Experts Answer Eight Key Questions About Covid-19 Vaccine Reactions

Medical professionals weigh in on why some individuals have different responses to the shots and offer advice on what to expect

Covid-19 Vaccine
After receiving a Covid-19 vaccine, many patients experience side effects, like arm soreness, headache and fever. Angela Weiss / AFP via Getty Images

If you’ve gotten a Covid-19 vaccine already, you may have found yourself comparing your side effects with vaccinated family members and friends or turning to Google to check if the symptoms you’re experiencing are normal.

Now that more than 131 million individuals in the United States have received at least one vaccine dose, and more than 84 million individuals—more than 25 percent of the population—are fully vaccinated, researchers are getting a clearer picture of the potential reactions that can occur after getting a Covid-19 vaccine.

Many recipients experience mild side effects, like arm soreness, fatigue, headache or a low-grade fever, while others may have no side effects at all. Severe side effects, like those that Gregory Poland suffered, are less common. Poland, a physician and vaccinologist at the Mayo Clinic in Rochester, Minnesota, was unlucky enough to come down with uncontrollable shaking and chills for several hours after getting the shot. He’s also one of a small number of individuals who have reported severe ringing in their ear following vaccination. In very rare cases, a half-dozen women have developed severe blot clots after receiving the Johnson & Johnson vaccine.

Although the distribution of the Johnson & Johnson vaccine has been paused out of an abundance of caution, it’s important to know that the vast majority of other vaccine reactions aren’t cause for concern. In fact, it’s perfectly normal that some recipients have stronger reactions than others.

“Vaccine reactions are not evidence of something going wrong, but evidence of something going right,” Poland says.

Why do vaccine reactions happen at all?

Vaccine reactions happen because your immune system is mounting a response to an antigen—a molecule that looks like part of a virus. The antigen used in Covid-19 vaccines is a version of a protein on the SARS-CoV-2 virus. The Moderna and Pfizer vaccines tell your cells to make this protein using a tiny piece of genetic material called mRNA. By contrast, the Johnson & Johnson vaccine uses an engineered virus to shuttle a gene that codes for this protein. Your immune system treats this protein like an invader, Poland explains.

If you’ve never been infected with a virus like SARS-CoV-2, your body doesn’t know how to fight it off. As a result, the virus can slip past your immune system and infect your cells. Vaccines help train your immune system to recognize a pathogen like SARS-CoV-2 so that when it encounters it later, it’s ready to attack it.

Many vaccines require two doses to do this effectively. The first dose of a vaccine introduces the immune system to a specific antigen. This priming shot triggers an initial immune response, and the body starts making antibodies against that antigen.

The Johnson & Johnson vaccine only requires one dose because it elicits a strong immune response. For the Pfizer and Moderna vaccines, this initial immune response isn’t as robust. A second booster shot is needed to kick the immune system in high gear. This immune response is stronger than the first one, and as a result, it often produces worse side effects.

How do the reactions to the different Covid-19 vaccines differ?

Side effects across the Moderna, Pfizer and Johnson & Johnson vaccines are very similar. The two types of side effects you might experience are local and systemic. Local side effects—meaning in the arm where you got the shot—include pain, redness or swelling. Systemic side effects—those that happen throughout the rest of your body—may include tiredness, headache, muscle pain, chills, fever and nausea.

On April 13, federal health officials called for a pause in the use of the Johnson & Johnson vaccine after reports that six women developed a type of blood clot after vaccination. One of the women died, and another is in critical condition. To date, close to seven million individuals in the U.S. have gotten this vaccine. The Centers for Disease Control and Prevention says the blood clots appear to be extremely rare. A CDC advisory panel postponed a decision on the use of Johnson & Johnson’s vaccine until it investigates the cases.

Why do individuals have such different reactions to Covid-19 vaccines?

Put simply: We all have different immune systems. Our immune system is made up of two layers of defense: the innate and adaptive immune systems. The innate immune system is the one we’re born with, meaning it’s heavily influenced by our genetics. Our adaptive immune system, meanwhile, evolves over time. It’s shaped by the pathogens and other substances in the environment that we’re exposed to over the course of our lives.

When you get the first dose of the Covid-19 vaccine, your innate immune system is the first to respond. Some individuals can have stronger reactions to a vaccine because their immune system is just hardwired that way.

“Some people's innate immune system is more reactive to certain stimuli, but not to the extent that it's bad for you,” says Nicholas Pullen, an immunologist and associate professor of biological sciences at the University of Northern Colorado.

