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

Abstract

BackgroundA 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. AimDetermine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6–9 months after infection. MethodsWe 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. ResultsStepwise 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. ConclusionIncreased 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.