What causes COVID-19 vaccine side effects?

The coronavirus vaccines are here, and while some people can't wait to get vaccinated, others are concerned about side effects such as sore arms, fevers and nausea.

But why do the vaccines sometimes cause these unpleasant symptoms, and are they cause for concern? It might seem counterintuitive, but side effects are a sign the vaccine is doing its job, experts told Live Science.

Dr. Susan R. Bailey, an allergist, immunologist and president of the American Medical Association, said side effects develop because your immune system is reacting to the vaccine. People may start to develop fever, fatigue, headache and soreness around the injection area 12 to 24 hours after vaccination. 

Related: Quick guide: COVID-19 vaccines in use and how they work

Here's why: The COVID-19 mRNA vaccines tell the body to make the coronavirus "spike" protein, which the virus uses to enter and infect cells. (The Johnson & Johnson and AstraZeneca vaccines introduce the spike protein via a weakened common cold virus.) The presence of this spike protein initiates an immune response from three types of cells: macrophages, T cells and B cells, said Dr. Nitin Desai, CEO and chief marketing officer of COVID PreCheck, a digital health passport for recent COVID-19 tests and vaccination. Macrophages are the first of these cells to detect and eliminate harmful organisms, while the T cells that migrate to the region where the vaccine was injected help to remember the coronavirus spike protein for future encounters. Once the vaccine is recognized as foreign, B cells  start building up an army of antibodies. 

All of these immune cells produce inflammatory proteins known as cytokines.  Cytokines are chemical messengers that help coordinate the immune response and also trigger  a fever — which is a common side effect of the COVID-19 vaccines. A higher temperature makes the body less hospitable for the virus, and the rise in temperature stimulates the body to create more immune cells. These inflammatory chemicals can also cause muscle pain, fatigue, headaches and other symptoms. But cytokine production plateaus within 24 to 48 hours, which is why most side effects resolve on their own within that time frame, Desai said. 

COVID-19 vaccines introduce just enough spike protein to the immune system to trigger a response. Unlike in severe cases of COVID-19, however, the vaccines do not trigger an out-of-control response known as a cytokine storm, where the body is flooded with the inflammatory chemicals, which then damage organs, Desai said.

Range of side effects 

Because side effects can be a sign of a robust immune system training to detect and destroy the virus, younger people may be more likely to have stronger side effects than the elderly. And, in vaccines that require two shots, such as the Pfizer and Moderna vaccines, side effects may also be worse after the second shot than the first one, because the T-cells remember the previous encounter with the spike protein. Without hesitation, the body quickly unleashes a strong immune response to destroy it — including lots of side-effect-inducing cytokines.

"Consistently, the second shot is showing more side effects but better immune response," Desai told Live Science.

The first dose teaches the immune system to recognize the virus and start producing antibodies and T cells against it, and the second shot is what helps the vaccine reach  the full 94% to 95% efficacy, Desai said.

So, why do people tend to report stronger side effects from the COVID-19 vaccines than from some other vaccines, such as those for the flu? The mRNA COVID-19 vaccines may trigger stronger side effects than the flu shot in part because these vaccines stimulate a stronger immune response, Desai said.

Related: Who should get the Johnson & Johnson vaccine over the mRNA vaccines? 

People who previously recovered from COVID-19 are also likelier to have strong side effects — even after the first shot. That's because their immune systems have already been primed to react to the virus, Bailey said. 

Individual differences, such as stress level and diet, can also influence side effects, Desai said. 

Still, don't fret if you got the shot and had no side effects; the vaccine is still working. 

"Everybody's different in the way that they process vaccines," Bailey told Live Science. "But the clinical studies show that 90% to 95% of patients have a great response to the vaccine whether they have side effects or not."

Rare side effects

Some serious side effects are tied to the vaccine, but they are incredibly rare. 

In very rare instances, people may develop anaphylaxis — a life-threatening but easily treatable allergic reaction — to the COVID-19 vaccines. For example, anaphylaxis occurs in just 2.5 per 1 million shots for the Moderna vaccine, according to a January study in the Centers for Disease Control and Prevention journal Morbidity and Mortality Weekly Report. (The Pfizer shot also induces rare cases of anaphylaxis.) The reaction occurs within 15 minutes of someone getting the vaccine, meaning it is very easy for health care providers to treat it if it does crop up. (For this reason, people who receive the vaccine are asked to remain at the vaccination site for 15 minutes after getting the shot.)

Other serious side effects may or may not be tied to some of the vaccines. Several European countries briefly paused the administration of the AstraZeneca vaccine because of reports of blood clots occurring very rarely. Because the coronavirus itself affects clotting, many experts were suspicious that the side effects were related, Bailey said. 

However, a European Union investigation determined that the vaccine is safe for the general public and found no definitive link to the clots, though the EU regulator could not rule out a connection.

Meanwhile, there are plenty of side effects — ranging from spider bites, to sunburn, to genital herpes — that have been reported to authorities but have absolutely no link to the vaccine, according to data from the U.K. In other words, just because something happens soon after you get the vaccine, that doesn't mean the vaccine caused it. 

Overall, taking your chances with COVID-19 is much riskier than getting a vaccine, Bailey said. 

Given the new coronavirus variants spreading worldwide, it's very important to get vaccinated and be willing to get future booster shots, Desai said.

Bailey agreed. "No one is bulletproof, and we need everybody to get vaccinated so that we can develop herd immunity and protect those in the population who haven't had a chance to get the vaccine yet or who may be in an age group that is not entitled to get the vaccine yet," Bailey said.

Originally published on Live Science.