Cerebrospinal fluid findings in COVID-19 indicate autoimmunity

Abstract

In The Lancet Microbe's August issue, Grégory Destras and colleagues1Destras G Bal A Escuret V et al.Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic.Lancet Microbe. 2020; 1: e149Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar reported on a retrospective RT-PCR screening of all cerebrospinal fluid (CSF) samples received by the virology laboratory of a single university hospital during the COVID-19 epidemic in France (between Feb 1 and May 11, 2020). Of the CSF samples from the 23 patients with confirmed COVID-19, only two were slightly positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), most likely as a result of contamination by blood. Other studies have reported negative CSF findings in patients with COVID-19, specifically examining samples from patients with confirmed disease and neurological complications, as opposed to the systematic screening operated by Destras and colleagues.1Destras G Bal A Escuret V et al.Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic.Lancet Microbe. 2020; 1: e149Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar Neumann and colleagues2Neumann B Schmidbauer ML Dimitriadis K et al.Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms.J Neurol Sci. 2020; 418117090Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar analysed samples collected from 30 patients in six German centres between March and June, 2020. Bellon and colleagues3Bellon M Schweblin C Lambeng N et al.Cerebrospinal fluid features in SARS-CoV-2 RT-PCR positive patients.Clin Infect Dis. 2020; (published online Aug 8.)https://doi.org/10.1093/cid/ciaa1165Crossref Scopus (16) Google Scholar examined 31 patients. Espíndola and colleagues4Espíndola OM Siqueira M Soares CN et al.Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid.Int J Infect Dis. 2020; 96: 567-569Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar described eight patients and reviewed literature reports on 30 additional cases. All of these studies showed that SARS-CoV-2 is not detectable in the CSF of patients with COVID-19 and neurological manifestations. The importance of these results, and the reason why researchers at different laboratories are focusing on the same line of research, should be found in the question of how the virus can damage the nervous system. Is it a direct or indirect mechanism? The results from the studies mentioned here point toward an indirect mechanism.1Destras G Bal A Escuret V et al.Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic.Lancet Microbe. 2020; 1: e149Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 2Neumann B Schmidbauer ML Dimitriadis K et al.Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms.J Neurol Sci. 2020; 418117090Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar, 3Bellon M Schweblin C Lambeng N et al.Cerebrospinal fluid features in SARS-CoV-2 RT-PCR positive patients.Clin Infect Dis. 2020; (published online Aug 8.)https://doi.org/10.1093/cid/ciaa1165Crossref Scopus (16) Google Scholar, 4Espíndola OM Siqueira M Soares CN et al.Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid.Int J Infect Dis. 2020; 96: 567-569Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar Further results5Franke C Ferse C Kreye J et al.High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms.medRxiv. 2020; (published online July 6.) (preprint)https://doi.org/10.1101/2020.07.01.20143214Google Scholar support an indirect mechanism, showing a high prevalence of autoantibodies, mainly against unknown autoantigens in the brain, in CSF from patients with COVID-19 and neurological complications. It appears, therefore, that neurological manifestations of COVID-19 are not caused by direct cytopathic effects but indirect immune-mediated mechanisms targeting various unknown elements of the nervous system. Testing the immune reactivity of the CSF of patients with COVID-19 and neurological manifestations against candidate targets for autoimmunity might be the next step to elucidate the mechanisms of damage to the nervous system by SARS-CoV-2. I declare no competing interests. Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemicSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged since December, 2019, and spread worldwide, causing the COVID-19 pandemic. Despite COVID-19 being a respiratory tract infection, the pathophysiology in both adults and children is incompletely understood. Neurological signs and symptoms—from headache to meningitis—have been reported in hospitalised patients.1,2 SARS-CoV-2 can enter and replicate in neuronal cells in vitro,3 but the association between neurological manifestations and presence of SARS-CoV-2 in cerebrospinal fluid (CSF) has only been tested in a few cases, with one patient testing positive for SARS-CoV-2 in a case report4 and seven of seven patients testing negative in a case series. Full-Text PDF Open Access