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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.
Subject(s)
Agnosia , COVID-19 , Cognitive Dysfunction , Humans , Agnosia/psychology , Cognitive Dysfunction/etiology , Cytokines , Memory Disorders , Tumor Necrosis Factor-alphaABSTRACT
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.
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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.
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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.
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Cerebral microbleeds (CMB) emerged as a possible complication of COVID-19. We aimed to assess CMB presence, distribution, and potential underlying pathophysiological mechanisms in hospitalised COVID-19 patients. In a cohort of 112 COVID-19 patients with neurological symptoms admitted to the Geneva University Hospital between March 2020 and May 2021, we assessed CMB distribution, and associations with clinical/ radiological variables. Neuroimaging was performed on a 1.5 T MRI with susceptibility-weighted images, 3D time-of-flight angiography, and 3D-contrast-enhanced fat-saturated T1 black blood VISTA sequences. Two neurologists rated CMB using the Microbleed Anatomic Rating Scale and white matter hyperintensities using the Age-Related White Matter Changes score. 53 patients (47.0%) had CMB;in 45.3% of cases, CMB were found in lobar regions with a predilection for temporal (58.3%) and frontal (29.2%) lobes. Deep CMB were present in 18.9%, with corpus callosum CMB found in 15.0%, in 35.9% CMB distribution was mixed. CMB presence was not related to intubation, pulmonary involvement, nor to radiologic signs of endothelitis. Patients with CMB were more likely to have a higher burden of white matter hyperintensities (OR 1.13, p=0.005, 95% CI: 1.03- 1.24), to have hypertension as a comorbidity (OR= 2.34, p= 0.04, 95% CI: 1.04 - 5.30) and to suffer from an acute stroke during hospitalisation (OR: 3.50 p= 0.012, 95% CI:1.31-9.18). In our sample, COVID-19 patients with neurological symptoms had a high burden of CMB. Their distribution suggests that they may be related to cardiovascular risk factors and cerebral amyloid angiopathy. CMB were also associated with an increased risk of acute stroke.
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Background/aims: Many reports have described pain appearance or an increase of chronic pain concomitant to SARS-CoV-2 infection. Here, we describe the cases of three patients with chronic cancer pain, in which COVID-19 was associated with a dramatic reduction/disappearance of pain. Methods: Descriptive report of three oncological patients with chronic pain hospitalized in the contexte of acute COVID-19. Clinical information was personally retrieved by the authors, who also examined the patients. Brain MRI was performed when deemed necessary by the referring physician. Autopsy, when conducted, was performed at the request of family members. All three patients were hospitalized between October 2020 and January 2021 Results: In this case series we describe, for the first time, a group of patients with chronic oncological pain, in which severe SARS-CoV-2 infection resulted in a temporary decrease of pain perception. It should be noted that despite optimal treatment, pain was insufficiently controlled in all cases prior to the infection. Patient 1 suffered from medullary compression at D2 due to probable perivertebral metastasis associated with bone lysis;patient 2 suffered from painful rib metastases;patient 3 suffered from neoplastic infiltration of the rectum from a bladder adenocarcinoma. None of the patients had impaired cognitive function that could have compromised their evaluation of pain. None of the patients complained of dyspnea at the moment of hospitalization;moreover, the reappearance of pain in patient 3 coincided with recovery from COVID-19 and de novo onset of dyspnea. Conclusions: To our knowledge, thisis the first case series reporting an acute reduction in pain perception in COVID-19. We believe further investigation is mandatory, as it could shed new light on the mechanisms of pain perception and modulation.
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Objective: This study aims to compare the clinical characteristics of patients with COVID-19 related encephalopathy with and without radiological signs of intracranial gadolinium vessels enhancement. Background: The SARS-CoV-2 has been associated with neurological complications, including an acute encephalopathy. An unusual intracranial gadolinium vessels enhancement has been reported among these patients;however the prevalence, the clinical characteristics and the association with cerebrovascular complications have not been described yet. Design/Methods: Twenty-nine patients (66.9 ± 9.2 years;10% female) performed an MRI (with 3D T1-weighted black blood VISTA sequences) during acute onset of encephalopathy. The acute encephalopathy was defined by a delirium or a subsyndromal delirium with a pathobiological brain process in patients with a positive SARS-CoV-2 real-time reverse transcription polymerase chain reaction from a nasopharyngeal swab. Results: Twenty-three patients (79%) presented an intracranial gadolinium vessels enhancement, mainly in the vertebral arteries without sign of stenosis. Clinical characteristics were similar between patients with and without intracranial gadolinium enhancement, as well as the prevalence of acute stroke (9% versus 33%, respectively;p-value = 0.119) and microbleeds (52% versus 33%, respectively;p-value = 0.411). Among the 23 patients with an intracranial vessel gadolinium enhancement, 7 patients were treated by high-dose steroid (methylprednisolone 0.5g/d iv for 5 days) with a good clinical outcome. Conclusions: Patients with COVID-19 related encephalopathy present an increased prevalence of intracranial gadolinium vessels enhancement, suggestive of an endotheliitis that is not associated with stroke or microbleeds.
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A significative proportion of patients with pulmonary-related COVID-19 initially present with << silent >> or << happy >> hypoxemia, a term denoting an absence of dyspnea or other respiratory distress symptoms in face of profound hypoxemia. COVID-19 is a multisystemic disease characterized by the diffusion of SARS-COV-2 through the blood and a widespread secondary immune response. Most of the organs are involved, including the brain and this translates into the development of acute encephalopathy and other complications. Silent hypoxemia and the consequent "vanishing dyspnea" represent a loss of warning signal and may be associated with a rapid clinical worsening and a fatal outcome. In this article, we will describe the physiological basis of ventilation and we will elucidate the different pathophysiological mechanisms underlying the phenomenon of silent hypoxemia in COVID-19.