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I Felt Sick After Getting a Vaccine. Why?

Pain, redness, even fever after getting vaccinated can be explained by how the immune system works

Many years ago, I received the flu shot for the very first time and, later that day, I began to feel sick. Fatigue, body temperature on the rise and a general unease made me think I actually had the flu. “Why get a flu shot if it’s going to give you the flu?” I thought at the time and skipped that shot for a few years before being convinced to get it again.

It turns out that my reaction to the flu shot was natural. It did not give me the flu. Rather, it was probably inflammation created by my body in response to the vaccine, and this inflammatory response is known as a vaccine’s “reactogenicity.” The COVID-19 vaccines bring with them their own baggage of reactogenicity: potential redness and pain at the site of the injection, a bit of swelling, and sometimes body-wide symptoms like fatigue, headache and even fever.

So what exactly is going on inside the body that makes us think we’ve been infected by a nasty bug when it’s just a vaccine?

An activated ecosystem

A vaccine stimulates our immune system by presenting an inactive microbe, either whole or partial (or even the instructions to make part of one), to our body. It’s no wonder then that our immune system sometimes responds to this by triggering the same cascade of events that is required to help us fight the real deal.

Many of the vaccines I have received have resulted in a sore arm for a few days. An injection site symptom like this is quite common. What causes it? Within minutes of being vaccinated, a branch of our immune system starts becoming very active. The immune system is a universe unto itself, an ecosystem of different cell types and chemical messages. Its complexity is legendary among those who study it. A great article published in The Atlantic last year put it thusly: “immunology is where intuition goes to die.” That’s not to say that immunologists throw their hands up in the air when asked to explain what is going on with our body’s cellular defence system. Rather, our immune system is a little bit like those massive battle sequences in The Lord of the Rings movies: impressive in scope and involving innumerable agents all performing different functions.

After getting vaccinated, some of our white blood cells—namely mast cells and macrophages—start releasing heaps of molecules into our bloodstream. Mast cells got their name because they were originally believed to help feed the biological tissue around them, and mast is German for “fattening”; macrophages are literally “large eaters” that can invaginate themselves to engulf disease-causing microorganisms or dead cells.

Some of the molecules they release post-vaccination are vasodilators, which inflate local blood vessels. It means that more blood cells can come and interact with the injected solution, but it also means redness and swelling. The pain itself at the site of injection can be caused by blood cells releasing certain molecules like cytokines, prostaglandins or ATP and directly binding to pain receptors. When a threshold is met, like hitting a funfair’s strength tester strong enough to trigger the bell, you experience pain.

Some of a vaccine’s side effects are systemic: they affect the entire body. This is because some of the molecules unleashed by our blood cells don’t stay at the site of injection. They are, after all, present in the blood, so some are swept away and taken to other parts of the body. For example, they can interact with our central nervous system, which leads to higher levels of prostaglandin E2 in the brain. This prostaglandin can instruct the brain to constrict blood vessels, to start producing more heat internally, to give us chills, and to guide us to seek sources of heat: essentially, a fever.

“No pain, no gain”?

Before we blame all of these side effects on vaccines themselves, it is important to point out that two things happening in close proximity does not automatically imply that one caused the other. In the 1980s, a team at a children’s hospital in Finland wanted to figure out if the side effects reported after receiving the measles-mumps-rubella vaccine were really all caused by the vaccine itself. They recruited 581 pairs of twins (aged 14 months to 6 years) that were to be vaccinated and cleverly divided up each pair: one twin got the actual vaccine and, three weeks later, a placebo shot (identical in composition to the vaccine but without the bits from viruses), while the other twin got the placebo first, followed by the vaccine. Neither the twins nor the medical staff knew which was which, and side effects were documented.

It turned out that many of the side effects reported had nothing to do with the viral bits themselves. In fact, reports of nausea, vomiting and respiratory symptoms were more common following injection with the placebo than with the real deal. The authors speculated that increased parental observation following vaccination and the common presence of infections in children probably accounted for the reporting of side effects when all the child got was a placebo.

But vaccines can cause side effects. Different vaccines have different reactogenicities, meaning vaccine A may cause more of these temporary, mild or moderate side effects than vaccine B, and there are reasons for that. The amount of virus present in the dose can influence reactogenicity, as can the presence of an adjuvant, a molecule added to enhance immune response. The type of injection used also plays a part, with injections into the muscle (very common for vaccines) usually causing fewer side effects than injections into the subcutaneous fat. A slower injection, during which the needle can move around and cause more transient damage, can make things worse. And then there are the personal characteristics of the person getting vaccinated: there is evidence that sex hormones and stress can influence reactogenicity.

Are these side effects a good thing? Some believe that side effects following vaccination are really a sign that our body will produce enough protective antibodies against the virus, but as a 2019 review on the subject concludes, we do not yet know if this is true. The idea itself, commonly referred to as “no pain, no gain,” is certainly tempting: you get vaccinated, and if you feel like you got hit by a car, it means you’ll be fine when faced with the actual virus. There is, however, limited data to either prove or disprove the “no pain, no gain” theory. Side effects after vaccination, when they are indeed caused by the vaccine, mean that part of our immune system is reacting to the vaccine, but it may not automatically imply that we will be adequately protected when the virus comes along. At the risk of sounding clichéd, more research is needed.

The COVID-19 vaccines have their own reactogenicity, which was assessed in the clinical trials that put these vaccines through their paces. We now have some real-world data on both Pfizer’s and Moderna’s, published a few days ago in the Journal of the American Medical Association. The numbers are in keeping with what was reported for the trials themselves, with an average of 70-75% of people reporting some sort of injection site reaction, usually pain. More reactions, either local or systemic, were reported after the second dose compared to the first one, and more people reported side effects when they received the Moderna vaccine compared to Pfizer’s. Meanwhile, older adults reported fewer side effects than younger people.

The COVID vaccines will not give you COVID, just like the flu vaccine does not transmit the flu. The redness, fatigue and fever that can accompany vaccination are signs that our immune system, intricate and marvellous, is on guard for us.

Take-home message:
- Swelling and redness in the place where you were injected with a vaccine can be explained by molecules being secreted by blood cells. These molecules cause blood vessels to dilate and thus more blood cells can flow in the area
- A fever after vaccination can be due to chemicals secreted by white blood cells making their way to the brain and leading to higher levels of a molecule called prostaglandin E2, which instructs the body to raise its temperature and to give us chills
- There is too little data to know if getting side effects like fatigue and fever after receiving a vaccine means that the vaccine is doing its job and you will gain sufficient protection against the virus itself


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