Understanding cognitive function in post-COVID-19 condition with fatigue: an interdisciplinary multimodal investigation

Abstract

Lingering cognitive symptoms of post-COVID-19 condition (PCC) continue to challenge our understanding, highlighting the need for interdisciplinary research. We investigated whether individuals with PCC and fatigue differ from matched controls across neurocognitive, neuroimaging, and immunological measures, integrating these findings with qualitative phenomenological analyses through multimodal cross-analysis. Individuals with PCC and clinically significant fatigue (n=34), and age-, sex-, and education-matched controls recovered from COVID-19 without PCC (n=37) were included. Assessments encompassed physician evaluation, neuropsychological and functional tests, structural and functional MRI, immunological tests, and qualitative phenomenological analysis of interviews. Data were analyzed using established methods and an interdisciplinary cross-analysis to examine persistent cognitive symptoms in PCC. Group comparisons revealed subtle differences between individuals with PCC and controls, while neurocognitive performance and immunological markers remained within normative ranges. Modest differences in white matter, myelin related, and global brain measures were observed, alongside differences in associations between network connectivity and neurocognitive performance across groups, suggesting reduced network resilience rather than domain specific deficits. This pattern resonated with qualitative phenomenological findings: altered experiences of concentrating and difficulties to execute decisions and actions, despite preserved performance on standard neurocognitive tests. These findings suggest that cognitive symptoms in post-COVID-19 fatigue are associated with subtle neurobiological alterations not captured by standard cognitive assessments. In this highly fatigued sample, converging neuroimaging, neurocognitive and immunological findings point toward reduced network efficiency rather than overt cognitive impairment. Qualitative phenomenological analysis further highlighted altered modes of being in the world characterized by increased cognitive effort and difficulties executing decisions and actions.