Incorrect vaccine administration is a potential cause of post-vaccine adverse effects, but more research is still needed to confirm or reject this hypothesis

A video published by the Jimmy Dore Show claimed in its title that a study showed COVID-19 vaccines are being administered incorrectly. In the video, the comedian Jimmy Dore cited another video, made by staff nurse John Campbell, who discussed a mouse study, published in the journal Clinical Infectious Diseases, in which researchers detected signs of heart inflammation in mice that received an mRNA COVID-19 vaccine intravenously (into the bloodstream)^[1], rather than intramuscularly (into a muscle), which is the route recommended by vaccine manufacturers Pfizer and Moderna.

Dore’s claim that the study showed COVID-19 vaccines being administered incorrectly is inaccurate. While the study examined what could go wrong in mice if an mRNA COVID-19 vaccine was injected intravenously, it didn’t determine the frequency of incorrect vaccine administration.

That said, vaccine administration technique has come under increasing scrutiny by scientists, following an earlier bioRxiv preprint authored by a research group in Germany, which observed that intravenous administration of an adenovirus-based COVID-19 vaccine (e.g. AstraZeneca-Oxford and Johnson & Johnson) could cause thrombocytopenia (a decrease in platelets in the blood) and blood clots^[2]. The authors of this preprint, as well as those for the Clinical Infectious Diseases study, hypothesized that if incorrect administration was the cause of these adverse effects, then the risk of such effects could be reduced simply by aspirating during vaccination to ensure that the needle isn’t in a blood vessel. Aspiration is performed by pulling back on the syringe’s plunger to ensure that no blood enters the syringe.

Helen Petousis-Harris, a vaccinologist and associate professor at the University of Auckland, told Health Feedback that aspiration was initially practiced to avoid inadvertently injecting the vaccine into the blood when the needle hits a small blood vessel. “But as the flashback of blood hardly ever happens, the practice was abandoned by many practitioners,” she said. [Editor’s note: “Flashback” refers to the initial entry of blood into the syringe; it is a visual indicator that the needle is in a blood vessel.]

Indeed, the U.S. Centers for Disease Control and Prevention currently doesn’t recommend aspiration during vaccination. This newsletter by the Pan American Health Organization, which is the Regional Office for the Americas of the World Health Organization, lists some of the reasons why aspiration during vaccination isn’t recommended, such as minimizing the pain experienced by the vaccine recipient and potential vaccine wastage. Apart from creating unwanted effects, aspiration also isn’t considered necessary because no large blood vessels are present at the anatomical sites involved in intramuscular injection.

More importantly, Petousis-Harris pointed out that “There was no evidence to suggest that the practice [of aspirating] was associated with a greater or lesser rate of injection site reactions.” But she also added that there currently isn’t any evidence to support the rejection of this hypothesis.

It’s important to keep in mind the fact that the exact cause of post-vaccine myocarditis and blood clots in people hasn’t been confirmed yet. Leo Nicolai, a cardiology fellow at the Ludwig Maximilian University of Munich and lead author of the bioRxiv preprint on blood clots, explained that “While these data are interesting and might indicate a simple measure to lower the incidence of vaccine-induced side effects, caution is necessary: all these studies were performed in mice. There is a lack of data on frequency and effects of IV injection in humans.”

Petousis-Harris also observed that while the Clinical Infectious Diseases study “supports the possibility that inadvertent injection into a blood vessel could result in undesirable reactions […] the majority of myocarditis cases are occurring in young males after the second dose, something that this hypothesis does not explain.”

However, certain countries like Denmark now recommend healthcare staff to practice aspiration during COVID-19 vaccination. 

Both Petousis-Harris and Nicolai highlighted that, going forward, it would be helpful to study countries that mandate the practice of aspiration and countries that don’t mandate this practice. If scientists see fewer cases of myocarditis and blood clots in the former compared to the latter, it would be an observation in favor of the hypothesis. If confirmed, it could lead to a widespread change in recommendations about the way COVID-19 vaccines are administered.

Apart from the claim about vaccine administration, Dore commented on ivermectin’s effectiveness against COVID-19, alleging that “the mainstream news does not tell you the truth about [COVID-19], they lied to you about ivermectin, said it was not a human medicine when it won the Nobel Prize for human medicine in 2015”.

