Safety Considerations for COVID-19 Vaccines

Safety considerations for COVID-19 vaccines

In clinical trials of different COVID-19 vaccine types, post-vaccination reactions were generally similar.

Common, Mild-to-Moderate Side Effects (Short-Term)

While the frequency and severity of some reactions varied by age, vaccine manufacturer, and vaccine dose, commonly reported reactions included:

• 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. Further research and post-marketing studies are underway to better understand the short-, mid- and long-term side effects and adverse events ranging from mild to severe.

Serious Adverse Events (Confirmed Causal or Strong Signal)

CDC's monitoring systems (VAERS, VSD, V-safe, CISA) and international bodies have identified the following as confirmed or strongly suspected serious adverse events:

• Anaphylaxis: severe allergic reaction

• Myocarditis/pericarditis: heart muscle/lining inflammation

• Thrombosis with Thrombocytopenia Syndrome (TTS): blood clots with low platelets

• Guillain-Barré Syndrome (GBS): disorder in which the body's immune system damages nerves

• Cerebral venous sinus thrombosis (CVST): large, potentially fatal blood clot in the brain

• Febrile seizures: convulsion in a young child that is triggered by a sudden spike in body temperature or a high fever

Febrile seizures in infants and young children occur infrequently after any vaccination; febrile seizures have been reported during postmarketing use of COVID-19 vaccines. 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.

Package inserts should be consulted for detailed information regarding risks, adverse events, and post-vaccination reactions.

Potential Safety Signals: Adverse Events of Special Interest (AESI) Monitored by CDC

CDC's active surveillance aims to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination. An AESI for COVID-19 is a pre-identified, medically significant condition monitored closely during vaccine safety surveillance, even if a causal link is not yet proven. Conditions being monitored by CDC to determine if there is an association or causality between vaccination and specific clinical outcomes includes:

Cardiovascular / blood-related: Acute myocardial infarction; Myocarditis; Pericarditis; Deep vein thrombosis; Pulmonary embolism; Thrombosis with thrombocytopenia syndrome (TTS); Thrombotic thrombocytopenic purpura; Thrombocytopenia; Hemorrhagic stroke; Ischemic stroke; Cerebral venous sinus thrombosis

Neurological: Guillain-Barré syndrome (GBS); Bell's palsy; Encephalitis; Encephalopathy; Acute disseminated encephalomyelitis; Transverse myelitis; Chronic inflammatory demyelinating polyneuropathy; Multiple sclerosis; Narcolepsy; Cataplexy; Trigeminal neuralgia and related disorders; Meningitis

Allergic/immunologic: Anaphylaxis

Reproductive/pregnancy-related: Gestational diabetes; Postmenopausal bleeding; Stillbirth; Perinatal death; Major birth defects

Other systemic: Acute respiratory distress syndrome (ARDS); Vaccine-associated enhanced disease; Non-COVID mortality; ICU admission; Local injection-site reactions; Administration errors

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. Clinical 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. Note that giving more than one dose of COVID-19 vaccine to persons 2 years of age and older is off-label use.

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), anyone can report an adverse event to Vaccine Adverse Event Reporting System (VAERS) and healthcare professionals are required to report certain adverse events that come to their attention. Healthcare professionals are strongly encouraged to report to 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.