Central and peripheral nervous system complications of COVID-19: A prospective tertiary center cohort with 3-month follow-up

Nersesjan, V.; Amiri, M.; Lebech, A.-M.; Roed, C.; Mens, H.; Russell, L.; Fonsmark, L.; Berntsen, M.; Sigurdsson, S. T.; Carlsen, J.; Langkilde, A.; Martens, P.; Lund, E. L.; Hansen, K.; Jespersen, B.; Folke, M. N.; Meden, P.; Hejl, A.-M.; Warmberg, C.; Benros, M.; Kondziella, D.

Objective: To systematically describe CNS and PNS complications in hospitalized COVID-19 patients. Methods: We conducted a prospective, consecutive, observational study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatric symptoms during admission, at discharge and at 3-month follow-up. We classified complications as caused by SARS-CoV-2 neurotropism, immune-mediated or critical illness-related. Results: From April-September 2020, we enrolled 61 consecutively admitted COVID-19 patients, 35 (57%) of whom were referred to ICU for respiratory failure. Evaluation revealed a higher frequency of CNS/PNS symptoms in ICU patients compared to non-ICU patients. The most common CNS complication was encephalopathy (n=22, 36.1%), which was severe in 13 patients (GCS[≤]12), including 8 with akinetic mutism. Length of ICU admission was an independent predictor of encephalopathy (OR=1.23). Other CNS complications included ischemic stroke, a biopsy-proven acute necrotizing encephalitis, and transverse myelitis. The most common PNS complication was critical illness polyneuromyopathy (13.1%), with prolonged ICU stay as independent predictor (OR=1.14). Treatment-related PNS complications included meralgia paresthetica. Of 41 complications in total, 3 were classified as para/post-infectious. The remainder included cases secondary to critical illness or other causes (n=34) or without sufficient investigations (n=4). Cerebrospinal fluid was negative for SARS-CoV-2 RNA in all 5 patients investigated. Conclusions: CNS/PNS complications were common in hospitalized COVID-19 patients, particularly in ICU patients, and often attributable to critical illness. In cases with COVID-19 as the primary cause for neurological disease, there were no signs of viral neurotropism, but laboratory changes suggested autoimmune-mediated mechanisms.