Covid-cog project

Impact neuropsychologique à court et à long terme du COVID-19

Résumé

Depuis son apparition au mois de décembre 2019, le COVID-19 a posé de nombreux défis à notre société. Dans ce cadre, de récentes observations cliniques ont mis en évidence la présence de symptômes neurologiques et neuropsychologiques chez des patient-e-s souffrant d’une infection au COVID-19 au stade aigu mais également à distance de l’infection. Plusieurs hypothèses ont été émises quant aux voies d’infection du système nerveux central.

Le projet COVID-COG, financé par le Fonds National Suisse, vise à i) étudier les possibles séquelles neurologiques et neuropsychologiques à court et long terme au décours de l’infection au COVID-19, ii) déterminer si la présence de ces troubles est corrélée à la gravité de la maladie en phase aiguë, ainsi qu’à iii) étudier les facteurs de vulnérabilité de développer des troubles neuropsychologiques à distance de l’infection.

Dans ce contexte, une batterie de tests neuropsychologiques validés et standardisés évaluant les fonctions cognitives et émotionnelles sera administrée à une large cohorte de patient-e-s à deux temps d’évaluation : 3 à 6 mois puis 9 à 12 mois post infection, en dissociant trois groupes de patient-e-s selon la sévérité de la forme pulmonaire en phase aiguë. En parallèle, une imagerie par résonance magnétique sera réalisée dans le but de corréler les résultats comportementaux à une éventuelle atteinte cérébrale.

Le projet relève de la recherche fondamentale et clinique. La présence d’éventuelles séquelles neuropsychologiques au décours de l’infection au COVID-19 pourrait avoir des conséquences sévères et un coût extrêmement important sur le plan individuel mais également sociétal. Dans ce contexte, le but de ce projet consiste à mieux décrire les conséquences de l’infection au COVID-19 chez l’humain, et fournir les recommandations les plus appropriées quant à la prise en charge clinique à long terme des patient-e-s infecté-e-s par le SARS-COV-2. L’objectif est d’optimiser et d’harmoniser la pratique clinique, ainsi qu’établir une ligne de base pour le développement d’une neuro-rééducation spécifique qui permettrait de minimiser les coûts globaux des conséquences cliniques de l’infection.

Short- and long-term neuropsychological impairment following COVID-19

Abstract

Initially characterized as a severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), new clinical observations in the acute phase of the infection suggest that COVID-19 is also frequently associated with neurological disorders. These observations are supported by recent cohort studies indicating the presence of such disorders in patients with severe COVID-19 infection, in some cases even before the usual respiratory symptoms appear. Mao et al. (2020) found that 36.4% of COVID-19 infected patients had neurological symptoms involving the central nervous system, peripheral nervous system, and skeletal muscles. Encephalopathy is the most common neurological manifestation observed during the acute phase among patients followed in intensive care, but stroke has also been observed. A direct role of the virus is suspected, but cumulative data indicate that an over-exuberant immune response to the virus, which can involve pro-inflammatory cytokines (cytokine storm syndrome), could explain both the acute respiratory disease syndrome and the encephalopathy. At the neuropsychological level, confusion, severe executive dysfunction, and major attention fluctuations are the most commonly reported features (Helms et al., 2020). Although neurological and neuropsychological hypotheses predict their presence, we do not yet know whether there are any short- or long-term neuropsychological sequelae to COVID-19. If there are, another critical question is whether these effects are only present in patients with the most severe forms followed in intensive care, or if they are also present in patients with far milder and even asymptomatic forms. Moreover, are these possible short- and long-term effects correlated with epidemiological risk factors such as age, sex, sociocultural level, body mass index, brain lesions, comorbidities, or the expected neuropsychiatric disease in the wake of this massive public health crisis? These questions are of critical importance regarding the clinical characterization of the virus in humans, and thus fully aligned with the priority areas of the RNP 78 SNSF call (Module 4). In this context, the objective of the COVID-COG project is to assess the possible short- and long-term neuropsychological consequences of COVID-19 at 3-6 months and 12 months after the infection. We will compare patients divided into three groups according to the gravity of the respiratory syndrome during the acute phase of the infection: 1) patients who were followed in intensive care; 2) patients who were hospitalized but did not require intensive care; and 3) patients who tested positive but did not require hospitalization. To this end, we will carry out a comprehensive neuropsychological assessment evaluating cognition, emotion and mood, as well as a brain MRI. Based on observations during the acute phase, we expect to observe executive and attentional disorders among patients without stroke. For patients with stroke, we expect to observe additional deficits, depending on the location of the lesion. The intensity of these deficits may be proportional to the severity of the symptoms during the acute phase, but this question remains totally open. The project will be supervised by Doctor Julie Péron and Professor Frédéric Assal. Dr Péron is Head Neuropsychologist at the Adult Neurology Department of University Hospitals of Geneva (HUG), and Director of the Clinical and Experimental Neuropsychology Laboratory at the Faculty of Psychology and Educational Sciences of Geneva University. Prof. Assal is Head Behavioural Neurologist at HUG’s Adult Neurology Department, and Associate Professor of Neurology at Geneva University’s Faculty of Medicine. The project will also involve six medical doctors involved in the acute-phase care of patients with COVID-19 and will be implemented at HUG, in order to secure a sufficient number of patients, as well as provision of the necessary skills and equipment.