A: The most common side effects of the Moderna and Pfizer vaccines–the two closest to FDA approval–include sore arm, muscle aches, fatigue, and headache. These side effects are signs that your immune system is working.
This post will focus on the Moderna and Pfizer vaccines because they are the furthest along in development, have safety data and are likely both to be available before the end of the year. It is important to note that these two vaccines are relatively similar because they are both mRNA vaccines (to be discussed later), The other vaccines in development use different ways of activating the immune system. The side effects and their incidence will be different for the other vaccines and we do not know entirely what they are yet since they are still in clinical trials.
Both the Moderna and Pfizer vaccines are mRNA vaccines. mRNA (also called messenger RNA–note this is not DNA!) is a molecular message that tells your cells at the site of the injection to temporarily make a small snippet part of the SARS-Cov2 virus: the spike protein. The spike protein is the part that the virus uses to enter your cells to make copies of itself. By stimulating the immune system against the spike protein, the goal is to stop the actual virus from being able to enter your cells. None of the vaccines in development contain SARS-CoV-2. Instead they are all focused on the spike protein using different technologies.
The mRNA tells the muscle cells in the area where you are injected to temporarily make the spike protein. Some of your other immune cells–T cells and B cells- may recognize the spike protein through a receptor on their surface. These cells will start to get excited that they recognize something and divide to make copies of themselves. The immune cells also make signals called cytokines that tell other cells “something foreign is here, get armed and ready”. Some of your T cells–the helper T cells–help the B cells make antibodies. B cells usually have an antibody stuck to it on their surface. The T cell helps the B cell change so that it turns into an antibody producing machine. The B cells will then make a lot of antibodies and secrete them into your bloodstream.
All this immune activity–the immune cells proliferating, changing into antibody producing machines, and producing cytokines–results in a local reaction. Most of this action can happen at the injection site and within a nearby lymph node. Most vaccines that we have had cause local reactions, such as sore arm, redness, and swelling. When the cytokines are expressed at higher levels, they can get into the bloodstream and result in fever, fatigue, and muscle aches. These are temporary and subside as the levels of cytokines go down.
The vaccine is a two injection series. The first injection is more likely to cause only a local reaction. The first injection results in some T and B cell proliferation and antibody production. The second injection causes your immune cells to proliferate more, since there are more T and B cells that recognize the spike protein from being activated on the first dose. It also results in higher levels of antibodies that are protective.
Importantly, second injections or “booster shots” usually result in what is known as “immunological memory”, meaning that the T and B cells live longer–potentially many years. The second injection is thus more likely to get a bigger immune reaction and result in temporary fevers, fatigue, headache or muscle aches as the immune system is more activated by this injection and more cytokines are being secreted into the bloodstream. These side effects are all signs from your immune system being tricked into thinking that the spike protein from the vaccine is a foreign invader. As the spike protein goes away, so do the side effects. But your immune system remembers.
The immunity is built and remains for if/when we encounter SARS-CoV2.
The Moderna vaccine had 15,000 people receive the vaccine in their study, while the Pfizer vaccine had over 20,000 people receive the vaccine. It is possible that there are more rare side effects that did not happen to occur in those (combined) 35,000 people. They might emerge once the vaccine rolls out to a larger population, but at this time it is not known.
All in all, the side effects from the Moderna vaccine and the Pfizer vaccine are mostly localized with the first injection and are more likely to cause fever, muscle aches, headache and fatigue with the second injection.
High fevers occured in less than 2% in participants in both the Moderna and the Pfizer trials. In Moderna, the side effects that were disruptive were fatigue (9.7%), muscle pain (8.9%), joint pain (5.2%), and headache (4.5%). In Pfizer’s vaccine trial, the side effects that were disruptive to daily life were fatigue (3.8%) and headache (2%) in the second vaccine. These side effects are temporary.
While inconvenient, the side effects are a good sign of the immune system doing its job of preparing itself for being invaded by something more sinister–SARS-CoV-2. This second injection is what results in high enough levels of antibodies to prevent and/or reduce infection, and is designed to result in longer-lived immunological memory. This nerdy girl can’t wait to line up to get hers! I might try to plan the second injection on a Friday so I can rest up on Friday night and Saturday….very exciting weekend plans!
Press release on side effects: