Acute Transverse Myelitis (ATM):Clinical Review of 43 Patients With COVID-19-Associated ATM and 3 Post-Vaccination ATM Serious Adverse Events With the ChAdOx1 nCoV-19 Vaccine (AZD1222)

Front Immunol. 2021 Apr 26;12:653786. doi: 10.3389/fimmu.2021.653786. eCollection 2021.

Abstract

Introduction: Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic.

Case-finding methods: We report a patient from Panama with SARS-CoV-2 infection complicated by ATM and present a comprehensive clinical review of 43 patients with COVID-19-associated ATM from 21 countries published from March 2020 to January 2021. In addition, 3 cases of ATM were reported as serious adverse events during the clinical trials of the COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222).

Results: All patients had typical features of ATM with acute onset of paralysis, sensory level and sphincter deficits due to spinal cord lesions demonstrated by imaging. There were 23 males (53%) and 20 females (47%) ranging from ages 21- to 73- years-old (mean age, 49 years), with two peaks at 29 and 58 years, excluding 3 pediatric cases. The main clinical manifestations were quadriplegia (58%) and paraplegia (42%). MRI reports were available in 40 patients; localized ATM lesions affected ≤3 cord segments (12 cases, 30%) at cervical (5 cases) and thoracic cord levels (7 cases); 28 cases (70%) had longitudinally-extensive ATM (LEATM) involving ≥4 spinal cord segments (cervicothoracic in 18 cases and thoracolumbar-sacral in 10 patients). Acute disseminated encephalomyelitis (ADEM) occurred in 8 patients, mainly women (67%) ranging from 27- to 64-years-old. Three ATM patients also had blindness from myeloneuritis optica (MNO) and two more also had acute motor axonal neuropathy (AMAN).

Conclusions: We found ATM to be an unexpectedly frequent neurological complication of COVID-19. Most cases (68%) had a latency of 10 days to 6 weeks that may indicate post-infectious neurological complications mediated by the host's response to the virus. In 32% a brief latency (15 hours to 5 days) suggested a direct neurotropic effect of SARS-CoV-2. The occurrence of 3 reported ATM adverse effects among 11,636 participants in the AZD1222 vaccine trials is extremely high considering a worldwide incidence of 0.5/million COVID-19-associated ATM cases found in this report. The pathogenesis of ATM remains unknown, but it is conceivable that SARS-CoV-2 antigens -perhaps also present in the AZD1222 COVID-19 vaccine or its chimpanzee adenovirus adjuvant- may induce immune mechanisms leading to the myelitis.

Keywords: COVID-19; COVID-19 ChAdOx1 nCoV-19 vaccine; SARS-CoV-2 neurotropism; myelitis; neurological complications; transverse myelitis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • COVID-19 / complications*
  • COVID-19 Vaccines / adverse effects*
  • ChAdOx1 nCoV-19
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myelitis, Transverse / complications*
  • Myelitis, Transverse / diagnosis
  • Myelitis, Transverse / pathology
  • Myelitis, Transverse / physiopathology
  • Nervous System Diseases / complications
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / pathology
  • Nervous System Diseases / physiopathology
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity*
  • SARS-CoV-2 / physiology
  • Spinal Cord / diagnostic imaging
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Viral Tropism
  • Young Adult

Substances

  • COVID-19 Vaccines
  • ChAdOx1 nCoV-19