COVID-19 mRNA Vaccines: Understanding the Potential Risks and What the Research Shows

Why Was the Safety of COVID-19 mRNA Vaccines Questioned?

On December 6, 2023, Dr. Joseph A. Ladapo, Florida State Surgeon General, wrote a letter to the heads of two important health organizations. He had questions about the safety of the Pfizer and Moderna COVID-19 vaccines.

In simple terms, he was worried about tiny pieces of genetic material in the vaccines. These genetic pieces could be contaminants, and they were found alongside the lipids and other stuff in the vaccines. There was also concern about a specific type of DNA that might pose a risk of integrating into our cells.

Now, does this worry have a basis in science? Let's look at the evidence.

How Do mRNA Vaccines Work?

Exogenous mRNA, which means introducing external genetic material into the body, was first suggested in 1990 for medical purposes [1]. People have become more interested in using this approach to create new RNA-based treatments [2, 3]. Two main types of RNA-based technologies are currently used in medicine: messenger RNA (mRNA) and small interfering RNA (siRNA). These are applied in various ways, such as for cancer treatment, making up for missing proteins, editing genes, and vaccines.

The main idea behind this technology is relatively straightforward: with mRNA, we can give the body instructions to fix a genetic issue by producing a standard version of a protein that might be missing or altered. Additionally, mRNA can instruct the body to create a specific protein that triggers an immune response [4]. On the other hand, siRNA is used to "silence" or turn off genes that are related to diseases in a precise way [5].

The History of mRNA Technology Before COVID-19

Before the COVID-19 pandemic, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) had approved only four RNA-based treatments. These treatments, which use synthetic lipid nanoparticles or chemically modified siRNA, are available commercially to treat rare conditions like acute hepatic porphyria, type I hyperoxaluria, heterozygous familial hypercholesterolemia, and hereditary transthyretin-mediated amyloidosis.

Nearly 30 years ago, scientists discovered that a particular type of genetic material called mRNA could help the body fight off diseases. Before the COVID-19 pandemic, researchers had only tested mRNA vaccines on animals and in the early stages of human testing [6].

What Safety Questions Remain?

In 2020, scientists developed two mRNA-based vaccines in record time due to the urgent need for a COVID-19 vaccine. They were quickly authorized for widespread use. While making fast decisions during emergencies is expected, some precautions should never be skipped, significantly if they could harm people's health. Even in emergencies, we should follow the basic rule of "first, not harm," which is a fundamental principle in medical ethics.

Every medical intervention has potential risks, and before people decide to get the COVID-19 mRNA vaccines, they should be fully informed about what is known and what is still uncertain regarding their safety in the short and long term. This reminder was given to the medical community soon after the vaccines were authorized [7], but it hasn't been consistently communicated to the public in most countries.

We don't know how safe nucleoside-modified synthetic mRNA (nms-mRNA) is. Tests that usually check various safety aspects were skipped, like how the mRNA spreads in the body, gets into cells, and affects different cell types. These tests also usually examine potential interactions with the host's genetic material. One big worry with using nms-mRNA, like in the COVID-19 vaccines, is that these modifications might cause changes in the genetic material of both dividing and non-dividing cells, a concern related to epigenetic and genomic modifications.

What Does the Published Research Say?

Unfortunately, despite lacking much information, many scientific reviews say these vaccines are safe [8, 9, 10]. They argue that there's no risk of the vaccine's genetic material integrating into our genes, as can happen, although rarely, with other types of vaccines. However, it's important to note that before these COVID-19 vaccines were authorized and widely used, no published studies specifically looked into potential issues like changes in chromatin structure, integration into chromosomes, genetic damage, or cancer development caused by these mRNA vaccines. Only one study, which was peer-reviewed, was conducted in the 14 months after the vaccines were authorized, and it showed that the vaccine's mRNA can activate some aspects of our genes, undergo reverse transcription, and enter the cell nucleus [11].

A meeting in early 2020 discussed the safety of COVID-19 vaccines. The report from the meeting didn't have any evidence about the potentially harmful effects of a specific type of mRNA used in these vaccines [12]. The concern is that we don't know if these vaccines can affect our genes or cause cancer. When we look at scientific papers discussing the safety of these mRNA vaccines, they often claim high levels of safety without providing any references or evidence. One review study mentioned that the mRNA used in the vaccines is not likely to integrate into our genes or cause mutations, but it didn't prove this claim [13]. None of the studies cited in that review paper had looked into these vaccines' genotoxicity or cancer-causing potential. The same goes for the human trials – none investigated these potential risks [14].

What is the Proposed Biological Mechanism?

In some people who are more susceptible due to their genes or physiology, removing specific mRNA molecules (called nms-mRNAs) is not working correctly. This causes a continuous presence of these molecules in the cell, which messes up the normal functions of some elements in the cell.

This disruption leads to a process where the vaccine's mRNA is converted backward in the cell. As a result, a bunch of molecules is built inside the cell, triggering the cell's defense mechanisms against these foreign materials. This defense response involves the production of certain substances (like type-I interferon and pro-inflammatory cytokines), which can cause problems if not appropriately controlled. It may lead to conditions where the body starts attacking itself, causing inflammation or even autoimmune diseases.

Furthermore, the activated elements in the cell also increase the risk of changes in the DNA. This can potentially mess up essential parts of the DNA, increase the chances of mutations in specific genes that prevent the growth of tumors, and cause continuous damage to the DNA in the long run [15].

Key Takeaways

Research into mRNA vaccine technology continues to evolve. While many researchers conclude the vaccines have an acceptable safety profile, others argue that additional long-term studies are needed to better understand questions related to biodistribution, genomic effects, and rare adverse events. As with any medical intervention, understanding both the available evidence and its limitations helps readers make informed decisions.