The Second Dose of a COVID-19 Vaccine: Side Effects, Why They Happen, and How to Treat Them

MSK Chief Medical Epidemiologist Mini Kamboj

MSK Chief Medical Epidemiologist Mini Kamboj gets vaccinated.

Both the Pfizer-BioNTech COVID-19 vaccine (Comirnaty®) and Moderna COVID-19 vaccine require two shots, and it’s vital that you get each of them. If you don’t get the second shot, you will not be fully protected from infection. 

The Pfizer-BioNTech vaccine requires two doses given 21 days apart. The Moderna vaccine requires two shots spaced 28 days apart. You must receive the same manufacturer’s vaccine (either Pfizer or Moderna) for your first and second shot and follow the recommended schedule for the second dose. You will make your appointment for the second shot during your appointment for the first shot.

Will I experience side effects from the second dose?

Side effects are more common, and may be more pronounced, after the second dose of the vaccine. Both the Pfizer-BioNTech and Moderna vaccines reported similar side effects, which don’t last long — about one to three days. The most common side effects include a sore arm, fatigue (feeling tired), headache, aches, and fever. Side effects are a good sign — they indicate that the vaccine is working by triggering the immune system. Severe side effects are rare and treatable.

If possible, try to schedule your vaccination prior to your normal day(s) off in case you need some extra rest after the second dose. But remember: You need to follow the recommended schedule for vaccination by getting your second shot at day 21 after the first shot (if you received the Pfizer vaccine) or at day 28 after the first shot (if you received the Moderna vaccine).

A Third Dose of the COVID-19 Vaccine Recommended for Some Cancer Patients With Weakened Immune Systems: Latest Information
As you may have heard, the CDC now recommends a third dose of the COVID-19 vaccine for people who are immunocompromised, including some people with cancer.
Back to top

What do the side effects mean?

If you get side effects, they are a good sign — they indicate that the vaccine is working by triggering the immune system.

When you get the first shot, your immune system recognizes something as being foreign. The immune system automatically launches a small-scale attack against it. This process teaches your immune cells to recognize and respond to an “invader.” That’s why you might experience some side effects.

When you get the second shot, your immune system launches that attack again. But this time, there are more immune cells ready and waiting to launch a much bigger assault. That’s why you might feel more side effects after the second dose. But they will disappear after a day or two.  Think of it this way: The body’s response to the vaccine is like a training mission for the real fight. 

Once you’re fully vaccinated, if you were infected by the virus causing COVID-19, your immune system would be ready to launch an even larger and more powerful attack to protect you.

If you don’t experience any side effects — from either the first or second dose — that doesn’t mean that the vaccine didn’t work. In the vaccine clinical trials, more than half of people didn’t experience any side effects but we still know that the vaccine was effective in those people.

Back to top

Can I treat the side effects?

If you have pain or discomfort after receiving your vaccination, talk to your doctor about taking an over-the-counter medicine, such as ibuprofen (Advil) or acetaminophen (Tylenol).

To reduce pain and discomfort on your arm:

  • Apply a clean, cool, wet washcloth over the area.
  • Use or exercise your arm.

In most cases, discomfort from fever or pain is normal. Contact your doctor or healthcare provider:

  • If the redness or tenderness where you got the shot increases after 24 hours.
  • If your side effects are worrying you or do not seem to be going away after a few days.
Back to top

Can I do anything ahead of time to reduce any side effects from the vaccine?

You should wait until after being vaccinated to see how you feel. If you do experience side effects, it is OK to take an over-the-counter drug (like Advil or Tylenol) to lower a fever, reduce chills, or relieve a headache or body aches. It’s important that you do not take these drugs before getting your vaccine as there are theoretical concerns that some pain relieving drugs may interfere with the immune response to the vaccine. It is also unclear if taking medication ahead of time actually works to reduce post-vaccine symptoms.

Back to top

What if I experience swelling or tenderness away from where I was injected?

Some patients who receive either the Pfizer-BioNTech or Moderna vaccines may experience some swelling or tenderness in their lymph nodes. It is also possible that this swelling will show up on imaging tests and could be mistaken for  progression of  certain cancers — primarily breast, head and neck, melanoma, and lymphoma.

This vaccine side effect is more common after the second dose, usually occurs within two to four days after the vaccination, and can last for an average of 10 days.

On imaging tests, the lymph node enlargement may be detected for a longer period. For these reasons, we recommend:

  • If you develop this symptom after you’re vaccinated, you should speak to your doctor. Most of the time, they will recommend that you wait at least four weeks before getting further tests, to give time for the swelling to disappear.
  • You should schedule your COVID-19 vaccination after any routine imaging. If you’ve already had the vaccine, then we recommend you wait six weeks for any routine breast screenings, including mammography and breast MRI.
  • If you’ve had cancer, you should ask for your COVID-19 vaccine to be administered on the opposite side of your cancer diagnosis if possible.
  • If you have any discomfort from the swelling, you can use a warm compress. Acetaminophen or non-steroidal anti-inflammatory drugs may be taken to ease the discomfort.

It’s important to know that all kinds of vaccines can cause temporary swelling of the lymph nodes, which may be a sign that the body is making antibodies in response as intended.

Back to top

It takes time for the vaccination to provide immunity.

Clinical studies indicate that the vaccination may provide some protection around 12 days after the first dose is given, but you must get both doses in order to achieve full protection. When both doses are administered, the vaccine is more than 90% effective at preventing COVID-19 infection.

On May 13, the CDC stated that people who are fully vaccinated no longer need to wear masks or maintain social distancing in most situations. However, the CDC also noted that people with weakened immune conditions, such as cancer, should talk to their healthcare provider about the need for protective measures even after vaccination. Therefore, to protect our patients from COVID-19, MSK requires that all staff, patients, and visitors must continue to wear masks while at MSK. This requirement includes people who are fully vaccinated.

Back to top

Should I get an antibody test after the vaccine to make sure it’s working?

Antibody testing is not currently recommended check someone’s immunity to COVID-19 following either the Pfizer-BioNTech or Moderna vaccines. The COVID-19 antibody test used at MSK detects the immune response after being infected by COVID-19. It does not measure immunity that results from the vaccine. That’s why it should not be routinely ordered to assess vaccine response.

Back to top

Is it still possible to get COVID-19, even after the second dose? How does the effectiveness compare with vaccines for other diseases?

Both vaccines are among the most effective vaccines in history. They are as effective — if not more — than vaccines for polio, chicken pox, measles and the flu.

The chances of getting sick after vaccination are minimal. Studies show even if you develop COVID-19 after being vaccinated, you are unlikely to get severely ill. Flu vaccines are less effective than the COVID vaccines, but they can protect you from more severe flu illness and hospitalization. The COVID-19 vaccines are even more powerful. Of the more than 30,000 people who received the vaccination during the research trials, only one developed a severe case. The efficacy of the vaccines in the prevention of severe COVID-19 is almost 100%.

Learn more about the COVID-19 vaccines.


May 24, 2021


Additional Resources

Back to top