Characterizing long-COVID brain fog: a retrospective cohort study

Background Long COVID or post-COVID condition (PCC) is a common complication following acute COVID-19 infection. PCC is a multi-systems disease with neurocognitive impairment frequently reported regardless of age. Little is known about the risk factors, associated biomarkers and clinical trajectory of patients with this symptom. Objective To determine differences in clinical risk factors, associated biochemical markers and longitudinal clinical trajectories between patients with PCC with subjective neurocognitive symptoms (NC+) or without (NC−). Methods A retrospective longitudinal cohort study was performed using a well-characterized provincial database of patients with clinically confirmed PCC separated into NC+ and NC− cohorts. Demographical, clinical and biochemical differences at initial consultation between the two patient cohorts were analyzed in cross-section. Multivariate regression analyses were conducted to identify independent risk factors for neurocognitive impairment. Determination of the recovery trajectory was performed using serial assessments of the patient-reported health-related quality of life (HR-QoL) metric Eq-5D-5L-vas score. Findings Women, milder acute infection and pre-existing mental health diagnoses were independently associated with subjective neurocognitive impairment at 8 months post-infection. NC + patients demonstrated lower levels of IgG, IgG1 and IgG3 compared to NC− patients. The NC + cohort had poorer HR-QoL at initial consultation 8 months post-infection with gradual improvement over 20 months post-infection. Conclusions Neurocognitive impairment represents a severe phenotype of PCC, associated with unique risk factors, aberrancy in immune response and a delayed recovery trajectory. Those with risk factors for neurocognitive impairment can be identified early in the disease trajectory for more intense medical follow-up.