Neurocognitive trajectories in long COVID: Evidence from longitudinal analyses

Background

Patients frequently report symptoms of cognitive impairment or “brain fog” after acute COVID-19 infection, but the trajectory of these symptoms over time has yet to be determined. We assessed cognitive function over a 42-month period after acute SARS-CoV-2 infection and identified factors associated with the trajectory of cognitive function over this period.

Methods

We analyzed data from participants in the Mount Sinai Health System Post-COVID-19 Registry in New York City, a prospective cohort study of adults followed after acute SARS-CoV-2 infection of any severity. Participants were identified from a list of all patients with COVID-19 who received care at an MSHS facility in New York, recruited beginning April 2020 and followed through January 2024. Cognition was assessed using well-validated in-person measures of attention, working memory, processing speed, executive functioning, language, and memory. We used linear mixed models to investigate the relationships between cognitive scores and time. We also assessed factors (including race, ethnicity, site of acute COVID-19 care, fatigue, depression, anxiety, body mass index, medical comorbidities, and COVID-19 vaccination) that may influence changes in cognitive scores over time.

Findings

We analyzed data from 1553 participants (median age 53 years, 63 % female, 17 % Black, 21 % Hispanic). In adjusted analyses, scores from cognitive measures of attention, working memory, processing speed, executive functions, and verbal learning and memory improved progressively through 42 months post-COVID. However, despite the improvements, on average, measures of processing speed and executive functioning remained ≥1 standard deviation below the normative mean. Having a body mass index of <25 kg/m² was predictive of a greater improvement in cognitive scores.

Interpretation

While cognitive impairment occurring after COVID-19 improved over time in most domains, processing speed and executive functioning remained below the normal range. The cognitive health burden of Long COVID is therefore significant and lasting. Future studies should examine interventions to support rapid recovery, as well as dynamic risk prediction models to determine factors that may impact cognitive recovery longer term.