Multiparametric analysis reveal no intrathecal inflammation in COVID-19 associated neurological syndromes

ABSTRACT

Background and aims: Coronavirus disease (COVID-19) has been associated with a large variety of neurological disorders. However the mechanisms underlying these neurological complications remain elusive. In this study we aimed at determining whether neurological symptoms were caused by SARS-CoV-2 direct infection of by proinflammatory mediators. Methods: We checked for SARS-CoV-2 RNA by RT-qPCR, SARS-CoV-2-specific antibodies and for 48 cytokines/ chemokines/growth factors (by Luminex) in the cerebrospinal fluids (CSF) ± sera of a cohort of 17 COVID- 19 patients with neurological presentation and 55 neurological control patients (inflammatory [IND], non inflammatory [NIND], multiple sclerosis [MS]). Results: We found SARS-CoV-2 RNA and antibodies specific for this virus in the CSF of 0/17 and 8/16 COVID- 19 patients, respectively. The presence of SARS-CoV-2 antibodies was explained by a rupture of the blood brain barrier (passive transfer) in 6/16 (38%). An intrathecal synthesis of SARS-CoV2-specific antibodies was present in 2/16 patients. Of the four categories of tested patients, the CSF of IND exhibited the highest level of chemokines (CCL4, CCL5, CXCL8, CXCL10, CXCL12, and CXCL13), followed by the CSF of MS patients (CXCL12, and CXCL13). There was no significant difference between COVID-19 and NIND patients, even if some chemokines (CCL4, CCL5, CXCL8, andCXCL10) tended to be higher in the former. Interestingly, among COVD-19 patients, the CSF of those with a severe disease (encephalitis/ encephalopathy) contained higher levels CXCL8 and CXCL10 than those with other neurological presentations. Conclusion: Our results do not show obvious SARS-CoV-2 infection of the central nervous system, but point to a mild inflammatory reaction reflecting an astrocytic reaction.