Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection

A Nuber-Champier; A Cionca; G Breville; P Voruz; I Jacot de Alcântara; G Allali; P H Lalive; L Benzakour; K-O Lövblad; O Braillard; M Nehme; M Coen; J Serratrice; J-L Reny; J Pugin; I Guessous; B N Landis; A Griffa; D Van De Ville; F Assal; J A Péron

doi:10.1016/j.psyneuen.2023.106104

Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection

Psychoneuroendocrinology. 2023 Jul:153:106104. doi: 10.1016/j.psyneuen.2023.106104. Epub 2023 Apr 1.

Authors

A Nuber-Champier¹, A Cionca², G Breville³, P Voruz⁴, I Jacot de Alcântara⁴, G Allali⁵, P H Lalive⁶, L Benzakour⁷, K-O Lövblad⁸, O Braillard⁹, M Nehme⁹, M Coen¹⁰, J Serratrice¹⁰, J-L Reny¹⁰, J Pugin¹¹, I Guessous¹², B N Landis¹³, A Griffa¹⁴, D Van De Ville¹⁵, F Assal⁶, J A Péron¹⁶

Affiliations

¹ Clinical and Experimental Neuropsychology Laboratory, Faculty of Psychology, University of Geneva, Geneva, Switzerland; Neurology Division, Geneva University Hospitals, Switzerland.
² Clinical and Experimental Neuropsychology Laboratory, Faculty of Psychology, University of Geneva, Geneva, Switzerland.
³ Neurology Division, Geneva University Hospitals, Switzerland.
⁴ Clinical and Experimental Neuropsychology Laboratory, Faculty of Psychology, University of Geneva, Geneva, Switzerland; Neurology Division, Geneva University Hospitals, Switzerland; Faculty of Medicine, University of Geneva, Switzerland.
⁵ Leenaards Memory Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁶ Neurology Division, Geneva University Hospitals, Switzerland; Faculty of Medicine, University of Geneva, Switzerland.
⁷ Faculty of Medicine, University of Geneva, Switzerland; Psychiatry Department, Geneva University Hospitals, Switzerland.
⁸ Faculty of Medicine, University of Geneva, Switzerland; Diagnostic and Interventional Neuroradiology Department, Geneva University Hospitals, Switzerland.
⁹ Division and Department of Primary Care Medicine, Geneva University Hospitals, Switzerland.
¹⁰ Division of General Internal Medicine, Department of Medicine, Geneva University Hospitals and Geneva University, Switzerland.
¹¹ Faculty of Medicine, University of Geneva, Switzerland; Intensive Care Department, Geneva University Hospitals, Switzerland.
¹² Faculty of Medicine, University of Geneva, Switzerland; Division and Department of Primary Care Medicine, Geneva University Hospitals, Switzerland.
¹³ Faculty of Medicine, University of Geneva, Switzerland; Rhinology-Olfactology Unit, Otorhinolaryngology Department, Geneva University Hospitals, Switzerland.
¹⁴ Neurology Division, Geneva University Hospitals, Switzerland; Institute of Bioengineering, Center for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Geneva, Switzerland.
¹⁵ Faculty of Medicine, University of Geneva, Switzerland; Institute of Bioengineering, Center for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Geneva, Switzerland.
¹⁶ Clinical and Experimental Neuropsychology Laboratory, Faculty of Psychology, University of Geneva, Geneva, Switzerland; Neurology Division, Geneva University Hospitals, Switzerland. Electronic address: [email protected].

Abstract

Background: A neurocognitive phenotype of post-COVID-19 infection has recently been described that is characterized by a lack of awareness of memory impairment (i.e., anosognosia), altered functional connectivity in the brain's default mode and limbic networks, and an elevated monocyte count. However, the relationship between these cognitive and brain functional connectivity alterations in the chronic phase with the level of cytokines during the acute phase has yet to be identified.

Aim: Determine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6-9 months after infection.

Methods: We analyzed the predictive value of the concentration of acute cytokines (IL-1RA, IL-1β, IL-6, IL-8, IFNγ, G-CSF, GM-CSF) (cytokine panel by multiplex immunoassay) in the plasma of 39 patients (mean age 59 yrs, 38-78) in relation to their anosognosia scores for memory deficits via stepwise linear regression. Then, associations between the different cytokines and brain functional connectivity patterns were analyzed by MRI and multivariate partial least squares correlations for the whole group.

Results: Stepwise regression modeling allowed us to show that acute TNFα levels predicted (R² = 0.145; β = -0.38; p = .017) and were associated (r = -0.587; p < .001) with scores of anosognosia for memory deficits observed 6-9 months post-infection. Finally, high TNFα levels were associated with hippocampal, temporal pole, accumbens nucleus, amygdala, and cerebellum connectivity.

Conclusion: Increased plasma TNFα levels in the acute phase of COVID-19 predict the presence of long-term anosognosia scores and changes in limbic system functional connectivity.

Keywords: Anosognosia; Cognition; Cytokine; Immunology; Post-COVID-19 condition; SARS-CoV-2; TNFα.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Agnosia* / psychology
COVID-19*
Cognitive Dysfunction* / etiology
Cytokines
Humans
Memory Disorders
Tumor Necrosis Factor-alpha

Substances

Cytokines
Tumor Necrosis Factor-alpha
TNF protein, human