Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States

Purpose

The Centers for Disease Control and Prevention (CDC) Interim Clinical Considerations provides additional information to healthcare professionals and public health officials on the use of COVID-19 vaccines. They are informed by the Advisory Committee on Immunization Practices (ACIP) and CDC’s recommendations, data submitted to the U.S. Food and Drug Administration (FDA) for Biologics License Application (BLA) or Emergency Use Authorization (EUA) of the vaccines, other data sources including the World Health Organization (WHO)-emergency use listing (EUL) evaluation of COVID-19 vaccines and clinical trial results, general best practice guidelines for immunization, and expert opinion. These considerations apply only to the use of vaccine products currently approved or authorized in the United States. These considerations will be updated when additional information becomes available or if additional vaccine products are approved or authorized.

In addition to the following considerations, the BLA or EUA conditions of use and storage, handling, and administration procedures described in the prescribing information should be referenced when using the Pfizer-BioNTechexternal icon, Modernaexternal icon, and Janssenexternal icon COVID-19 vaccines.

Overview of COVID-19 vaccine recommendations

COVID-19 vaccines approved or authorized by the Food and Drug Administration 

Three COVID-19 vaccines are currently approved under a BLA or authorized under an EUA by FDA:

• Pfizer-BioNTech COVID-19 vaccine (COMIRNATY)¹
• Moderna COVID-19 vaccine
• Janssen (Johnson & Johnson) COVID-19 vaccine

COVID-19 vaccine recommendations   

COVID-19 vaccination is recommended for all people aged 12 years and older in the United States for the prevention of COVID-19. However, the age groups approved under BLA or authorized under EUA to receive vaccination vary by vaccine product. CDC has issued recommendations for primary series, additional, and booster doses of COVID-19 vaccines.

The following groups are recommended to receive COVID-19 vaccine:

Primary series

• Pfizer-BioNTech: a 2-dose primary series in persons aged ≥12 years
• Moderna: a 2-dose primary series in persons aged ≥18 years
• Janssen: a single dose primary series in persons aged ≥18 years

Additional dose for moderately and severely immunocompromised people after completion of an mRNA primary series*

• Pfizer-BioNTech: persons aged ≥12 years
• Moderna: persons aged ≥18 years

After completion of an mRNA primary series and an additional mRNA vaccine dose, moderately and severely immunocompromised people are eligible for a booster dose as described below.

* Recommendations for moderately to severely immunocompromised people who received a single dose Janssen COVID-19 primary series are included in the booster dose section below.

Booster dose

Any of the COVID-19 vaccines can be used for booster vaccination, regardless of the vaccine product used for primary vaccination. When a heterologous or “mix and match” booster dose is administered, the eligible population and dosing intervals are those of the vaccine used for primary vaccination.

mRNA COVID-19 vaccine (Pfizer-BioNTech, Moderna) recipients

The following recipients of an mRNA primary series should receive a single COVID-19 booster dose (Pfizer-BioNTech, Moderna or Janssen) at least 6 months after completion of the primary series:

• People aged 65 years and older
• Residents aged 18 years and older in long term care settingsexternal icon
• People aged 50–64 years with certain underlying medical conditions

The following recipients of an mRNA primary series may receive a single COVID-19 booster dose (Pfizer-BioNTech, Moderna or Janssen) at least 6 months after completing their primary series based on their individual benefits and risks:

• People aged 18–49 years with certain underlying medical conditions
• People aged 18–64 years at increased risk for SARS-CoV-2 exposure and transmission because of occupational or institutional setting

Janssen COVID-19 vaccine recipients

• People aged ≥18 years who received a single dose Janssen primary series should receive a single COVID-19 booster dose (Pfizer-BioNTech, Moderna or Janssen) at least 2 months (8 weeks) after completing their Janssen primary series.

These additional dose and booster dose recommendations also apply to people who received two doses of different mRNA COVID-19 vaccine products for their primary series.

Moderately to severely immunocompromised people aged ≥18 years who received a 2-dose mRNA primary series and an additional mRNA additional dose (3 total mRNA vaccine doses) are eligible for a single COVID-19 booster dose (Pfizer-BioNTech, Moderna or Janssen) at least 6 months after completing their third mRNA vaccine dose.

