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

J Neurol. 2021 Sep;268(9):3086-3104. doi: 10.1007/s00415-020-10380-x. Epub 2021 Jan 13.


Objective: To systematically describe central (CNS) and peripheral (PNS) nervous system 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 and discharge. Three-month follow-up data were collected using electronic health records. We classified complications as caused by SARS-CoV-2 neurotropism, immune-mediated or critical illness-related.

Results: From April to September 2020, we enrolled 61 consecutively admitted COVID-19 patients, 35 (57%) of whom required intensive care (ICU) management for respiratory failure. Forty-one CNS/PNS complications were identified in 28 of 61 (45.9%) patients and were more frequent in ICU compared to non-ICU patients. The most common CNS complication was encephalopathy (n = 19, 31.1%), which was severe in 13 patients (GCS ≤ 12), including 8 with akinetic mutism. Length of ICU admission was independently associated with encephalopathy (OR = 1.22). 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 para/post-infectious, 34 were secondary to critical illness or other causes, and 4 remained unresolved. Cerebrospinal fluid was negative for SARS-CoV-2 RNA in all 5 patients investigated.

Conclusion: CNS and PNS complications were common in hospitalized COVID-19 patients, particularly in the ICU, and often attributable to critical illness. When COVID-19 was the primary cause for neurological disease, no signs of viral neurotropism were detected, but laboratory changes suggested autoimmune-mediated mechanisms.

Keywords: COVID-19; Coronavirus; Critical illness; Encephalopathy; Myelitis; SARS-COV-2.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • COVID-19*
  • Follow-Up Studies
  • Humans
  • Peripheral Nervous System
  • Prospective Studies
  • RNA, Viral
  • SARS-CoV-2
  • Stroke*


  • RNA, Viral