Self-reported health, neuropsychological tests and biomarkers in fully recovered COVID-19 patients vs patients with post-COVID cognitive symptoms: a pilot study

Objective Substantial numbers of individuals who contract COVID-19 experience long-lasting cognitive symptoms such as brain fog. Yet research to date has not compared these patients with healthy controls with a history of laboratory-confirmed COVID-19 infection, making it difficult to understand why certain COVID patients develop post-COVID cognitive symptoms while others do not. The objective of this pilot study was to compare two groups of laboratory-confirmed post-COVID patients, with and without cognitive symptoms, on measures of cognitive and psychological functioning, self-reported perceptions of functional status and quality of life, and biomarkers of stress, inflammation, and neuroplasticity. Methods Using a case-control design, 17 participants were recruited from a healthcare system in western Michigan, USA in 2022 through 2024. All participants were aged 25-65 and had a positive polymerase chain reaction (PCR) test confirming previous COVID-19 infection. Ten participants reported cognitive symptoms (long COVID group) while seven were fully recovered with no residual symptoms (controls). All participants underwent an interview on their self-rated health and quality of life, a battery of neurocognitive tests, and blood draw for biomarker analysis. Results No group differences were detected for neuropsychological test measures except for letter fluency where the long COVID group scored significantly lower (p<.05). The long COVID group had significantly lower ratings than controls on quality of life, physical health, emotional functioning, and psychological well-being. Serum levels of nerve growth factor (NGF), a biomarker of brain plasticity, were significantly lower in the long COVID group, which was significantly more likely than controls to have serum levels of inflammatory marker (interleukin (IL)-10) values greater than or equal to the median (p=0.015). Conclusion Biomarker analyses suggest possible prolonged inflammatory processes in long COVID patients compared to fully recovered patients. Results of decreased neuroplastic functioning give credence to patients’ reports of post-COVID changes in brain function.