There is currently no FDA-approved or FDA-authorized COVID-19 vaccine for children aged <12 years. Ongoing clinical trials of COVID-19 vaccine in children <12 years are examining a range of vaccine doses that are lower than the standard dose prescribed for people ≥12 years. Data from these trials will be used to determine the optimal dose to protect children aged <12 years while minimizing potential adverse events. Children aged <12 years should not receive any COVID-19 vaccine doses (either standard or partial doses) at this time.

COVID-19 vaccine dosing and schedule

Dosing

Primary series

COVID-19 vaccines are administered intramuscularly as either a two-dose series or single dose.

Vaccine manufacturer	Primary dose	Primary dose volume	Number doses/series	Interval between primary doses	Interval between primary and booster doses
Pfizer-BioNTech	30 µg	0.3 ml	2	3 weeks (21 days)	≥ 6 months
Moderna	100 µg	0.5 ml	2	1 month (28 days)	≥ 6 months
Janssen	5×1010 viral particles	0.5 ml	1	Not Applicable	≥ 2 months

COVID-19 vaccines are administered intramuscularly. A single COVID-19 vaccine primary series (i.e., either a 2-dose mRNA COVID-19 vaccine series or a single dose of Janssen COVID-19 vaccine) should be administered. People are not recommended to receive more than one complete COVID-19 primary series, with the exception of recipients of a hematopoietic cell transplant (HCT) or chimeric antigen receptor (CAR)-T-cell therapy.

A person is considered fully vaccinated against COVID-19 ≥2 weeks after receipt of the second dose in a 2-dose series (Pfizer-BioNTech and Moderna) or ≥2 weeks after receipt of the single dose of the Janssen vaccine. CDC has developed interim public health recommendations for fully vaccinated people . Administration of an or a booster dose is not required to be considered fully vaccinated for public health purposes. People who have a contraindication to vaccination or who otherwise do not complete a primary vaccination series are not considered fully vaccinated. People who have received an additional dose or a booster dose should continue to follow guidance for fully vaccinated persons to minimize spread of SARS-CoV-2 to others at this time.

Additional dose

• Pfizer-BioNTech: 30 ug in a volume of 0.3 ml (same as the primary series and booster doses)
• Moderna: 100 µg in a volume of 0.5 ml (same as the primary series doses)

Booster dose

The booster dose and volume are the same regardless of whether the dose is homologous (same as primary series) or heterologous (different than primary series).

Booster dose

Vaccine manufacturer	Booster dose	Booster volume
Pfizer-BioNTech	30 µg	0.3 ml
Moderna	50 µg	0.25 ml
Janssen	5×1010 viral particles	0.5 ml

• Pfizer-BioNTech: 30 ug in a volume of 0.3 ml (same as the primary series and additional doses)
• Moderna: 50 µg in a volume of 0.25 ml. This is half the amount used for the primary series and additional dose.
• Janssen: 5×10¹⁰ viral particles in a volume of 0.5ml (same as the primary series doses).

Intervals between vaccine dose²

Primary series

Individuals who receive the second dose of an mRNA COVID-19 vaccine no more than 4 days before (referred to as the “grace period”) or at any time after the recommended second dose date are considered to have completed the primary series.³ If the second dose of a vaccine is given earlier than the 4-day grace period (i.e., the second dose is administered <17 days [Pfizer-BioNTech] or <24 days [Moderna]), the second dose should be repeated. The repeat dose should be spaced after the dose given in error by the recommended minimum interval (see Appendix A for more details).

Additional dose

The additional dose (i.e., third dose) of an mRNA COVID-19 vaccine should be administered at least 28 days after completion of the initial 2-dose mRNA COVID-19 primary (see Considerations for COVID-19 vaccination in moderately and severely immunocompromised people).³ If the additional dose of an mRNA COVID-19 vaccine is given fewer than 24 days after the second dose (i.e., administered earlier than the 4-day grace period), the additional dose should be repeated. The repeat dose should be spaced after the dose given in error by the recommended minimum interval (see Appendix A for more details).

Booster dose

If a heterologous vaccine product is used for the booster dose, the interval should follow the interval recommended by the primary series; e.g., people who received a single dose Janssen primary series can receive an mRNA COVID-19 vaccine booster dose at least 2 months (8 weeks) after completing their Janssen primary series. In people eligible to receive an mRNA or Janssen COVID-19 booster dose, if the booster dose is given earlier than the recommended interval (i.e., <6 months after a second mRNA primary vaccine dose and <2 months [<8 weeks] after a Janssen primary vaccine dose), the booster dose does not need to be repeated.

