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Vaccine side effects happen and it all has to do with how an individual person’s immune system works. Vaccine side effects are usually caused by a body’s inflammatory response to a vaccine known as the vaccine’s ‘reactogenicity.’

The reactogenicity of the COVID-19 vaccines, especially, have the potential to produce redness and pain at the site of the injection, some swelling, fatigue, headache, and possibly even fever for some people.

But why do vaccine side effects sometimes make us feel that we have been infected with the very microbe we are supposed to be protected for? The answer is that vaccines are meant to stimulate our immune system with either a whole or partial inactive microbe (or the instructions on how to make part of one). It should not be a surprise that our immune system can sometimes be expected to respond to vaccines in a way that it would be required to help us fight the actual invader.


Vaccination in ArmVaccination in Arm

Many vaccines can result in a sore arm for days. This is quite common and here is what causes it... Minutes after vaccination, our body’s massive cellular defense system, our immune system, starts to become very active with innumerable parts of the system all performing different functions.

Our white blood cells start releasing tons of molecules directly into our bloodstreams in order to engulf the disease-causing microorganisms or the dead cells impersonating them. Some of these released molecules are vasodilators which inflate blood vessels near the site so that more blood cells can come into contact and interact with the ‘invaders.’ Unfortunately, this means there will be redness and swelling at the site.

The pain that may come associated with the redness and swelling is caused by blood cells releasing molecules called cytokines (see cytokine storm below), prostaglandins or ATP (adenosine triphosphate), which directly bind to the pain receptors. (ATP is an organic compound that provides the energy to drive many processes in living cells.) When a certain threshold is met, the body experiences pain.


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These are vaccine side effects that can affect the entire body, known as systemic side effects.

The reason  for this is that some of the molecules released by our blood cells don’t stay at the site of the injection. Since they are present in the blood, some will be swept away and taken to other parts of the body.

One example of an interaction is what can happen with the central nervous system. Higher levels of a chemical called prostaglandin E2 will be produced in the brain by the white blood cells.

The prostaglandin chemical can instruct the brain to constrict blood vessels. This will lead to more heat starting to be produced internally which can produce chills and guide the body to seek sources of heat such as a fever.


Since different vaccines have different reactogenicities, one vaccine may cause more temporary, mild side effects than another. There are several reasons for this:

  • The amount or portion of the virus or partial inactive microbe present in the dose.
  • The presence of an adjuvant, a molecule which is added to the vaccine to enhance the immune response.
  • The type of injection used. For example, injections into the muscle will usually cause fewer side effects than injections into the subcutaneous fat. A slower injection where the needle can move around can also make things worse.
  • The personal characteristics of the person getting vaccinated. There is some evidence that sex hormones and stress can be influential.


We would hope that any side effects following a vaccination are a sign our body will produce enough protective antibodies against the virus, but as of right now, there is little evidence to either prove or disprove this.


COVID-19 VaccineCOVID-19 Vaccine

The COVID-19 vaccines have their own reactogenicity. The data that we do have available (as of July 2021) shows that:

  • For Pfizer and Moderna, about three-quarters of those who get either vaccine reported some sort of pain at the injection site.
  • More reactions, either local or systemic, appeared to come after the second dose compared to the first one.
  • More people have reported side effects from the Moderna than from the Pfizer.
  • Older adults have reported fewer side effect than younger people.


Our body’s immune system has a normal response when an infection is perceived. Part of this response is the release of cytokines, which are biological chemicals that stimulate cell pathways and allow for communication between cells. They are inflammatory proteins. In simple terms, they produce inflammation to attack the invading virus. These cytokines signal the immune system to start doing its job.

The release of cytokines is normally meant to be helpful to us in fighting disease. But, in some individuals, a ‘cytokine storm’ can occur which is akin to an overactive immune system gone wild or into overdrive. The immune system suddenly accelerates the outpouring of these inflammatory cytokine proteins. They flood the bloodstream, leading to increased inflammation throughout the body which can kill tissue and damage organs. A cytokine storm can be fatal to a COVID-19 patient, causing more harm to the individual than the virus itself.

Avoiding a cytokine storm is one very good reason to make sure you get fully vaccinated, even if you experience some unpleasant side effects.

You can be sure that none of the COVID vaccines will give you COVID nor will the flu vaccine give you the flu. The side effects of redness, swelling, fatigue, and fever that can occur are signs that our immune system is on guard for us and are generally normal, unlike what can happen in a cytokine storm to an unfortunate COVID-19 patient with an active infection.


Much more research is needed to determine if side effects such as fatigue and fever after receiving a vaccine means the vaccine will give you sufficient protection against the virus itself. But there is enough evidence that the vaccines appear to be doing their job so far.

The pandemic is not over yet!  It may be wise to continue to wear masks and social distance when in public places.

Please note: Scientific information for this article was sourced with permission from McGill University Office for Science and Society.

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