Safety Considerations for COVID-19 Vaccines

Safety considerations for COVID-19 vaccines

In clinical trials of COVID-19 vaccines, post-vaccination reactions were generally similar. While the frequency of some reactions varied by age, vaccine manufacturer, and vaccine dose, commonly reported reactions follow below.

• Local reactions included pain/tenderness, and, less commonly, swelling and redness at the injection site, and localized axillary or groin adenopathy on the same side as the vaccinated arm or thigh.
• Systemic reactions included fever, fatigue/malaise, headache, chills, myalgia, arthralgia, and diarrhea; among younger children, particularly those younger than age 3 years, systemic reactions also included irritability/crying, sleepiness, and loss of appetite.

In all age groups, most symptoms were mild to moderate in severity, typically began 1–3 days after vaccination, and resolved after 1–3 days.

Package inserts can be consulted for detailed information about post-vaccination reactions.

Febrile seizures in infants and young children occur infrequently after any vaccination. One febrile seizure was reported among participants ages 6 months–23 months in Moderna's COVID-19 vaccine clinical trial; febrile seizures have been reported during postmarketing use of the vaccine. The potential impact of simultaneous administration of COVID-19 and routine vaccines on the risk of febrile seizures has not been specifically studied. CDC is continuing to monitor for febrile seizures following COVID-19 vaccination in infants and young children.

COVID-19 vaccination and myocarditis and pericarditis

Considerations for COVID-19 vaccination

Cases of myocarditis and pericarditis have rarely been observed following receipt of COVID-19 vaccines used in the United States. Cases have occurred most frequently in adolescent and young adult males within 7 days after receiving the second dose of an mRNA COVID-19 vaccine (Moderna and Pfizer-BioNTech); however, cases have also been observed in females and after other doses. Data also suggest an increased risk of myocarditis and pericarditis following Novavax vaccination.

Vaccine recipients, especially males ages 12–39 years, should be made aware of the rare risk of myocarditis and pericarditis following receipt of these vaccines, and the benefit of COVID-19 vaccination in reducing the risk of severe outcomes from COVID-19, including the possibility of cardiac sequelae.

• Counseling should include the need to seek care if symptoms of myocarditis or pericarditis, such as chest pain, shortness of breath, or palpitations develop after vaccination, particularly in the week after vaccination.

• In younger children, symptoms of myocarditis might also include non-specific symptoms such as irritability, vomiting, poor feeding, tachypnea, or lethargy.

• Extending the interval between the first and second doses to 8 weeks (i.e., extended interval) might reduce the rare risk of vaccine-associated myocarditis and pericarditis. The extended interval consideration applies only to children ages 6–23 months who are not moderately or severely immunocompromised and receive a multidose initial series (Table 1)

For additional information on COVID-19 vaccine and myocarditis or pericarditis, see the June 2025 ACIP presentation and the vaccine package inserts.

For people who have a history of myocarditis associated with multisystem inflammatory syndrome in children (MIS-C) or multisystem inflammatory syndrome in adults (MIS-A), see COVID-19 vaccination and MIS-C and MIS-A.

Myocarditis or pericarditis within 3 weeks after a dose of COVID-19 vaccine

Development of myocarditis or pericarditis within 3 weeks after a dose of any COVID-19 vaccine is a precaution to a subsequent dose of any COVID-19 vaccine, and subsequent doses should generally be avoided. Experts advise that these people should:

• Generally not receive a subsequent dose of any COVID-19 vaccine
• If, after a risk assessment, the decision is made to administer a subsequent COVID-19 vaccine dose, wait until at least their episode of myocarditis or pericarditis has resolved and there is no evidence of ongoing heart inflammation or sequelae.

• Considerations for subsequent COVID-19 vaccination might include:
  • Myocarditis or pericarditis considered unrelated to vaccination (e.g., due to SARS-CoV-2 or other viruses)
  • Personal risk of severe COVID-19 (e.g., age, underlying medical conditions)
  • Timing of any immunomodulatory therapies; General Best Practices for Immunization can be consulted for more information

Myocarditis or pericarditis before COVID-19 vaccination or more than 3 weeks after a COVID-19 vaccine dose

People who have a history of myocarditis or pericarditis that occurred before COVID-19 vaccination or more than 3 weeks after a COVID-19 vaccine dose may receive any current Food and Drug Administration (FDA)-approved vaccine after the episode of myocarditis or pericarditis has completely resolved and there is no evidence of ongoing heart inflammation or sequelae. This includes people who had myocarditis or pericarditis due to SARS-CoV-2 or other viruses.

History of other heart disease

People who have a history of other heart disease, including congenital heart disease and Kawasaki disease, may receive any currently FDA-approved COVID-19 vaccine.

Reporting vaccine adverse events

VAERS

For all licensed COVID-19 vaccines (Moderna [mNexspike, Spikevax], Novavax, Pfizer-BioNTech) healthcare providers are strongly encouraged to report to the Vaccine Adverse Event Reporting System (VAERS) the following:

• Any adverse event that occurs after the administration of a vaccine licensed in the United States, whether or not it is clear that a vaccine caused the adverse event
• Vaccine administration errors, whether or not associated with an adverse event

Information on how to submit a report to VAERS is available at https://vaers.hhs.gov or by calling 1-800-822-7967.

V-safe

V-safe is an active surveillance system to rapidly monitor for reactogenicity and health events after COVID-19 vaccination. Vaccine recipients can register to participate in V-safe through the V-safe website.