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

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-1ß, 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; ß = -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.

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

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 59, 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 modelling 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 to 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.

Frequency of Abnormally Low Neuropsychological Scores in Post-COVID-19 Syndrome: the Geneva COVID-COG Cohort.

OBJECTIVE: Several studies have reported poor long-term neuropsychological performances in patients following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but none has yet considered the effect of administering multiple intercorrelated neuropsychological tests and assessed the frequency of cognitive deficits in a normative population. Our aim was therefore to assess the presence of cumulative neuropsychological deficits in an actual post-coronavirus disease of 2019 (COVID-19) comparison group versus one simulated using Monte-Carlo methods. METHOD: Validated neuropsychological Monte-Carlo simulation methods were applied to scores from a battery of neuropsychological tests (memory, executive, attentional, perceptual, logical reasoning, language, and ideomotor praxis) administered to 121 patients who had had mild, moderate, or severe COVID-19 (mean age: 56.70 years; 32% women), 222 ± 43 days post-infection. The cumulative percentages of the three severity subgroups were compared with the results of a false discovery rate-corrected probability analysis based on normative data. RESULTS: The cumulative percentages of deficits in memory and executive functions among the severe and moderate patients were significantly higher than those estimated for the normative population. Moderate patients also had significantly more deficits in perception and logical reasoning. In contrast, the mild group did not have significantly more cumulative deficits. CONCLUSIONS: Moderate and severe forms of COVID-19 cause greater long-term neuropsychological deficits than those that would be found in a normative population, reinforcing the hypothesis of long-term effects of SARS-CoV-2 on cognitive function, independent of the severity of the initial infection.

Monocytosis in the acute phase of SARS-CoV-2 infection predicts the presence of anosognosia for cognitive deficits in the chronic phase.

Reduced awareness of neuropsychological disorders (i.e., anosognosia) is a striking symptom of post-COVID-19 condition. Some leukocyte markers in the acute phase may predict the presence of anosognosia in the chronic phase, but they have not yet been identified. This study aimed to determine whether patients with anosognosia for their memory deficits in the chronic phase presented specific leukocyte distribution in the acute phase, and if so, whether these leukocyte levels might be predictive of anosognosia. First, we compared the acute immunological data (i.e., white blood cell differentiation count) of 20 patients who displayed anosognosia 6-9 months after being infected with SARS-CoV-2 (230.25 ± 46.65 days) versus 41 patients infected with SARS-Cov-2 who did not develop anosognosia. Second, we performed an ROC analysis to evaluate the predictive value of the leukocyte markers that emerged from this comparison. Blood circulating monocytes (%) in the acute phase of SARS-CoV-2 infection were associated with long-term post-COVID-19 anosognosia. A monocyte percentage of 7.35% of the total number of leukocytes at admission seemed to predict the presence of chronic anosognosia 6-9 months after infection.