Cross-sectional case-control studies (Blue)
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 cross-sectional study, the authors aimed to determine 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. The authors 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). They 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, 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). The authors concluded that their 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.
Raphael Bernard-Valnet, Sylvain Perriot, Mathieu Canales, Beatrice Pizzarotti, Leonardo Caranzano, Mayté Castro-Jiménez, Jean-Benoit Epiney, Sergiu Vijiala, Paolo Salvioni-Chiabotti, Angelica Anichini, Alexander Salerno, Katia Jaton, Julien Vaucher, Matthieu Perreau, Gilbert Greub, Giuseppe Pantaleo, Renaud A. Du Pasquier. Encephalopathies Associated With Severe COVID-19 Present Neurovascular Unit Alterations Without Evidence for Strong Neuroinflammation. Neurol Neuroimmunol Neuroinflamm Jul 2021, 8 (5) e1029; DOI: 10.1212/NXI.0000000000001029