AUTHOR=Visvabharathy Lavanya , Hanson Barbara A. , Orban Zachary S. , Lim Patrick H. , Palacio Nicole M. , Jimenez Millenia , Clark Jeffrey R. , Graham Edith L. , Liotta Eric M. , Tachas George , Penaloza-MacMaster Pablo , Koralnik Igor J. 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1155770

DOI=10.3389/fimmu.2023.1155770

ISSN=1664-3224

ABSTRACT=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 how virus-specific adaptive immunity is affected in these individuals. We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated CD4+ T cell responses toward the C-terminal region of SARS-CoV-2 Nucleocapsid protein when examined both functionally and using TCR sequencing. In contrast, Neuro-PASC patients have diminished activation of CD8+ memory T cells and increased IL-6 production to Nucleocapsid. 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. 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.