Poland is among those whose immune systems overreacted to the vaccine. In doing so, his immune system released more immune signals, or chemicals known as cytokines and chemokines, than the average person. Everyone’s immune system generates different levels of these chemicals based on what our bodies think we need. Some individuals release more of these chemicals than necessary, while other individuals have a more balanced immune response.

The release of the chemicals alerts the adaptive immune system to the threat. Over the next several days to few weeks, the body builds up its adaptive immunity to the pathogen. The second dose of the Pfizer and Moderna vaccines then boosts the adaptive immune system's memory response to the virus.

Are certain groups more likely to have side effects than others?

Younger adults are reporting more side effects from Covid-19 vaccines. Poland says that’s probably because they tend to have more robust immune systems than older adults.

Women also report more side effects than men. It’s possible that men may be more hesitant to speak up about side effects because of cultural expectations of masculinity, but Poland thinks biological reasons exist for this discrepancy.

For one, women tend to have stronger immune responses than men do. Most of the immune response genes are located on the X chromosome. Typically, biologically female individuals are born with two X chromosomes, which means double the number of these genes compared to men.

Women also have thicker fat pads in the deltoid muscle—the part of the upper shoulder where the vaccine is injected. Muscles have a lot of blood vessels, which allow an injected vaccine to be absorbed and carried throughout the body more quickly. But sometimes healthcare workers mistakenly inject the vaccine into the fat instead of the muscle, which can trigger an inflammatory response. Because fat tissue retains injected material for much longer, it’s more susceptible to adverse effects caused by that injection.

What can I do to mitigate side effects before taking the vaccine?

Poland recommends that individuals stay hydrated, eat properly and get enough sleep before their vaccine appointments. “All of those things affect the health of our immune system.”

You should avoid taking pain relievers before your shot because these medications may blunt the body’s immune response to the vaccine. You also shouldn’t get a Covid-19 vaccine at the same time as another vaccine, like the flu or shingles vaccine, according to the CDC.

What can I do to mitigate side effects after taking a vaccine?

Exercising your vaccinated arm, or using a heating pad or ice, can help with soreness and pain. The CDC recommends talking to your doctor about taking over-the-counter medications like ibuprofen, acetaminophen, aspirin or antihistamines for pain or discomfort after getting vaccinated.

You might plan to take time off work after your second dose since symptoms can be worse. Remember to drink plenty of fluids following vaccination.

I didn’t have a reaction to the vaccine. Does that mean it’s not working?

“It's totally a reasonable concern,” Pullen says. “But we have a lot of data now showing that yes, it is effective for people who don't feel those symptoms.”

In the Pfizer vaccine trials, about one out in four reported no side effects. In trials of the Moderna vaccine, side effects were somewhat more common, with 82 percent of individuals experiencing them after the second dose. Despite the range of immune reactions, the Moderna and Pfizer vaccines have shown to be 90 percent effective at preventing Covid-19 in a real-world setting.

If you don’t have any reactions, Pullen says it means your immune system is tuned just right to respond to the vaccine.

How do I know if I’m having an allergic reaction to the vaccine?

“First of all, an allergic reaction to a Covid vaccine is extremely rare,” says Niraj Patel, an allergist and chair of the American College of Allergy, Asthma and Immunology Covid-19 Vaccine Task Force.

But if you do happen to get an allergic reaction after a vaccine, a tell-tale sign is the timing. Whereas normal side effects typically occur four to 48 hours after getting a vaccine, an allergic reaction typically happens within 15 to 30 minutes after administration. That’s why you’re asked to wait for 15 minutes under observation after getting a Covid-19 vaccine.

“An immediate onset is a big clue,” Patel says.

A second clue that you’re experiencing an allergic reaction is the type of symptoms. An allergic reaction is usually sudden and dramatic, involving difficulty breathing or swelling of the lips, tongue or throat. This type of reaction is called anaphylaxis and can be life-threatening.

A small number of recipients have experienced anaphylaxis after receiving the Moderna and Pfizer vaccines. From December 13 to January 13, the CDC reported 4.5 cases of anaphylaxis per million individuals in those who received the mRNA vaccines. A March paper in the Journal of the American Medical Association found that 94 percent of those anaphylaxis cases occurred in women, and most had a history of severe allergic reactions.

While anaphylaxis is certainly scary, Patel says “you're more likely to get struck by lightning than you are to have a severe allergic reaction to the Covid vaccine.” The odds of getting struck by lightning, according to the CDC, are around one in 500,000.

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