On 6 January 2021, the CDC has issued updated interim guidance for contraindications to Pfizer and Moderna COVID-19 vaccines. As I had discussed previously, the CDC had been focused on an ingredient in both vaccines, polyethylene glycol (PEG), that may cause allergic reactions.
I think it’s important that the CDC and other public health authorities are transparent and speedy about these new COVID-19 vaccines to make certain that contraindications are widely known.
New COVID-19 vaccines contraindications
The CDC issued the following contraindications to vaccinations with both the Pfizer and Moderna COVID-19 vaccines:
Severe allergic reaction (e.g., anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components
Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including polyethylene glycol [PEG])*
Immediate allergic reaction of any severity to polysorbate (due to potential cross-reactive hypersensitivity with the vaccine ingredient PEG)*
- * These persons should not receive mRNA COVID-19 vaccination at this time unless they have been evaluated by an allergist-immunologist and it is determined that the person can safely receive the vaccine (e.g., under observation, in a setting with advanced medical care available).
CDC guidance defined an “immediate allergic reaction” as any hypersensitivity-related signs or symptoms such as urticaria (hives), angioedema, respiratory distress such as wheezing, or anaphylaxis that occur within four hours following exposure.
What is going on with polyethylene glycol?
Polyethylene glycol is a small organic molecule that has numerous uses in medicine including as a laxative (if you’ve ever had a colonoscopy, you will be familiar with it) and as an excipient in many drugs to protect proteins from being cleared quickly from the bloodstream. It is also used in soaps and shampoos.
Even though polysorbate is not an ingredient of either of the COVID-19 vaccines, the CDC has included previous allergies to it in the list of contraindications because there is some evidence that those who are allergic to polysorbate may also be allergic to PEG.
In the Pfizer and Moderna COVID-19 mRNA vaccines, the polyethylene glycol stabilizes the lipid nanoparticles that “surround” the mRNA fragments, keeping them from being destroyed by the body before they can enter the cell and induce the manufacturing of the S-protein antigen of the SARS-CoV-2 virus.
According to a recent report in Science:
Severe allergy-like reactions in at least eight people who received the COVID-19 vaccine produced by Pfizer and BioNTech over the past 2 weeks may be due to a compound in the packaging of the messenger RNA (mRNA) that forms the vaccine’s main ingredient, scientists say. A similar mRNA vaccine developed by Moderna, which was authorized for emergency use in the United States on Friday, also contains the compound, polyethylene glycol (PEG).
PEG has never been used before in an approved vaccine, but it is found in many drugs that have occasionally triggered anaphylaxis—a potentially life-threatening reaction that can cause rashes, a plummeting blood pressure, shortness of breath, and a fast heartbeat. Some allergists and immunologists believe a small number of people previously exposed to PEG may have high levels of antibodies against PEG, putting them at risk of an anaphylactic reaction to the vaccine.
PEG was considered to be biologically inert, but a recent study showed that as many as 72% of people have some antibodies against PEGs, although that does not mean that all of those individuals would be vulnerable to being allergic to PEG. And of those individuals, about 7% may have a level that could predispose individuals to anaphylactic reactions.
Despite this, there are a lot of products with PEG on the market, and we’re just not observing that 7% of the population is experiencing an anaphylactic reaction after using it. It is ubiquitous in many different modern healthcare and cosmetic products.
But there’s more to this. The amount of PEG in the Moderna and Pfizer vaccines is several orders of magnitude lower than in almost any other PEG-containing healthcare product. PEG laxatives, like those used in over-the-counter stool softeners, have doses in the level of around 20 g. The Pfizer and Moderna vaccines contain around 0.00005g of PEG per dose.
So what does this all mean?
I hate to call out the press, but they’re so focused on COVID-19 (when not covering the recent attempted coup in the USA) and the vaccination that every single event that happens after someone gets the vaccine is blasted across the internet. The stories about Dr. Gregory Michael and Tiffany Dover are among the many examples.
Allergic reactions to PEG is extremely rare, and there have only been a handful of cases of anaphylaxis after receiving these vaccines have been reported. This is out of millions of doses of the vaccines that have been given across the world.
The contraindications from the CDC for the Pfizer and Moderna COVID-19 vaccines were posted in an abundance of caution to help reduce risks to certain individuals. Despite the wild claims of anti-vaxxers, this is how it’s always done with vaccines.
For the vast majority of people, these COVID-19 vaccines are very safe despite these contraindications. And remember, there are at least three new COVID-19 vaccines that will be widely available within a few weeks that should avoid these extremely rare issues. So those who may not be able to receive the mRNA vaccines won’t have to wait long for another vaccine.
- Yang Q, Jacobs TM, McCallen JD, Moore DT, Huckaby JT, Edelstein JN, Lai SK. Analysis of Pre-existing IgG and IgM Antibodies against Polyethylene Glycol (PEG) in the General Population. Anal Chem. 2016 Dec 6;88(23):11804-11812. doi: 10.1021/acs.analchem.6b03437. Epub 2016 Nov 16. PMID: 27804292; PMCID: PMC6512330.