Why are side effects more intense with the second COVID-19 vaccine dose?

You may experience mild to moderate side effects with the COVID-19 vaccine, and if you get a two-dose shot, side effects after the second jab may be more intense than those after the first one.

This is normal and shouldn't deter people from completing their vaccines series, experts say.

In trials of both the Moderna and Pfizer vaccines, more people experienced side effects after the second dose.

"The early advice we gave people who were getting vaccinated was that when you’re getting your second shot, you can tell your employer, 'Hey I’m getting my second shot, it may be that I call in sick,' so then you anticipate it and you're not afraid of it," said Dr. Peter Chin-Hong, an infectious disease expert at UCSF.

About twice as many participants in Pfizer's clinical trial developed chills and joint pain after their second dose than after the initial one. With Moderna, roughly five times as many second-dose recipients experienced chills compared to first-dose recipients. Redness and swelling at the injection site and fevers were also more common with the second dose versus the first for both vaccines.

Dr. Melanie Swift, co-chair of the COVID-19 Vaccine Allocation and Distribution Work Group at the Mayo Clinic, said the side effects are the body developing immunity against the virus.

Swift said with the first dose, your immune system is getting into gear and recognizing the spike protein that the COVID-19 vaccines produce for the first time.

"Your body builds this immune memory," she said. "It’s like your body is going, 'COVID, now I’ve got your number, now I’m ready for you.'"

With the second dose, your body makes the spike protein and releases antibodies.

"Your immune memory cells haven’t forgotten, they’re ready to mount a robust immune response," she said.

Chin-Hong likened the experience of getting a two-dose COVID vaccine to turning on a computer.

"With the first dose, you’re turning on the computer, but then it goes on standby," Chin-Hong explained. "Then with the second shot, it’s immediately activated and it’s ready to fight that invader and it thinks the spike protein is the invader. You get this big boost of the effect, which is a good thing in general, because it’s just means your immune system is working."

It's normal for the body to react to vaccines. With the two-dose Moderna and Pfizer vaccines and the single-dose Johnson & Johnson, the most common reaction among recipients in trials was pain at the injection site. Throughout the rest of your body you may experience tiredness, headache, muscle pain, chills, fever and nausea with all the vaccines.

"Side effects are a good sign," said Swift. "But it confuses people because a lot of these symptoms are COVID symptoms, but the difference is there are no respiratory symptoms as you can get with COVID. With the vaccine, you’re not coughing, you don’t have a runny nose, you don’t lose your sense of taste or smell."

Side effects usually subside on their own after one to two days.

Trials for all the vaccines showed that side effects are more common in women and younger people according to research, said Chin-Hong.