Neuro-COVID long-haulers exhibit broad dysfunction in T cell memory generation and responses to vaccination

Visvabharathy, Lavanya; Hanson, Barbara; Orban, Zachary; Lim, Patrick H.; Palacio, Nicole; Jain, Rishi; Liotta, Eric Michael; Penaloza-MacMaster, Pablo; Koralnik, Igor J.

The high prevalence of post-acute sequelae of SARS-CoV-2 infection (PASC) is a significant health concern. In particular, virus-specific immunity in patients who suffer from chronic neurologic symptoms after mild acute COVID remain poorly understood. Here, we report that neuro-PASC patients have a specific signature composed of humoral and cellular immune responses that are biased towards different structural proteins compared to healthy COVID convalescents. Interestingly, the severity of cognitive deficits or quality of life markers in neuro-PASC patients are associated with reduced effector molecule expressionn in memory T cells. Furthermore, we demonstrate that T cell responses to SARS-CoV-2 mRNA vaccines are aberrantly elevated in longitudinally sampled neuro-PASC patients compared with healthy COVID convalescents. These data provide a framework for the rational design of diagnostics and predictive biomarkers for long-COVID disease, as well as a blueprint for improved therapeutics.