Vaccine administration errors and deviations

Information on preventing, reporting, and managing COVID-19 vaccine administration errors is found in Appendix A. Vaccine administration errors should be reported to the Vaccine Adverse Event Reporting System (VAERS)external icon.

Interchangeability of COVID-19 vaccine products

Any currently FDA-approved or FDA-authorized COVID-19 vaccine can be used when indicated; ACIP and CDC do not state a product preference. In general, primary series and additional doses should be with the same vaccine product. However, use of heterologous booster doses as discussed below is authorized.

mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna): primary series and additional doses

All doses of the primary series and the additional dose (for moderately and severely immunocompromised people, if indicated, should be completed with the same product. Various strategies  can help ensure that people receive the appropriate product and interval between doses.

In exceptional situations in which the mRNA vaccine product given for the first dose of the primary series cannot be determined or is not available, any available mRNA COVID-19 vaccine may be administered at a minimum interval of 28 days between doses to complete the mRNA COVID-19 vaccination series. In situations where the same mRNA vaccine product is temporarily unavailable, it is preferable to delay the second dose to receive the same product than to receive a mixed primary series using a different product. If two doses of different mRNA COVID-19 vaccine products are administered in these situations (or administered inadvertently), the primary series is considered complete and no subsequent doses of either product are recommended to complete the primary series. Such persons are considered fully vaccinated against COVID-19 ≥2 weeks after receipt of the second dose of an mRNA vaccine and may be offered an additional dose or booster dose

Janssen vaccine: primary series

In limited, exceptional situations where an individual received the first dose of an mRNA COVID-19 vaccine but is unable to complete the series with either the same or different mRNA COVID-19 vaccine (e.g., due to contraindication), a single dose of Janssen COVID-19 vaccine may be considered at a minimum interval of 28 days from the mRNA COVID-19 vaccine dose. See the Contraindications and Precautions section for additional information on use of Janssen COVID-19 vaccine and additional precautions in people with a contraindication to mRNA COVID-19 vaccines. People who receive Janssen COVID-19 vaccine after a dose of an mRNA COVID-19 vaccine should be considered to have received a valid, single-dose Janssen vaccination—not a mixed primary vaccination series—and are considered fully vaccinated against COVID-19 ≥2 weeks after receipt of the single dose of the Janssen vaccine.

Interchangeability of booster doses

Heterologous (mix and match) booster doses can be used (see Considerations for use of a COVID-19 vaccine booster dose for more details).

People vaccinated for prevention of COVID-19 outside the United States

People who were vaccinated outside the United States with a currently FDA-approved or FDA-authorized COVID-19 vaccine or a WHO-EUL COVID-19 vaccine⁴ and who have received all the recommended doses are considered fully vaccinated and do not need any subsequent primary series doses.

People who received the first dose of a 2-dose FDA-approved or FDA-authorized mRNA COVID-19 vaccine do not need to restart the vaccine series in the United States. They should receive the second dose as close to the recommended time as possible and upon completion of the 2-dose primary series are considered fully vaccinated.

People who completed a primary vaccine series outside the United States and received FDA-approved, FDA-authorized, or WHO-EUL⁴ COVID-19 vaccines as a mixed dose regimen are considered fully vaccinated as per CDC guidance. They do not need to restart a COVID-19 vaccine primary series in the United States. This does not imply that these non-U.S. vaccine primary series regimens are approved or authorized by FDA or are recommended by CDC or ACIP.

The following people who received a COVID-19 vaccine that is not currently FDA-approved or FDA-authorized in the United States may be offered a complete FDA-approved or FDA-authorized COVID-19 vaccine primary series as follows:

• People who have received only the first dose of a 2-dose COVID-19 primary series listed for emergency use by WHO⁴
• People who received all or some of the recommended doses of a COVID-19 vaccine primary series that is not listed for emergency use by WHO.

The minimum interval between receipt of the non-FDA-approved/authorized vaccine and initiation of the FDA-approved/authorized COVID-19 vaccine primary series is at least 28 days.

