With input from Dr Monica Vasudev

1. AstraZeneca had voluntarily halted a randomized clinical trial of its coronavirus vaccine after a volunteer developed transverse myelitis (NY Times).
2. Phase 1/2, single-blind, randomized controlled trial at five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control.
3. We presume that the team has confirmed that the case was not in the control arm.
4. ChAdOx1 nCoV-19 given at a dose of 5 × 10¹⁰ viral particles
5. The booster vaccine administered 28 days after the first dose.
6. ChAdOx1 nCoV-19 is made from a virus (ChAdOx1), which is a weakened form of a common cold virus (adenovirus) known to cause infections in chimpanzees; it has been genetically changed thus rendering it impossible to grow in humans.  Genetic material has been added to the ChAdOx1 construct that is used to make proteins from the COVID-19 virus (SARS-CoV-2) called Spike glycoprotein (S). This protein is usually found on the surface of SARS-CoV-2 and plays a pivotal role in the infection pathway of the SARS-CoV-2 virus. The SARS-CoV-2 virus uses its spike protein to bind to ACE2 receptors on human cells and enters the cells and causes an infection. [https://www.ox.ac.uk/news/2020-05-22-oxford-covid-19-vaccine-begin-phase-iiiii-human-trials]
7. The patented Vaccitech adenovirus vectors are chimpanzee adenovirus Oxford 1 and 2 (ChAdOx1 and ChAdOx2), and belong to the group E simian adenovirus family, similar to the chimpanzee adenovirus 63. These viruses have been engineered to make them replication deficient and can be manufactured in well-established HEK293 cell lines containing the adenoviral E1 gene. The viruses have high carrying capacity for the genes encoding cancer or pathogen antigens of interest. [https://www.vaccitech.co.uk/technology/
8. Chimps can have transverse myelitis

[Tetraparesis resembling acute transverse myelitis in a captive chimpanzee (Pan troglodytes): long‐term care and recovery. Journal of Medical Primatology 39(5):336 – 346]

9. Adenoviruses and transverse myelitis: Species B adenoviruses can be linked with more severe disease, including severe pneumonia, aseptic meningitis, encephalitis, and transverse myelitis. Amongst species B adenovirus, type 21 (Ad21) may have caused paralysis. [Clinical Infectious Diseases, Volume 36, Issue 5, 1 March 2003, Pages 550–559]
10. Acute transverse myelitis is seen in COVID-19 infection 

[https://casereports.bmj.com/content/13/8/e236720]

Investigators did not detect SARS-CoV-2 RNA in the CSF and postulated that this presentation was likely a result of an immune-mediated inflammatory process rather than direct invasion of SARS-CoV-2 into the CNS.

The incidence of acute myelitis associated with COVID-19 infection is not clearly understood. Three case reports of similar cases have been noted to link COVID-19 to acute myelitis as a neurological complication. The first one is in Wuhan, China by Kang Zhao et al where COVID-19 was first reported. The second is in Boston where the patient presented with symptoms of upper respiratory tract infection and then developed acute myelitis 7 days later by Sarma et al. Whether the myelitis occurs directly from the viral infection or as an autoimmune sequalae is still not known.  [https://www.sciencedirect.com/science/article/pii/S1930043320302478]

Acute transverse myelitis (TM)

It is a neuro-inflammatory spinal cord disorder presenting with rapid onset of weakness, sensory alterations, and/or bowel and bladder dysfunction.

Types: Idiopathic TM occurs without a definite etiology. Secondary (disease-associated) TM is related to a systemic inflammatory autoimmune condition. Idiopathic TM is often a postinfectious complication and presumably results from an autoimmune process.

TM can be associated with infectious, systemic inflammatory, or multifocal central nervous system disease. Acquired central nervous system demyelinating disorders known to cause TM include multiple sclerosis, neuromyelitis optica, and acute disseminated encephalomyelitis.

Incidence: 1-8 new cases per million.

Onset: acute or subacute development of neurologic signs and symptoms consisting of motor, sensory, and/or autonomic dysfunction. Motor symptoms include rapidly progressing paraparesis that may involve the upper extremities; initial flaccidity followed by spasticity. In most patients, a sensory level can be identified. Sensory symptoms include pain, dysesthesia and paresthesia. Autonomic symptoms involve heightened urinary urgency, bladder and bowel incontinence, difficulty or inability to void, incomplete evacuation and bowel constipation, and sexual dysfunction.

Diagnosis: No evidence of a compressive cord lesion; exclusion of a compressive cord lesion by MRI and confirmation of inflammation by either gadolinium-enhanced MRI or lumbar puncture.

When inflammation is evident in the absence of cord compression, one must evaluate for the presence of infection, systemic inflammation, and the extent and sites central nervous system inflammation.

Acute idiopathic TM: high-dose intravenous glucocorticoid treatment.

Most patients with idiopathic TM have at least a partial recovery, which usually starts within one to three months and continues with exercise and rehabilitation therapy. Some degree of persistent disability is common, and is seen in nearly 40% of the individuals. A very rapid onset with complete paraplegia and spinal shock has been associated with poorer outcomes. Recovery can proceed over years.

Majority of patients with TM have monophasic disease. Recurrence can occur in approximately 25 to 33% of patients with idiopathic TM. With secondary TM, the recurrence rate may be nearly 70%.

Patients presenting with acute complete transverse myelitis have a risk of multiple sclerosis of only 5 to 10%. However, for patients with partial myelitis as the initial presentation and cranial MRI abnormalities showing lesions typical for multiple sclerosis, the transition rate to multiple sclerosis over three to five years is 60 to 90%. Patients with acute partial myelitis with normal brain MRI develop multiple sclerosis at a rate of only 10 to 30% over a similar time period.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA