'Vaccine Makers to Study Rare Post-Vax Syndrome, Spike Persistence After COVID Shot'

 In an unusual move, the FDA asked vaccine makers to conduct randomized studies evaluating possible long-term effects of the COVID-19 shot, including spike persistence and post-vaccination syndrome symptoms.

In the approval letteropens in a new tab or window for the latest versionopens in a new tab or window of the Pfizer (Comirnaty) COVID-19 vaccine, the FDA requested an exploratory, placebo-controlled study to assess whether circulating SARS-COV-2 spike antigen persisted and whether self-reported symptoms of post-COVID-19 vaccination syndrome or long COVID emerged at months 1, 3, 6, and 12 in vaccine and control arms.

In decisional memosopens in a new tab or window for the updated Moderna (Spikevax, mNexspike) and Novavax (Nuvaxovid) shots, the FDA's Center for Biologics Evaluation and Research (CBER) Director Vinay Prasad, MD, MPH, outlined why the CBER Office of the Director (OCD) requested this kind of post-marketing commitment.

"First, there is growing clinical evidence that spike protein which is generated as a result of, or in the course of, vaccination may persist for some time in a subset of individuals," Prasad wrote.

"Second, the symptoms of long COVID or the post-acute COVID syndrome are ill-defined but concern many Americans. Third, there is a fraction of people (note: this does not include CBER OCD) who believe there is a link between these two," he continued.

"As such, CBER OCD believes it has an obligation to Americans to request the Applicant generate information which may link or exculpate any such relationship. If a real, positive association is present in randomized fashion, it would constitute a concerning finding," Prasad added.

"CBER OCD also notes that this substudy design may also be able to adjudicate if annual COVID-19 vaccines reduce long COVID symptoms, a claim that FDA has never permitted the applicant to make, depending on power."

Earlier this year, a small studyopens in a new tab or window identified potential immunologic patterns associated with post-vaccination syndrome, a very rare condition with neurologic symptoms that occurs in some people following a COVID-19 vaccine.

In findings posted in February on the preprint server medRxivopens in a new tab or window without peer-review, Akiko Iwasaki, PhD, of Yale University School of Medicine in New Haven, Connecticut, and colleagues noted a small fraction of the population reported a chronic debilitating condition after COVID-19 vaccination that is often referred to as post-vaccination syndrome.

The immune cell populations of people with post-vaccination syndrome were different from healthy controls, Iwasaki and co-authors noted.

A subset of post-vaccination syndrome patients also had higher levels of circulating spike protein in their blood, they showed. Detectable levels of the S1 subunit of the spike protein were seen in plasma up to 709 days after the most recent known exposure.

In 2023,opens in a new tab or window a surveyopens in a new tab or window led by Harlan Krumholz, MD, also of Yale, suggested that people who experienced rare long-term adverse events after COVID-19 vaccination often had neurologic symptoms.

Of 241 survey participants who self-reported a post-vaccination syndrome, the five most common symptoms were exercise intolerance (71%), excessive fatigue (69%), numbness (63%), brain fog (63%), and neuropathy (63%). The survey data were posted on medRxivopens in a new tab or window and have not been peer-reviewed.

Reports to the Vaccine Adverse Event Reporting System (VAERS) after COVID vaccination also include a variety of neurologic and systemic manifestations, Krumholz and co-authors noted at the time.

These symptoms may share mechanisms with post-COVID complications, they observed. "Importantly, immune-mediated neurological adverse events post-vaccination are rare and often less severe than those that follow actual infection," they wrote.

Large observational studies from researchers in Norwayopens in a new tab or window and othersopens in a new tab or window suggested that COVID-19 vaccines may prevent long COVID symptoms or reduce symptom severity. Data from the U.S. Department of Veteran Affairsopens in a new tab or window also indicated that lower long COVID rates may be attributable in part to vaccines.

The CDC recommended vaccination to preventopens in a new tab or window long COVID.

https://www.medpagetoday.com/neurology/generalneurology/117311