NIH ‘Concerned’ about Side Effects in Coronavirus Vaccine Trial

The National Institutes of Health has launched an investigation into the case of a patient with spinal cord damage after being involved in AstraZeneca’s coronovirus vaccine trial.

The international trial came to a halt last week when the participant’s illness was revealed. Oxford University, which is developing the vaccine along with AstraZeneca, said over the weekend that British regulators had allowed the trial to resume in the United Kingdom. The US Food and Drug Administration is weighing whether to follow suit.

“The highest levels of NIH are very concerned,” Dr. Said Avindra Nath, intramural clinical director and a leader in viral research at the National Institute for Neurological Disorders and Stroke, a division of the NIH. “Everyone’s expectations are on a vaccine, and if you have a big complication the whole thing can derail.”

There remains a great deal of uncertainty about what happened to the anonymous patient. AstraZeneca said that Trial Volunteer, who recovered from severe spinal cord inflammation, is no longer hospitalized.

Nath and another neurologist said they understand that the patient was suffering from transverse myelitis, although the company has not confirmed it. Transverse myelitis produces symptoms associated with inflammation along the spine that can cause pain, muscle weakness, and paralysis.

AstraZeneca “needed[s] Nath said, to come forward with the potential complication of a vaccine that would eventually be given to millions. “We would like to see how we can help, but the lack of information makes it difficult to do so.”

The Medicines and Healthcare Products Regulatory Agency, a UK regulatory body, reviewed the case before deciding to resume testing on sites in the UK.

Any decision on whether to continue is bound to be complicated. It is difficult to assess the cause of a rare injury occurring in a clinical trial. In addition, scientists and health officials have to weigh the risk of unusual side effects against the benefits of a vaccine with the potential to curb a deadly global epidemic.

“So many factors go into these decisions,” Nath said. Still, he said, “The last thing you want to do is hurt healthy people.”

The NIH is yet to receive tissue or blood samples from a British patient, and its investigation is “in the planning stages”, Nath said.

US scientists can look at samples from other vaccinated patients to see if any antibodies generated in response to coronovirus attack the brain or spinal cord tissue. He said that such studies may take one or two months.

The FDA declined to comment on how long it would take before proceeding.

A Georgetown University professor and physician, Dr. Jesse Goodman, who was the chief scientist and principal vaccine regulator at the FDA during the Obama administration, said the agency would review the data and possibly consult with British regulators before being allowed to resume the US study. The bus started as soon as the injury was reported. Two other coronavirus vaccines are also in late trials in the US

If the FDA allows the AstraZeneca trial to be resumed, regulators and scientists will certainly monitor similar symptoms in other trial participants.

A volunteer experienced a similar side effect in the first phase of testing, but investigators found that he had multiple sclerosis that was unrelated to vaccination, Dr. Texas Director of Multiple Sclerosis and Neuromycology Center at the University of Texas. According to Elliot Frohman.

Neurologists studying diseases such as transverse myelitis say they are rare – perhaps at a rate of 1 in 250,000 people – and strike the most frequently as a result of the body’s immune response to the virus. Less often, such episodes have also been linked to vaccines.

The exact cause of the study participant’s illness is important to the decision by the authorities as to whether to resume testing. Sometimes an underlying medical condition is “unmasked” by a person’s immune response to the vaccine and leads to the disease that occurred with the MS patient. In that case, the test may be continued without fear, as the disease was not specific to the vaccine.

More worrying is a phenomenon known as “molecular mimicry”. In such cases, some small pieces of the vaccine may resemble tissue in the brain or spinal cord, resulting in an attack of the immune system on that tissue in response to a vaccine component.

If this is the case, there will be another possibility of transverse myelitis if the trial resumes, Drs. William Scheffner, an infectious disease specialist at Vanderbilt University School of Medicine. A second case will close the trial.

In 1976, the massive swine flu vaccination program was halted when doctors began diagnosing Guillain-Barre syndrome, a similar disorder in people receiving the vaccine. At the time no one knew how common GBS was, so it was difficult to tell whether the episodes were vaccine-related.

Eventually, scientists found that the vaccine increased the risk of the disorder There is an additional case among every 100,000 vaccinated patients. Specific seasonal flu vaccination increases the risk of GBS in approximately one additional case per 1 million people.

“It’s very, very difficult” to determine whether a rare event was caused by a vaccine, Scheffner said. “How can you increase the risk of one in a million people?”

Goodman said that before allowing US trials to resume, the FDA would like to see why the company and an independent Data and Safety Monitoring Board, or DSMB, continue in the UK. (In the United States, the AstraZeneca test has a separate safety board.)

FDA officials will need to review the full details of the case and may request more information about the affected study volunteer before making a decision, Goodman said. They may also require AstraZeneca to update the security information provided to the participants to study.

It is possible that the volunteer’s health problem was unrelated to the vaccine, a senior scholar at the Johns Hopkins Center for Health Security, Dr. Amesh Adalja said. Studies are usually not discontinued on a single health problem, even if it is severe.

Yet many health leaders have expressed disappointment that AstraZeneca has not released much information about the health problem that has led to its UK trial being halted.

“There is little information about whether it is impossible to understand what the diagnosis was or why DSMB and the sponsor were convinced” it was safe to continue, Goodman said.

AstraZeneca has said that it is unable to provide more information about the health problem. Doing so would violate patient confidentiality, the drugmaker said, though did not say how.

Scientists say there is an extraordinary need for transparency in a political environment with hesitation of the vaccine and mistrust of the Trump administration’s response, which is a response to COVID-19.

“Although I respect the critical need for patient privacy, I think it would be really useful to know what their assessment of these issues was,” Goodman said. What was the diagnosis? If there was no clear diagnosis, what made them think the test could be resumed? There is so much interest and potential concern about the COVID-19 vaccine that the more information that can be provided, the more reassuring it will be. ”

The FDA will need to balance any potential risk from the experimental vaccine with the threat posed by COVID-19, which has killed approximately 35,000 Americans.

“If you stop a study, it also has potential consequences,” said Goodman.

If the AstraZeneca vaccine fails, the US government is supporting six other COVID vaccines in the hope that at least one will be successful. Adalja said the potential problems with the AstraZeneca vaccine is a wise investment.

“It’s just part of the idea of ​​not going beyond a vaccine candidate,” he said. “It gives you a little more insurance.”

Scheffner said that researchers need to remember that vaccine research is unpredictable.

“Investigators have inadvertently hypnotized their own vaccine,” Scheffner said. “Oxford investigators this summer were saying, ‘We’re going to get there first.’ But this is exactly like the reason… Dr. [Anthony] Fauci and the rest of us have been saying, ‘You never know what will happen in a large-scale human trial. ”

Arthur Allen and Liz Szabo writes for Kaiser Health News, A non-profit news service covering health issues. This is an editorial independent program Kaiser Family Foundation It is not affiliated with Kaiser Permanente.

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