People vaccinated outside the United States: administration of a COVID-19 vaccine booster dose or additional dose

People who were vaccinated outside the United States and completed a primary vaccination series comprised of an FDA-authorized or FDA-approved COVID-19 vaccine (i.e., a single dose Janssen vaccine or a 2-dose mRNA vaccine [including a mixed mRNA primary series]) may receive a booster dose (Pfizer-BioNTech, Moderna or Janssen) if they are eligible. Considerations for use of a COVID-19 booster dose can be consulted for more information.

People who have completed a 2-dose mRNA COVID-19 vaccine (including a mixed mRNA primary series) may receive an additional mRNA dose (Pfizer-BioNTech or Moderna) at least 28 days after receiving the second mRNA vaccine dose if they are moderately or severely immunocompromised. Considerations for COVID-19 vaccination in moderately and severely immunocompromised people can be consulted for more information.

People vaccinated for prevention of COVID-19 as part of a clinical trial in the United States

Some people in the United States have completed a COVID-19 vaccination series as part of a clinical trial with sites in the United States involving a COVID-19 vaccine that is currently neither approved nor authorized by FDA.

People who participated in a clinical trial in the United States and received the full series of a COVID-19 vaccine that is neither approved nor authorized by FDA but is listed for emergency use by WHO⁴

Clinical trial participants from U.S. sites who received all recommended doses of a COVID-19 vaccine that is neither approved nor authorized for use by FDA but is listed for emergency use by WHO do not need any additional doses of an FDA-approved or FDA-authorized COVID-19 vaccine. Once it has been confirmed that a U.S. participant in a COVID-19 vaccine trial received “active” vaccine, and not placebo, the participant can be considered fully vaccinated 2 weeks after they completed the vaccine series. Currently, the AstraZeneca COVID-19 vaccine meets these criteria.

People who participated in a clinical trial in the United States and received the full series of a COVID-19 vaccine candidate that is neither approved nor authorized by FDA nor listed for emergency use by WHO⁴

If a clinical trial participant from a U.S. site has been documented to have received the full series of an “active” (not placebo) COVID-19 vaccine candidate, and vaccine efficacy has been independently confirmed (e.g., by a data and safety monitoring board), the participant can be considered fully vaccinated 2 weeks after they completed the vaccine series. Currently, the Novavax COVID-19 vaccine meets these criteria. This does not imply that the vaccine has been approved or authorized by FDA or is recommended by CDC or ACIP.

Novavax clinical trial participants who did not receive the full 2-dose series of the active COVID-19 vaccine candidate should follow current prevention measures to protect themselves against COVID-19 and be offered an FDA-approved or FDA-authorized COVID-19 vaccine series.

Coadministration of COVID-19 vaccines with other vaccines

Studies to assess the safety and immunogenicity of coadministration of COVID-19 vaccines with other vaccines are underway or in development. As detailed in general best practices, extensive research on the simultaneous administration of the most widely used live and inactivated vaccines has demonstrated seroconversion rates and rates for adverse reactions similar to those observed when the vaccines are administered separately.

COVID-19 vaccines may be administered without regard to timing of other vaccines. This includes simultaneous administration of COVID-19 vaccine and other vaccines on the same day. It is not known if the reactogenicity of COVID-19 vaccines is increased with coadministration, including with other vaccines known to be more reactogenic, such as adjuvanted vaccines. When deciding whether to administer an(other) vaccine(s) with a COVID-19 vaccine, vaccination providers should consider whether the patient is behind or at risk of becoming behind on recommended vaccines, their risk of vaccine-preventable disease (e.g., during an outbreak or occupational exposures), and the reactogenicity profile of the vaccines.

If multiple vaccines are administered at a single visit, administer each injection in a different injection site. For adolescents and adults, the deltoid muscle can be used for more than one intramuscular injection administered at different sites in the muscle.

Best practices for multiple injections include:

• Label each syringe with the name and the dosage (amount) of the vaccine, lot number, the initials of the preparer, and the exact beyond-use time, if applicable.
• Separate injection sites by 1 inch or more, if possible.
• Administer the COVID-19 vaccines and vaccines that may be more likely to cause a local reaction in different limbs, if possible.

COVID-19 vaccination and SARS-CoV-2 infection

People with prior or current SARS-CoV-2 infection

COVID-19 vaccination is recommended for everyone aged 12 years and older, regardless of a history of symptomatic or asymptomatic SARS-CoV-2 infection; this includes people with prolonged post-COVID-19 symptoms and applies to primary series, additional doses, and booster doses. Viral testing to assess for acute SARS-CoV-2 infection or serologic testing to assess for prior infection is not recommended for the purpose of vaccine decision-making.

