Only One Harm From mRNA COVID Vaccines, Report Determines

Independent reviewers confirmed a causal relationship between the first mRNA COVID-19 vaccines and myocarditis, and also determined that, more broadly, intramuscular shots can cause a series of shoulder injuries.

At the same time, the National Academies of Sciences, Engineering, and Medicine (NASEM) committee rejected a causal relationship between the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 (Comirnaty and Spikevax, respectively) mRNA COVID vaccines and female infertility, Guillain-Barré syndrome, Bell's palsy, thrombosis with thrombocytopenia syndrome (TTS), and myocardial infarction.

The evidence was also deemed enough to reject a causal link between the Pfizer vaccine and ischemic stroke. There was insufficient data to say the same for the Moderna one, however, according to a report commissioned by the Health Resources and Services Administration (HRSA), a subagency of the HHS.

"Despite a large body of evidence from extraordinary efforts by investigators around the world, our committee found that in many cases, if not most, evidence was insufficient to accept or reject causality for a particular potential harm from a specific COVID-19 vaccine," said committee vice chair Anne Bass, MD, of Weill Cornell Medicine, Hospital for Special Surgery, and New York-Presbyterian Hospital, New York City, in a press release.

"In other cases, we did find sufficient evidence to favor rejection, favor acceptance, or establish causality. It is important to note, however, that identifying a harm does not mean that it occurs frequently," she cautioned. "Harms associated with vaccines are rare."

HRSA had requested this review from NASEM, an independent nonprofit, in order to address claims for compensation under its Countermeasures Injury Compensation Program. This federal program provides compensation related to injuries from pandemic, epidemic, or security countermeasures.

The link between the mRNA vaccines and myocarditis has been probed in many studies since initial reports were logged into the voluntary Vaccine Adverse Event Reporting System (VAERS) in April 2021. Reports consistently described myocarditis associated with COVID vaccines as mostly mild. Detailed records showed that affected vaccine recipients tended to be men and adolescent boys who were typically able to recover after a few days in the hospital.

The feared spike in sudden cardiac deaths among affected individuals with myocarditis has not been realized. For example, a recent study from Oregon reported no excess sudden cardiac deaths among young people soon after COVID-19 mRNA vaccination.

"Given that the studies we reviewed were performed shortly after vaccines were available, the information in this report is a snapshot in time, and new vaccines will be developed and more research conducted," said committee chair George Isham, MD, of HealthPartners Institute in Minnesota.

"For example, the evidence does not address the real-world use of the COVID-19 vaccines in which many individuals received a 'mix and match' sequence of them. Many people vaccinated for COVID-19 also received other vaccines, such as influenza, simultaneously," Isham added in a statement.

In 2022, Pfizer and Moderna had their first-generation mRNA COVID vaccines replaced by bivalent versions blending protection against the ancestral COVID strain and the Omicron BA.4/5 subvariants circulating at the time. They were not as widely adopted as the original vaccines, and initially suspected of a potential stroke risk until suspicion turned to high-dose or adjuvanted flu shots instead.

The bivalent vaccines remained available until the arrival of monovalent vaccines targeting the XBB.1.5 Omicron subvariant for the 2023-2024 respiratory virus season.

For its present report, NASEM also reviewed the evidence for two other COVID-19 vaccines, the Johnson & Johnson (J&J) adenovirus vector vaccine (Ad26.COV2.S) and the Novavax protein-based vaccine (NVX-CoV2373).

The verdict: the J&J vaccine may cause TTS and Guillain-Barré syndrome (this vaccine was withdrawn from the market in 2023) while evidence for the Novavax shot was insufficient to accept or reject a causal relationship with any of the 19 side effects of interest.

Beyond those already noted, the side effects investigated included chronic inflammatory demyelinating polyneuropathy; transverse myelitis; chronic headache; postural orthostatic tachycardia syndrome; sensorineural hearing loss; tinnitus; immune thrombocytopenic purpura; capillary leak syndrome; hemorrhagic stroke; deep vein thrombosis, pulmonary embolism, or venous thromboembolism; pericarditis without myocarditis; and sudden death.

A more general investigation also established a general causal relationship between intramuscular administration of routinely administered vaccines and various shoulder injuries:

• Subacromial/subdeltoid bursitis caused by direct injection into the bursa
• Acute rotator cuff or acute biceps tendinopathy caused by direct injection into or adjacent to a tendon
• Bone injury caused by direct injection into or adjacent to the bone
• Axillary or radial nerve injury caused by direct injection into or adjacent to the nerve

The NASEM reviewers acknowledged that there was not enough evidence for conclusions to be made about potential harms to children, especially children under age 11.

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