By Peter Chow
The participant who triggered a global shutdown of AstraZeneca’s Phase 3 Covid-19 vaccine trials was a woman in the United Kingdom who experienced neurological symptoms consistent with a rare but serious spinal inflammatory disorder called transverse myelitis, the drug maker’s chief executive, Pascal Soriot, said during a private conference call with investors.
The board tasked with overseeing the data and safety components of the AstraZeneca clinical trials confirmed that the participant was injected with the company’s Covid-19 vaccine and not a placebo.
Soriot also confirmed that the clinical trial was halted once previously in July after a participant experienced neurological symptoms. Upon further examination, that participant was diagnosed with multiple sclerosis, deemed to be unrelated to the Covid-19 vaccine treatment, he said.
To date, AstraZeneca’s public statements on the pause have been sparse with details. For instance, the company has not publicly confirmed that this is the second time its trials have been stopped to investigate health events among participants.
The vaccine — known as AZD1222 — uses an adenovirus that carries a gene for one of the proteins in SARS-CoV-2, the virus that causes Covid-19. The adenovirus is designed to induce the immune system to generate a protective response against SARS-2. The platform has not been used in an approved vaccine, but has been tested in experimental vaccines against other viruses, including the Ebola virus.
Transverse myelitis (TM) is a neurological condition in which the spinal cord is inflamed. Transverse implies that the inflammation extends horizontally across the spinal cord. The “pathological hallmark” of the condition is the “focal collection of lymphocytes and monocytes with varying degrees of demyelination, axonal injury and astroglial and microglial activation within the spinal cord.”
Transverse myelitis is a serious condition that can cause sensory loss, muscle weakness, paralysis, pain and bladder and bowel problems. Vaccines have triggered cases of transverse myelitis; it can also be caused by viral and bacterial infections, immune system disorders, and demyelinating diseases (MS).
Viral infections known to be associated with TM include HIV, herpes simplex, herpes zoster, cytomegalovirus, Epstein-Barr, Zika virus and West Nile virus.
Bacterial causes associated with TM include Mycoplasma pneumoniae, Campylobacter jejuni, and Borrelia burgdorferi which causes Lyme disease. Lyme disease gives rise to 5% of acute transverse myelitis cases.
Association of transverse myelitis with viral and bacterial infections could result from the infection itself or from the immune response to it.
The concern with vaccine etiology is a phenomenon called “molecular mimicry.” In such cases, some small piece of the vaccine may be similar to tissue in the brain or spinal cord, resulting in an immune attack on that tissue in response to a vaccine component.
Should that be the case, another occurrence of transverse myelitis would be likely if the trial resumed, said Dr. William Schaffner, an infectious disease specialist at the Vanderbilt University School of Medicine. A second case would shut down the trial, he said.
In 1976, a massive, rushed, emergency Swine Flu vaccination program was halted abruptly when doctors began diagnosing a similar disorder, Guillain-Barré syndrome, in people who received the vaccine. At the time no one knew how common GBS was, so it was difficult to tell whether the episodes were related to the vaccine.
Eventually, scientists found that the vaccine increased the risk of the disorder by an additional one case among every 100,000 vaccinated patients. Typical seasonal flu vaccination raises the risk of GBS in about one additional case in every 1 million people.
“It’s very, very hard” to determine if one rare event was caused by a vaccine, Schaffner said. “How do you attribute an increased risk for something that occurs in one in a million people?”
Rare complications of any vaccine, if there are any, may not turn up until it has been administered to hundreds of thousands or even millions of people.
Schaffner said researchers need to remember that vaccine research is unpredictable.
“The investigators have inadvisedly been hyping their own vaccine,” Schaffner said. “The Oxford investigators were out there this summer saying, ‘We’re going to get there first.’ But this is exactly the sort of reason … Dr. [Anthony] Fauci and the rest of us have been saying, ‘You never know what will happen once you get into large-scale human trials.'”