What does a strong reaction to a COVID-19 vaccine mean?

A doctor explains whether experiencing side effects from the Pfizer, Moderna vaccine signals how well your immune system is working


If someone gets a headache or feels a bit under the weather after receiving a COVID-19 vaccine, it’s become common to hear them say something like “Oh, it just means my immune system is really working hard.” On the flip side, when people don’t notice any side effects, they sometimes worry the shot isn’t doing its job or their immune system isn’t reacting at all.

Is there any link between what you can notice after a vaccine and what’s happening on the cellular level inside your body? Robert Finberg is a physician who specializes in infectious diseases and immunology at the Medical School at the University of Massachusetts. He explains how this perception doesn’t match the reality of how vaccines work.

What does your body do when you get a vaccine?

Your immune system responds to the foreign molecules that make up any vaccine via two different systems.

The initial response is due to what’s called the innate immune response. This system is activated as soon as your cells notice you’ve been exposed to any foreign material, from a splinter to a virus. Its goal is to eliminate the invader. White blood cells called neutrophils and macrophages travel to the intruder and work to destroy it.

This first line of defense is relatively short-lived, lasting hours or days.

The second line of defense takes days to weeks to get up and running. This is the long-lasting adaptive immune responseIt relies on your immune system’s T and B cells that learn to recognize particular invaders, such as a protein from the coronavirus. If the invader is encountered again, months or even years in the future, it’s these immune cells that will recognize the old enemy and start generating the antibodies that will take it down.

In the case of the SARS-CoV-2 vaccines, it takes approximately two weeks to develop the adaptive response that brings long-lasting protection against the virus.

When you get the vaccine shot, what you’re noticing in the first day or two is part of the innate immune response: your body’s inflammatory reaction, aimed at quickly clearing the foreign molecules that breached your body’s perimeter.

What did people report in the week after COVID-19 vaccination?

More than 1.6 million people completed post-vaccination surveys in the U.S. between Dec. 14, 2020 and Jan. 13, 2021 as part of the Centers for Disease Control’s V-safe program. About 70% of respondents reported pain at the spot where they received the Moderna or Pfizer
injection. In the first week after receiving the vaccine, the most common systemic side effect reported was fatigue.0%25%50%75%100%Injection site pain70.9%Fatigue33.5%Headache29.5%Muscle pain22.9%Chills11.6%Fever11.4%Injections site swelling10.8%Joint pain10.4%Nausea8.9%Chart: The Conversation, CC-BY-ND Source: Gee J, Marquez P, Su J, et al. First Month of COVID-19 Vaccine Safety Monitoring — United States, December 14, 2020–January 13, 2021. MMWR Morb Mortal Wkly Rep 2021;70:283–.Get the data

It varies from person to person, but how dramatic the initial response is does not necessarily relate to the long-term response. In the case of the two mRNA COVID-19 vaccines, well over 90% of people immunized developed the protective adaptive immune response while fewer than 50% developed any side effects, and most were mild.

You may never know how strongly your body’s adaptive immune response is gearing up.

The bottom line is you can’t gauge how well the vaccine is working within your body based on what you can detect from the outside. Different people do mount stronger or weaker immune responses to a vaccine, but post-shot side effects won’t tell you which you are. It’s the second, adaptive immune response that helps your body gain vaccine immunity, not the inflammatory response that triggers those early aches and pains.

What are side effects anyway?

Side effects are normal responses to the injection of a foreign substance. They include things like fever, muscle pain and discomfort at the injection site, and are mediated by the innate immune response.

Neutrophils or macrophages in your body notice the vaccine molecules and produce cytokines – molecular signals that cause fever, chills, fatigue and muscle pain. Doctors expect this cytokine reaction to happen any time a foreign substance is injected into the body.

Researchers anticipate some reports of side effects. Adverse events, on the other hand, are things that physicians do not expect to happen as a result of the vaccine. They would include organ failure or serious damage to any part of the body.

The blood clots that triggered the U.S. to pause distribution of the Johnson & Johnson vaccine  JNJ, +2.72% are a very rare event, apparently happening with one-in-a-million frequency. Whether they are definitely caused by the vaccine is still under investigation – but if scientists conclude they are, blood clots would be an extremely rare side effect.