>Results</h4>We re ...[more]

PMID: 37313412

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Project description:The Post-acute Sequela of SARS-CoV-2 (PASC) syndrome, also known as Long-COVID, often presents with subjective symptoms such as brain fog and cognitive fatigue. Increased tinnitus, and decreased hearing in noise ability also occur with PASC, yet whether auditory manifestations of PASC are linked with the cognitive symptoms is not known. Electrophysiology, specifically the Auditory Brainstem Response (ABR), provides objective measures of auditory processing. We hypothesized that ABR findings would be linked to PASC and with subjective feelings of cognitive fatigue. Eighty-two individuals, 37 with PASC (mean age: 47.5, Female: 83%) and 45 healthy controls (mean age: 38.5, Female: 76%), were studied with an auditory test battery that included audiometry and ABR measures. Peripheral hearing thresholds did not differ between groups. The PASC group had a higher prevalence of tinnitus, anxiety, depression, and hearing handicap in addition to increased subjective cognitive fatigue. ABR latency findings showed a significantly greater increase in the wave V latency for PASC subjects when a fast (61.1 clicks/sec) compared to a slow click (21.1 clicks/sec) was used. The increase in latency correlated with cognitive fatigue scores and predicted PASC status. The ABR V/I amplitude ratio was examined as a measure of central gain. Although these ratios were not significantly elevated in the full PASC group, to minimize the cofounding effect of age, the cohort was median split on age. Elevated V/I amplitude ratios were significant predictors of both predicted PASC group classification and cognitive fatigue scores in the younger PASC subjects compared to age-matched controls providing evidence of elevated central gain in younger individuals with PASC. More frequent tinnitus also significantly predicted higher subjective cognitive fatigue scores. Our findings suggest that PASC may alter the central auditory pathway and lead to slower conduction and elevated auditory neurophysiology responses at the midbrain, a pattern associated with the typical aging process. This study marks a significant stride toward establishing an objective measure of subjective cognitive fatigue through assessment of the central auditory system.

Dataset Information

Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein.

Introduction

Results

Discussion

Publications

Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein.

Similar Datasets

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