“The highest levels of the NIH are very concerned,” said Dr. Avindra Nath, intramural clinical director and head of viral research at the National Institute for Neurological Disorders and Stroke, an NIH department. “Everyone’s hope is for a vaccine, and if you have a major complication, it can all be derailed.”
There is still a great deal of uncertainty about what happened to the unnamed patient, to the frustration of those eagerly following the progress of vaccine testing. AstraZeneca, which runs the global trial of the vaccine it produced with Oxford University, said trial volunteers recovered from a severe inflammation of the spinal cord and are no longer hospitalized.
AstraZeneca has not confirmed that the patient was afflicted with transverse myelitis, but Nath and another neurologist said they understood this was the case. Transverse myelitis produces a set of symptoms involving inflammation along the spinal cord that can cause pain, muscle weakness and paralysis. The UK̵
AstraZeneca “needs[s] to be more forthcoming with a potential complication of a vaccine that will eventually be given to millions of people, “Nath said. We want to see how we can help, but the lack of information makes it difficult to do so. “
Any decision as to whether to continue the trial is complex because it is difficult to assess the cause of a rare injury that occurs during a vaccine trial – and because researchers and authorities must weigh the risk of unusual side effects against a vaccine that can slow down the pandemic . .
“So many factors go into these decisions,” Nath said. “I’m sure everything’s on the table. The last thing you want to do is hurt healthy people.”
The NIH has not yet received tissue or blood samples from the British patient and its investigation is “in the planning stage,” Nath said. U.S. researchers could look at samples from other vaccinated patients to see if any of the antibodies they generated in response to coronavirus also attack brain or spinal cord tissue.
Such investigations could take a month or two, he said. The FDA declined to comment on how long it would take before deciding whether to proceed.
Dr. Jesse Goodman, a professor at Georgetown University and a doctor who was chief researcher and chief vaccine regulator at the FDA during the Obama administration, said the agency would review the data and possibly consult with UK regulators before allowing the resumption of the US investigation, which had just begun , when the injury was reported. Two other coronavirus vaccines are also in late-stage trials in the United States
If it determines that the damage in the UK trial was caused by the vaccine, the FDA could suspend the trial. If it allows resumption, regulators and researchers will certainly be on guard for similar symptoms in other trial participants.
A volunteer in an earlier phase of the AstraZeneca trial experienced a similar side effect, but investigators discovered she had multiple sclerosis that was not related to the vaccination, according to Dr. Elliot Frohman, Director of the Multiple Sclerosis & Neuroimmunology Center at the University of Texas.
Neurologists studying diseases such as transverse myelitis say they are rare – occurring at a rate of perhaps 1 in 250,000 people – and most often strike as a result of the body’s immune response to a virus. Less frequently, such episodes have also been linked to vaccines.
The exact cause of the illness is the key to the authorities’ decision on whether to resume the trial. Sometimes an underlying medical condition is “unmasked” by a person’s immune response to the vaccine, leading to illness as it happened to the MS patient. In that case, the experiment can be continued without fear because the disease was not specific for the vaccine.
More troubling is a phenomenon called “molecular imitation.” In such cases, some small piece of the vaccine may resemble 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 incidence of transverse myelitis would likely be if the trial is resumed, Drs. William Schaffner, a specialist in infectious diseases at Vanderbilt University School of Medicine. Another case would close the trial, he said.
In 1976, a massive swine flu vaccination program was halted 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 if the episodes were related to the vaccine.
“It’s very, very difficult” to determine if a rare event was due to a vaccine, Schaffner said. “How do you attribute an increased risk to something that occurs in one in a million people?”
Before the FDA allows U.S. trials to be restarted, the FDA will see why the company and an independent data and safety monitoring committee (DSMB) in the UK felt it was safe to continue, Goodman said. The AstraZeneca trial in the United States has a separate security committee.
FDA officials will have to review all the details of the case and may request additional information about the affected investigation volunteer before deciding whether to continue the U.S. lawsuits, Goodman said. They may also require AstraZeneca to update the safety information it provides to study participants.
It is possible that the volunteer’s health problem was a coincidence that was not related to the vaccine, said Dr. Amesh Adalja, senior researcher at the Johns Hopkins Center for Health Security. Studies are not usually stopped over a single health problem, even if it is serious.
Still, many health executives have expressed frustration that AstraZeneca has not released more information about the health problem that caused it to halt its UK trial.
“There is just so little information about this that it is impossible to understand what the diagnosis was or why the DSMB and sponsor were reassured,” that it was safe to continue, Goodman said.
AstraZeneca has said it is unable to provide more information about the health issue and says this would violate the patient’s privacy, although it did not say how.
But there is an extraordinary need for transparency in a political climate filled with vaccine hesitation and mistrust of the Trump administration’s handling of the COVID-19 response, leading researchers say.
“While respecting the critical need for patient confidentiality, I think it would be helpful to know what their assessment of these issues was,” Goodman said. “What was the diagnosis? If there was no clear diagnosis, what made them feel that the trial could be restarted? There is so much interest and potential concern about a COVID-19 vaccine that the more information that may be provided , the more reassuring it would be. “
The FDA will have to weigh any risks from an experimental vaccine with the danger of COVID-19, which has killed nearly 200,000 Americans.
“There are also potential consequences if you stop an investigation,” Goodman said.
If the AstraZeneca vaccine fails, the US government will support six other COVID vaccines in the hope that at least one will be successful. The potential problems with the AstraZeneca vaccine show that this is a wise investment, Adalja said.
“This is part of the idea of not just having a vaccine candidate going forward,” he said. “It gives you a little more insurance.”
Schaffner said researchers need to remember that vaccine research is unpredictable.
“Investigators have inappropriately hyped their own vaccine,” Schaffner said. “Oxford investigators were out there this summer saying, ‘We’ll get there first.’ But that’s exactly the kind of reason … [Anthony] Fauci and the rest of us have said, ‘You never know what will happen once you get into big human trials.’ “