From 'mental fog' to post-acute COVID-19 syndrome's executive function alteration: Implications for clinical approach

Stefano Pallanti; Michele Di Ponzio; Gioele Gavazzi; Gregory Gasic; Bianca Besteher; Carina Heller; Ron Kikinis; Nikos Makris; Zora Kikinis

doi:10.1016/j.jpsychires.2023.09.017

From 'mental fog' to post-acute COVID-19 syndrome's executive function alteration: Implications for clinical approach

J Psychiatr Res. 2023 Sep 30:167:10-15. doi: 10.1016/j.jpsychires.2023.09.017. Online ahead of print.

Authors

Stefano Pallanti¹, Michele Di Ponzio², Gioele Gavazzi³, Gregory Gasic², Bianca Besteher⁴, Carina Heller⁵, Ron Kikinis⁶, Nikos Makris⁷, Zora Kikinis⁸

Affiliations

¹ Department of Psychiatry and Behavioural Science, Albert Einstein College of Medicine, Bronx, USA; Istituto di Neuroscienze, Florence, Italy. Electronic address: stefanopallanti@yahoo.it.
² Istituto di Neuroscienze, Florence, Italy.
³ Department of Neuroscience, Psychology, Drug Research, Child Health, University of Florence, Florence, Italy.
⁴ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
⁵ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Department of Clinical Psychology, Friedrich-Schiller-University Jena, Jena, Germany; Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Morphometric Analysis, Departments of Psychiatry, Neurology and A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Boston, MA, USA; Department of Anatomy and Neurobiology, Boston University Medical School, Boston, USA.
⁸ Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

PMID: 37804756
DOI: 10.1016/j.jpsychires.2023.09.017

Abstract

A common symptom of the neuropsychiatric Post-Acute COVID-19 syndrome (neuro-PACS) is the so called 'brain fog'. Patients describe the brain fog as problems with attention, memory and mental fatigue. Brain fog is experienced by 9-55% of people for months after having contracted SARS-CoV-2 virus. Several theories have been proposed to explain PACS's brain fog, including a neuroinflammatory hypothesis, but the hypothesis remains to be proven. Here, we examined inflammatory and immunological blood profile in a cohort of patients with PACS to investigate the association between executive functions and blood inflammatory markers. Executive function was assessed by the Trail Making Test (TMT) Part A and Part B, as well as the Barkley Deficits in Executive Functioning Scale (BDEFS), in 71 patients (36 men), average age of 40 years (range: 15-82, SD: 15.7). Impairment in executive functioning (BDEFS scores and TMT B scores) correlated with increased levels of Interleukin-6 (IL-6), fibrinogen and ferritin. Moreover, elevated levels of Il-6, fibrinogen, ferritin, tumor necrosis factor-alpha and C-reactive protein have been observed in PACS. These findings demonstrate that PACS is characterized by the presence of an immuno-inflammatory process, which is associated with diminished executive functioning. Here, we argue in favour of a shift from the non-descriptive definition of 'mental fog' to a characterization of a subtype of PACS, associated with alteration in executive functioning. Implication for clinical settings and prevention are discussed.

Keywords: Brain frog; COVID-19; Executive functions; Fibrinogen; Immune response; Inflammation; Interleukin-6; Long-COVID; Post-acute COVID-19 syndrome.