Are mRNA Covid Vaccines Risky? Here’s What the Experts Say

(Bloomberg) -- When it became clear in early 2020 that the Sars-CoV-2 virus posed a pandemic threat, researchers who’d been exploring an innovative way to make vaccines saw an opportunity. Experimental messenger RNA vaccines, seen for years as potentially offering speed and flexibility to combat a fast-moving epidemic, were some of the first Covid-19 inoculations to move into human trials. The effort paid off when, late last year, vaccines from Moderna Inc. and the Pfizer Inc./BioNTech SE partnership were the first to demonstrate efficacy. Their performance has raised hopes among scientists that mRNA technology will prove useful against other diseases. Because the platform is so new, however, mRNA vaccines are particularly vulnerable to disinformation campaigns aimed at dissuading people from taking the shots.

1. How do mRNA vaccines work?

Instead of introducing the body to an inactivated or weakened version of a virus or a piece of it, like previous generations of vaccines, they temporarily turn the body’s cells into tiny vaccine-making factories. They do this using synthesized versions of something called messenger RNA, a molecule that normally carries genetic coding from a cell’s DNA to its protein-making machinery. In the case of Covid vaccines, the mRNA instructs the body to make the spike protein that Sars-CoV-2 uses to enter cells. This, in turn, stimulates the body to make high levels of antibodies to the virus. Messenger RNA vaccines are quicker to develop than traditional ones because their production doesn’t require growing viruses or viral proteins inside live cells. It took researchers just a few days in January 2020 to come up with the mRNA sequence used in Moderna’s Covid vaccine.

2. What do we know about their efficacy?

Although there have been no head-to-head clinical trials, it appears from evidence gathered in studies before and after the vaccines were authorized that the mRNA versions are superior to the other formulations in widespread use. Moderna’s vaccine was 94% effective at preventing Covid, that is to say, a symptomatic case of coronavirus infection, and Pfizer-BioNTech’s was 95% effective in the trials resulting in their authorization. Those numbers are under assault with the subsequent spread of the delta variant of SARS-CoV-2, which appears to be better than earlier strains at evading immunity gained from vaccination. Still, data out of New York state show that the vaccines have remained highly protective against hospitalization, even during the period where delta took over.

3. What do we know about their safety?

Both vaccines can induce strong versions of fairly typical reactions to inoculation generally, including headaches, muscle and joint pain, and fever, especially after the second shot. The shots have been connected to rare cases of severe allergic reactions which generally can be treated with adrenaline, although a small minority of cases required insertion of a tube into the windpipe to help with breathing. It’s thought likely that mRNA vaccines have triggered cases of inflammation in the heart and heart lining of some recipients, mostly younger people. The risk of this reaction is extremely low, most cases are mild, and people often recover with no or minimal treatment, according to U.S. health officials. After getting Moderna’s vaccine, some people get delayed rashes that are sometimes dramatic but not dangerous.

4. Who’s spreading disinformation about the vaccines?

Traditional anti-vaccine activists have increasingly joined forces with figures on the alt-right, a primarily online political movement based in the U.S. whose members espouse extremist beliefs typically centered on ideas of white nationalism. High-profile conservatives including Fox News personality Tucker Carlson have raised doubts about Covid vaccines generally. According to the U.S. State Department, several online platforms linked to Russian Intelligence have spread disinformation about mRNA vaccines; Moderna and Pfizer are U.S.-based companies. A Kaiser Family Foundation survey found that vaccine refusers are disproportionately reliant on Facebook for their information, whereas people who want the vaccine are more likely to read newspapers or watch network TV news.

