Observational cohort study of neurological involvement among patients with SARS-CoV-2 infection.

BACKGROUND

A growing number of reports suggest that infection with SARS-CoV-2 often leads to neurological involvement; however, data on the incidence and severity are limited to mainly case reports and retrospective studies.

METHODS

This prospective, cross-sectional study of 102 SARS-CoV-2 PCR positive patients investigated the frequency, type, severity and risk factors as well as underlying pathophysiological mechanisms of neurological involvement (NIV) in COVID-19 patients.

RESULTS

Across the cohort, 59.8% of patients had NIV. Unspecific NIV was suffered by 24.5%, mainly general weakness and cognitive decline or delirium. Mild NIV was found in 9.8%; most commonly, impaired taste or smell. Severe NIV was present in 23.5%; half of these suffered cerebral ischaemia. Incidence of NIV increased with respiratory symptoms of COVID-19. Mortality was higher with increasing NIV severity. Notably, 83.3% with severe NIV had a pre-existing neurological co-morbidity. All cerebrospinal fluid (CSF) samples were negative for SARS-CoV-2 RNA, and SARS-CoV-2 antibody quotient did not suggest intrathecal antibody synthesis. Of the patients with severe NIV, 50% had blood-brain barrier (BBB) disruption and showed a trend of elevated interleukin levels in CSF. Antibodies against neuronal and glial epitopes were detected in 35% of the patients tested.

CONCLUSION

Cerebrovascular events were the most frequent severe NIV and severe NIV was associated with high mortality. Incidence of NIV increased with respiratory symptoms and NIV and pre-existing neurological morbidities were independent risk factors for fatality. Inflammatory involvement due to BBB disruption and cytokine release drives NIV, rather than direct viral invasion. These findings might help physicians define a further patient group requiring particular attention during the pandemic.

Informations de copyright

© The Author(s), 2021.

Déclaration de conflit d'intérêts

Conflict of interest: M. Fleischer reports no disclosures relevant to the manuscript. M. Köhrmann reports no disclosures relevant to the manuscript. S. Dolff reports no disclosures relevant to the manuscript. F. Szepanowski reports no disclosures relevant to the manuscript. K. Schmidt reports no disclosures relevant to the manuscript. F. Herbstreit has received speaker honoraria from Biotest and Maquet Getinge. C. Güngör reports no disclosures relevant to the manuscript. B. Stolte reports no disclosures relevant to the manuscript. Ch. Stadtler reports no disclosures relevant to the manuscript. J. Riße reports no disclosures relevant to the manuscript. O. Witzke has received research grants for clinical studies, speaker’s fees, honoraria and travel expenses from Amgen, Alexion, Astellas, Basilea, Biotest, Bristol-Myers Squibb, Correvio, Chiesi, Gilead, Hexal, Janssen, Dr. F. Köhler Chemie, MSD, Novartis, Roche, Pfizer, Sanofi, TEVA and UCB. M. Fiedler reports no disclosures relevant to the manuscript. A. Mausberg reports no disclosures relevant to the manuscript. C. Kill reports no disclosures relevant to the manuscript. G. Meyer zu Horste has received speaker honoraria and served in advisory boards for LFB Pharma. K. Steiner reports no disclosures relevant to the manuscript. M. Forsting reports no disclosures relevant to the manuscript. U. Sure reports no disclosures relevant to the manuscript. U. Dittmer reports no disclosures relevant to the manuscript. T. Brenner reports no disclosures relevant to the manuscript. C. Kleinschnitz reports no disclosures relevant to the manuscript. M. Stettner served on the scientific advisory and/or received speaker honoraria or travel funding from UCB, Biogen Idec; Grifols, Genzyme, Roche, Merck, Novartis, Octapharma, Sanofi-Aventis, TEVA, and Bayer Healthcare. All authors declare approval of the version that is to be published.