Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein, 2023, Lavanya Visvabharathy

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.

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1155770/full

 

Author interviewed on The Long Covid Sessions Podcast, discussing the political factors associated with publishing research into LC. This paper took 2 years to be published and I expect many of its findings have been shown in subsequent papers, so at this point may not be adding much. Discussion starts at 11:00.

The two podcast hosts have an introductory social chat each week about their journey with LC. If listening to this particular episode I would suggest including the intro. It describes the experience of a patient-participant, doing exercise-based physiological research investigations, where - it would seem to me - the investigators have a a dangerously incomplete conceptualisation of the pathology. It sounds as if they were biased to the idea that the problem comes down to simply "an imbalance in the autonomic system" rather than the ANS being a downstream pathological target of immunometabolic disruption/energetic failure/cardiovascular dysfunction etc. "He did tell me that I would feel not very great for the next 36 hours."

The result was encouragement to "keep going" on the exercycle after she'd called "I have to stop". The outcome: something that sounds close to a cardiac arrest scenario. "There was panic stations." She did (finally!) get a diagnosis of POTS though — albeit after 2 years