ABSTRACT
Post-COVID prevalence's is estimated at 10 % in the general population. The neuropsychiatric symptoms, which are frequent (up to 30 %), can severely affect the quality of life of patients affected by this condition, notably by significantly reducing their working ability. To date, no pharmacologic treatment is available for post-COVID, apart from symptomatic treatments. A large number of pharmacological clinical trials for post-COVID are underway since 2021. A number of these trials targets neuropsychiatric symptoms, based on the various underlying pathophysiological hypotheses. The objective of this narrative review is to provide an overview of these ongoing trials targeting neuropsychiatric symptoms in post-COVID.
La prévalence du syndrome post-Covid est évaluée à 10 % dans la population générale. Les symptômes neuropsychiatriques, fréquents (jusqu'à 30 %), peuvent sévèrement affecter la qualité de vie des patients qui en sont atteints et, notamment, en réduisant significativement leur capacité de travail. À ce jour, il n'existe pas de traitement médicamenteux pour le syndrome post-Covid, en dehors des traitements symptomatiques. C'est pourquoi, un grand nombre d'essais thérapeutiques concernant le post-Covid sont en cours depuis 2021. Un certain nombre d'entre eux ciblent les symptômes neuropsychiatriques en se basant sur les diverses hypothèses physiopathologiques élaborées sur le post-Covid. L'objectif de cette revue narrative est d'établir un état des lieux des essais thérapeutiques en cours ciblant les symptômes neuropsychiatriques du post-Covid.
Subject(s)
COVID-19 , Mental Disorders , Humans , Quality of Life , Mental Disorders/drug therapy , Mental Disorders/etiologyABSTRACT
OBJECTIVE: Coronavirus disease (COVID-19) has been associated with a large variety of neurologic disorders. However, the mechanisms underlying these neurologic complications remain elusive. In this study, we aimed at determining whether neurologic symptoms were caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) direct infection or by either systemic or local proinflammatory mediators. METHODS: In this cross-sectional study, we checked for SARS-CoV-2 RNA by quantitative reverse transcription PCR, SARS-CoV-2-specific antibodies, and 49 cytokines/chemokines/growth factors (by Luminex) in the CSF +/- sera of a cohort of 22 COVID-19 patients with neurologic presentation and 55 neurologic control patients (inflammatory neurologic disorder [IND], noninflammatory neurologic disorder, and MS). RESULTS: We detected anti-SARS-CoV-2 immunoglobulin G in patients with severe COVID-19 with signs of intrathecal synthesis for some of them. Of the 4 categories of tested patients, the CSF of IND exhibited the highest level of cytokines, chemokines, and growth factors. By contrast, patients with COVID-19 did not present overall upregulation of inflammatory mediators in the CSF. However, patients with severe COVID-19 (intensive care unit patients) exhibited higher concentrations of CCL2, CXCL8, and vascular endothelium growth factor A (VEGF-A) in the CSF than patients with a milder form of COVID-19. In addition, we could show that intrathecal CXCL8 synthesis was linked to an elevated albumin ratio and correlated with the increase of peripheral inflammation (serum hepatocyte growth factor [HGF] and CXCL10). CONCLUSIONS: Our results do not indicate active replication of SARS-CoV-2 in the CSF or signs of massive inflammation in the CSF compartment but highlight a specific impairment of the neurovascular unit linked to intrathecal production of CXCL8.