Five years after their initial rollout, scientists have pinpointed the cause of a rare heart inflammation – myocarditis – linked to mRNA coronavirus vaccines. A new study, published Wednesday in Science Translational Medicine, identifies a complex interaction between immune cells as the trigger for these cases, which occurred in less than one in 10,000 vaccine recipients, primarily young men. Researchers have also identified genistein, a phytoestrogen, as a potential treatment, offering a crucial step forward in understanding and mitigating this uncommon side effect of the groundbreaking mRNA technology.
Scientists are gaining clarity on a rare side effect linked to the first mRNA coronavirus vaccines, five years after their initial rollout. The vaccines, a breakthrough in preventative medicine, prompted a small number of cases – less than one in 10,000 – of myocarditis, or inflammation of the heart muscle, primarily in young men shortly after vaccination.
Researchers at Stanford and Harvard Universities have identified a complex interplay between macrophages and T-cells reacting to the foreign genetic material as the cause of this uncommon adverse event. Their findings, published Wednesday in Science Translational Medicine, also detail a potential treatment to mitigate the reaction: genistein, a phytoestrogen.
The mRNA vaccines from Pfizer and Moderna, widely used during the pandemic, represented a novel approach to immunization. These vaccines deliver a snippet of synthetic genetic code containing instructions for building the spike protein found on the surface of the SARS-CoV-2 virus. This prompts the body’s cells to produce the protein, training the immune system to recognize and defend against the virus. The vaccines proved highly effective in preventing severe illness and death from COVID-19.
Following widespread vaccination campaigns in 2021, several hundred cases of myocarditis were reported to Lareb, the Netherlands pharmacovigilance center. Those affected experienced symptoms such as shortness of breath, fever, chest pain, and palpitations. While most cases were mild and temporary, the risk of myocarditis was notably higher in individuals who remained unvaccinated and contracted COVID-19. The side effect was subsequently added to the vaccine’s official information leaflet, but the underlying cause remained elusive.
Immune System Alarm Signals
The American research team conducted a thorough investigation of the underlying mechanisms. Analyzing data from two previous studies of Pfizer vaccine recipients, with and without reported symptoms, they identified two signaling molecules elevated in the blood of those experiencing adverse effects: CXCL10 and interferon-gamma. These cytokines act as alarm signals within the immune system, triggering an inflammatory response.
Building on this knowledge, the researchers conducted experiments using cultured immune cells and mice. They discovered that macrophages, a type of immune cell that often responds first to threats, produced significant amounts of CXCL10 when exposed to the mRNA vaccine. Subsequently, they found that T-cells, a type of white blood cell, reacted to this signal by releasing large quantities of interferon-gamma.
Experiments with mice demonstrated that vaccination could induce heart inflammation, and that this effect could be replicated by administering a combination of the two signaling molecules. Blocking the function of CXCL10 or interferon-gamma with molecular inhibitors significantly reduced the inflammation.
Joseph Wu, a member of the research team, previously worked with genistein, a phytoestrogen derived from soy. His earlier research showed that the compound could limit blood vessel and heart damage associated with heavy cannabis use, attributing the effect to its anti-inflammatory properties. The team decided to test genistein in their myocarditis research, hypothesizing a potential hormonal component to the side effect, given its prevalence among young men. Their mouse studies confirmed that genistein could indeed dampen heart inflammation following vaccination.
The authors emphasize that their research has implications beyond the Pfizer and Moderna COVID-19 vaccines, extending to all current and future mRNA vaccines. The introduction of mRNA carries a potential, albeit rare, risk of triggering a transient inflammatory response, not only in the heart but potentially in other organs as well. This finding underscores the importance of continued monitoring and research into mRNA vaccine safety and efficacy.
NEW: Give this article as a gift
As an NRC subscriber, you can give 10 articles each month as a gift to someone without an NRC subscription. The recipient can read the article directly, without a paywall.
The journalistic principles of NRC
