Abstract
Persistent symptoms after COVID-19 constitute the long COVID syndrome, also called post-acute sequelae of SARS-CoV-2 infection (PASC). COVID-19 vaccines reduce the gravity of ensuing SARS-CoV-2 infections. However, whether vaccines also have an impact on PASC remain unknown. We investigated whether vaccination prior to infection alters the subsequent neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). We studied prospectively the first consecutive 200 post-hospitalization Neuro-PASC (PNP) and 1100 non-hospitalized Neuro-PASC (NNP) patients evaluated at our neuro-COVID-19 clinic between May 2020 and January 2023. Among PNP patients, 87% had a pre-vaccination infection and 13% had a breakthrough infection post-vaccination. Among the NNP patients, 70.7% had a pre-vaccination infection and 29.3% had a breakthrough infection. Both PNP and NNP breakthrough infection patients had more frequent pre-existing depression/anxiety than their respective pre-vaccination infection groups, and NNP breakthrough infection patients also had more frequent comorbidities of headache, lung and gastrointestinal diseases than the NNP pre-vaccination infection group. An average of 10 months after symptom onset, the three most common neurological symptoms for PNP patients were brain fog (86.5%), numbness/tingling (56.5%) and headache (56.5%). Of all Neuro-PASC symptoms, PNP breakthrough infection more frequently reported anosmia compared to PNP pre-vaccination infection patients (69.2 versus 37.9%; P = 0.005). For NNP patients, the three most common neurological symptoms were brain fog (83.9%), headache (70.9%) and dizziness (53.8%). NNP pre-vaccination infection reported anosmia (56.6 versus 39.1%; P < 0.0001) and dysgeusia (53.3 versus 37.3%; P < 0.0001) more frequently than breakthrough infection patients. NNP breakthrough infection more frequently reported dizziness compared to NNP pre-vaccination infection patients (61.5 versus 50.6%; P = 0.001). Both PNP and NNP patients had impaired quality-of-life in cognitive, fatigue, sleep, anxiety and depression domains with no differences between pre-vaccination infection and breakthrough infection groups. PNP patients performed worse on National Institutes of Health Toolbox tests of processing speed, attention, executive function and working memory than a US normative population whereas NNP patients had lower results in processing, speed, attention and working memory, without differences between pre-vaccination infection and breakthrough infection groups. These results indicate that vaccination prior to SARS-CoV-2 infection does not affect the neurologic manifestations of long COVID in either PNP or NNP patients. Minor differences in neurologic symptoms between pre-vaccination infection and breakthrough infection groups may be caused by SARS-CoV-2 strains evolution. Patients developing Neuro-PASC after breakthrough infection have a higher burden of comorbidities, highlighting different risk factors warranting targeted management.