While it is true that ivermectin is used in humans and that the scientist who discovered it won a Nobel Prize, what Dore didn’t tell his viewers was that neither of those facts have any bearing on whether ivermectin is effective against COVID-19 specifically. Reliable studies haven’t shown that ivermectin is effective against COVID-19, as explained by Health Feedback here, here, and here.

The fact that scientists won the Nobel Prize for Physiology or Medicine for their discovery of a particular treatment isn’t sufficient grounds for using the treatment for COVID-19. Readers may wish to consider that the scientist who developed the lobotomy also won the same Nobel Prize in 1949. The line of reasoning invoked by Dore here would imply that the lobotomy could also be used to treat COVID-19, yet no one would reasonably propose this operation as a COVID-19 treatment.

It also doesn’t follow that because the drug effectively treats parasitic infections in people that it also works against COVID-19 or that it would be safe for COVID-19 patients. We cannot assume that a drug that is effective for one disease will work for another disease. 

Its safety profile under one condition also doesn’t always mean that the drug will be safe to give to patients with another disease. Many drugs carry contraindications, that is, situations in which they shouldn’t be used. For instance, verapamil, which is a drug used to treat high blood pressure, is dangerous to give to patients suffering from certain heart conditions. Another concern is potential drug interactions between a drug and other drugs that a person is already taking, which could give rise to unwanted effects. This is one reason why physicians recommend patients not to self-medicate.

There are a range of injection techniques for administering vaccines, often with little consensus other than location of injection site. Generally non-live vaccines are given into the muscle. This can be achieved by plunging the needle deep into the muscle tissue and then either:

• Injecting fast and withdrawing the needle
• Injecting slowly before withdrawing
• Pulling back on the plunger, seeing there is no blood, then injecting. This is called aspiration.

The rationale for aspirating is that on very rare occasions, the tip of the needle may be in a tiny blood vessel. The recommendation in that case is to withdraw the needle and start again. The argument was that the vaccine could be inadvertently delivered into the blood rather than the muscle tissue. But as the flashback of blood hardly ever happens, the practice was abandoned by many practitioners. There was no evidence to suggest that the practice was associated with a greater or lesser rate of injection site reactions.

I have not seen any evidence to support the rejection of this hypothesis at this stage. The animal model study supports the possibility that inadvertent injection into a blood vessel could result in undesirable reactions. However, the majority of myocarditis cases are occurring in young males after the second dose, something that this hypothesis does not explain.

My conclusion is that this requires more research and observing the patterns of post-vaccine myocarditis among populations where aspiration is practiced could be helpful.

[Update (19 Oct. 2021): Following the publication of our review, Prof. Petousis-Harris penned a blog post discussing in greater detail the hypothesis of accidental intravenous injection as a cause of post-vaccine adverse effects.]

Indeed, there is peer-reviewed work showing in mice that possibly intravenous injection of mRNA vaccine leads to myocardial inflammation. Our work (under peer review) shows also in mice, that intravenous injection of adenoviral vector based vaccine (AZ1222, ChAdOx1) leads to thrombocytopenia and platelet-directed immune responses, offering a possible explanation for vaccine-induced thrombosis/thrombocytopenia^[2].

While these data are interesting and might indicate a simple measure to lower the incidence of vaccine-induced side effects, caution is necessary: all these studies were performed in mice. There is a lack of data on frequency and effects of IV injection in humans. Most likely, two approaches are needed to further validate the data: large animal studies and studies comparing incidence of vaccine-associated thrombosis/thrombocytopenia/myocarditis in countries with mandated syringe aspiration to countries that don’t mandate this practice.

REFERENCES

• 1 – Li et al. (2021) Intravenous Injection of Coronavirus Disease 2019 (COVID-19) mRNA Vaccine Can Induce Acute Myopericarditis in Mouse Model. Clinical Infectious Diseases.
• 2 – Nicolai et al. (2021) Thrombocytopenia and splenic platelet directed immune responses after intravenous ChAdOx1 nCov-19 administration. bioRxiv. [Note: This is a preprint that hasn’t yet been peer-reviewed.]