Side effects appear to be more common after the second dose for both Pfizer-BioNTech and Moderna COVID-19 vaccines.
Both vaccines have received FDA emergency use authorization, and both companies' clinical trials recorded participants experiencing side effects.
But why is the second dose more likely to be tied to more side effects?
How COVID-19 mRNA vaccines work
Both Pfizer and Moderna vaccines are mRNA vaccines, which means they use a copy of a natural chemical — messenger RNA — to produce an immune response. There are spike proteins on the surface of SARS-CoV-2, the virus that causes COVID-19, which help the virus bind to other cells and replicate. mRNA vaccines work to induce an immune response against the spike protein, primarily through antibodies, so when a virus is detected in the future, it can be fought off more swiftly, according to The Atlantic.
Why some individuals experience side effects after receiving the vaccine
Side effects from the vaccine are normal signs the body is building protection against COVID-19, according to the CDC. Sometimes after vaccination, the process of building immunity can cause symptoms, though all side effects should go away within a few days.
Inflammation as an immune response can result in redness, swelling and tenderness at the injection site, along with broader systemic responses, such as fever, headache, muscle aches, joint pain or fatigue, reports Fox's WNYW.
"A number of things happen with regard to inflammation, but it's really a sign that our immune system is recognizing that there's a foreign protein in our body and is preparing to fight it and get rid of it," William Moss, MD, epidemiologist and executive director of the International Vaccine Access Center at Baltimore-based Johns Hopkins University, told WNYW.
The mRNA itself may provoke a reaction from the immune system.
"All of a sudden, you have a lot of new RNA that the cell didn't make," Donna Farber, PhD, an immunologist at New York City-based Columbia University, told The Atlantic.
Why some people experience more severe side effects after the second dose
The Moderna and Pfizer vaccines are administered in two doses, spaced apart by about 28 and 21 days, respectively. More users of V-safe, the CDC's tool to report vaccine side effects, reported side effects within a week of getting their second shot compared to the first, according to a Jan. 27 CDC update.
When hit with the second injection, the immune system is already primed.
"By the second vaccine, it's already amped up and ready to go," Jasmine Marcelin, MD, an infectious disease physician at Omaha-based University of Nebraska Medical Center, told The Atlantic.
Cells that make antibodies need several days to study the spike's features before they can respond. But by the second dose, adaptive cells are faster to react.
"Basically, that second dose is saying, 'Hey, I know a month ago you saw this spike protein. I'm going to remind you once more what it looks like so that you're really ready to attack it,'" Dr. Moss told WNYW.
Why the second COVID-19 dose is important
While there is some protection from a single COVID-19 vaccine dose, protection may be shorter, though it remains unclear. Extending the length of time between doses or skipping the second shot would be "premature and not rooted solidly in the available evidence," the FDA said Jan. 4. The agency emphasized the importance of continuing the two-dose regimen at the studied intervals.
Vaccinated individuals who aren't experiencing any side effects
People shouldn't be concerned by a lack of vaccine side effects, either.
"People who don't have moderate or severe side effects from the vaccine can still have a very protective immune response. They just didn't have, for various reasons, that intense inflammatory response," Dr. Moss told WNYW, citing a combination of genetics and prior history of exposure.