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)

Abstract

IntroductionAlthough 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 methodsWe 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).ResultsAll 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).ConclusionsWe 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.

COVID-19 mRNA vaccination leading to CNS inflammation: a case series

“…In late 2020, the first vaccines for preventing SARS-CoV-2 infection became available with their mechanisms of action based on introducing the inactivated spike protein viral antigen to the host [ 21 , 22 ]. While the COVID-19 vaccines have been shown to be remarkably safe and effective [ 23 ], there are rare reports of presumed post-vaccination neurologic conditions such as Bell’s palsy [ 24 – 26 ], Guillain–Barre syndrome (GBS) [ 22 , 27 , 28 ], transverse myelitis [ 15 , 29 – 32 ], and the first manifestation of MS [ 33 ], or MS relapse [ 34 , 35 ]. Cases of cardiac inflammation have also been reported after COVID-19 vaccination [ 36 – 42 ].…”

SARS-CoV-2 Vaccination-Induced Transverse Myelitis

“…The SARS-CoV-2 structural surface vector glycoprotein antigen (spike protein; nCoV-19) gene is included in a replication-deficient chimpanzee adenoviral ChAdOx1 vaccine (AZD1222). The antigen may also be present in the COVID-19 vaccination AZD1222, or its chimpanzee adenovirus adjuvant could be a possible trigger leading to ATM [ 13 ]. Johnson & Johnson's COVID-19 vaccine incorporates the adenovirus, a prevalent cause of respiratory illnesses.…”

Neuroimmunology and Novel Methods of Treatment for Acute Transverse Myelitis

“…The development of further clinical trials would allow for differentiation and determination of the relationship ATM has with these other conditions. In addition, theories have been proposed to indicate that ATM may have vascular, oncological, bacterial, and viral sources, such as its relation to the COVID-19 pandemic [ 6 ]. Therefore, it is conceivable that multiple mechanisms may be involved in ATM’s presentation, with theories such as molecular mimicry being among the probable theories behind an infectious source [ 10 ].…”

“…Furthermore, 10-30% of patients with ATM go on to develop multiple sclerosis (MS) over a five to ten-year period, making it a presenting feature of MS [ 2 ]. Most recently, there have been multiple case reports associating both coronavirus disease 2019 (COVID-19) infection and COVID-19 vaccination to the development of ATM [ 6 , 7 ]. Other potential propagators of myelitis not mentioned in Table 1 include myelitis associated with the oncological treatment of immune checkpoint inhibitors (ICIs) [ 8 , 9 ].…”