5. What are they saying?

• That steps were skipped in developing and authorizing the vaccines: It’s true that the vaccines reached the market in record time, but that’s not because any testing steps were skipped. Companies sped up the process by performing some stages in parallel, and, in the case of Moderna’s vaccine, the U.S. government took financial risks by paying to gear up manufacturing before results were in.
• The vaccines were rolled out before getting approval from the Food and Drug Administration: That’s true in the sense that the agency initially gave only emergency-use authorization. This is a pre-existing mechanism created to speed access to medical countermeasures in the event of a public health emergency such as the Covid pandemic. The FDA established in advance that to win authorization, Covid vaccines had to prove to be at least 50% effective in preventing illness in large-scale trials and had to demonstrate safety with two months’ of follow-up data on trial participants. Also, the vaccines were vetted by a panel of independent advisers. The Pfizer-BioNTech vaccine received full FDA approval in August, and Moderna’s application is under consideration.
• Critics have taken to labeling mRNA vaccines a form of gene therapy, insinuating that the shots might somehow alter your DNA: They don’t. While the messenger RNA they employ is a type of genetic material, the vaccines differ from what is typically thought of as gene therapy in that they do not change the DNA inside cells. “They do not affect or interact with our DNA in any way,” the Centers for Disease Control and Prevention explains. In fact, mRNA molecules in the vaccines, which are short-lived, don’t enter the nucleus of cells, where DNA is stored, the CDC notes.
• That the lipid nanoparticles that coat the vaccines, helping carry them into the body, may contain antifreeze: That’s not true. Antifreeze contains ethylene glycol, which is toxic. The lipid nanoparticles instead include polyethylene glycol, an inert compound found in everyday products like toothpaste and shampoo and in many drugs including laxatives.
• That the vaccines can cause antibody-dependent enhancement, or a worse case of disease in those who become sick despite inoculation: This was a theoretical concern when testing of Covid vaccines began. There were hints of this problem in animal studies of some vaccines for severe acute respiratory syndrome (SARS), which is caused by a coronavirus related to SARS-CoV-2. However, no indication of this emerged in human trials of mRNA vaccines for Covid, according to Stanley Perlman, a coronavirus researcher at the University of Iowa, who served on the FDA advisory panel that reviewed the vaccines.
• That we don’t know the long-term effects of the vaccines: That’s always the case with new vaccines. But side effects usually show up within the first couple of months after vaccination, which is why the FDA insisted on two months of safety data before authorizing them. Now there are months more data on the vaccines, with no safety showstoppers, other than the uncommon cases of heart and heart lining inflammation.
• That there are more adverse event reports for Covid vaccines than there have been for influenza vaccines: That’s not an appropriate or meaningful comparison, says Aaron Kesselheim, a professor of medicine at Harvard Medical School. The number of these reports tends to surge when a treatment or vaccine is in the news, and nothing has been more in the headlines than Covid vaccines. In the U.S., these reports can be filed by anyone and don’t constitute confirmation that a vaccine caused an adverse event. Given the large numbers being inoculated, some unlucky people will get sick and even die shortly after getting shots, regardless of the vaccine.

6. How might mRNA be useful for other vaccines?

Once an mRNA vaccine proves effective, in theory researchers can quickly tweak it to combat a different virus by changing the genetic code they put into the mRNA. Obvious targets include the 50 or so new viruses that have infected humans in the last 40 years for which there are no vaccines as well as hard-to-target pathogens such as HIV. Researchers also hope mRNA vaccines can improve on existing versions of flu shots, which must sometimes begin production six months in advance based on experts’ assessment of which strains of flu virus are likely to circulate. The hope is that the shorter lead times required to make mRNA shots would enable health officials to more closely match them to flu strains and improve upon typical efficacy rates of 40% to 60%.

7. What about broader applications? 

Enthusiasts suggest the technology will produce a new industry capable of treating almost everything from heart disease to cancer to rare genetic conditions. That’s because, in theory, mRNA could be used to prompt cells in the body to produce any protein -- not just a so-called antigen that generates antibodies to fight infection but also an enzyme to reverse disease, or growth agents to repair damaged tissue.

8. What are the caveats?

It’s an open question whether there would be a good economic case for mRNA-based flu vaccines if they turn out to be more expensive and only modestly better than existing ones. The mRNA Covid shots have complicated refrigeration requirements, which increase the cost of deploying them. To expand beyond vaccines into the far larger and more lucrative therapeutics market will require surmounting additional technical hurdles. To treat chronic diseases, for example, companies will have to prove that they can safely deliver the therapies to the target organs. And to develop cancer vaccines, mRNA researchers will have to solve the thorny problem of teaching the immune system to distinguish between specific tumors and healthy cells. Many previous approaches have failed. 

The Reference Shelf

• Related QuickTakes on vaccine reactions, how Covid vaccines are performing, Covid vaccine hesitancy, and the anti-vaccine movement.
• A Bloomberg Businessweek article explores the partnership between Moderna and BioNTech that produced one of the first authorized Covid vaccines.
• An article in Stat examines the history and promise of mRNA technology.

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