Data from clinical trials indicate that the currently approved or authorized COVID-19 vaccines can be given safely to people with evidence of a prior SARS-CoV-2 infection. Among individuals infected with SARS-CoV-2, substantial heterogeneity exists in their immune response. Conversely, the immune response following COVID-19 vaccination is reliable, consistent, and predictable. A primary vaccination series decreases the risk of future infections in people with prior SARS-CoV-2 infection. Numerous immunologic studies have consistently shown that vaccination of individuals who were previously infected enhances their immune response, and growing epidemiologic evidence indicates that vaccination following infection further reduces the risk of subsequent infection, including in the setting of increased circulation of more infectious variants.

People with known current SARS-CoV-2 infection should defer vaccination at least until the person has recovered from the acute illness (if the person had symptoms) and they have met criteria to discontinue isolation. Current evidence about the optimal timing between SARS-CoV-2 infection and vaccination is insufficient to inform guidance. This recommendation for vaccination applies to people who experience SARS-CoV-2 infection before receiving any vaccine dose and those who experience SARS-CoV-2 infection after the first dose of a COVID-19 vaccine but before receipt of subsequent doses.

People with a history of multisystem inflammatory syndrome in children (MIS-C) or adults (MIS-A)

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition in children and adolescents infected with SARS-CoV-2. Multisystem inflammatory syndrome in adults (MIS-A) appears to be even rarer and is less well characterized than in children. The mechanisms of MIS-C and MIS-A are not well understood but include a dysregulated immune response to SARS-CoV-2 infection. The risk of recurrence of the same dysregulated immune response following reinfection with SARS-CoV-2 among people with a history of MIS-C or MIS-A is unknown. It is also unknown if some persons with a history of MIS-C or MIS-A may be at risk for an MIS-like illness following vaccination with COVID-19 vaccine.

Current evidence suggests that the risk of SARS-CoV-2 reinfection is low after initial infection but may increase with time due to waning immunity. Children with MIS-C have high antibody titers to SARS-CoV-2external icon  however, it is unknown if this correlates with protection against reinfection and for how long protective antibody levels persist.

Given the lack of data on the safety of COVID-19 vaccines in people with a history of MIS-C or MIS-A, a conversation between the patient, their guardian(s), and their clinical team or a specialist is strongly encouraged to assist with decisions about the use of COVID-19 vaccines.

Given the widespread transmission of SARS-CoV-2 across the United States and increases in hospitalizations of children and adolescents, several experts consider the benefits of COVID-19 vaccination for children and adolescents (i.e., a reduced risk of severe disease including potential recurrence of MIS-C after reinfection) to outweigh a theoretical risk of an MIS-like illness or the known risks of COVID-19 vaccination such as the rare risk of myocarditispdf icon following COVID-19 vaccination for people who meet the following criteria:

1. Clinical recovery has been achieved, including return to normal cardiac function;
2. It has been ≥90 days since their diagnosis of MIS-C;
3. They are in an area of high or substantial community transmission of SARS-CoV-2, or otherwise have an increased risk for SARS-CoV-2 exposure and transmission; and
4. Onset of MIS-C occurred before any COVID-19 vaccination.

COVID-19 vaccination may also be considered for people with a history of MIS-C who do not meet all the above criteria or for people with a history of MIS-A. Experts view clinical recovery, including return to normal cardiac function, as an important factor when considering COVID-19 vaccination. Additional factors when considering individual benefits and risks may include:

1. An increased personal risk of severe COVID-19 (e.g., age, underlying conditions)
2. Timing of immunomodulatory therapies (ACIP’s general best practice guidelines for immunization can be consulted for more information)

People diagnosed with MIS-C or MIS-A after COVID-19 vaccination

In the rare instance of a person developing MIS-C, MIS-A or a similar clinical illness after receipt of a COVID-19 vaccine, referral to a specialist in infectious diseases, rheumatology, or cardiology should be considered. Because MIS-C and MIS-A are conditions known to occur with SARS-CoV-2 infection, these individuals should be assessed for laboratory evidence of current or prior SARS-CoV-2 infection. Healthcare and public health professionals should also consider requesting a consultation from the Clinical Immunization Safety Assessment COVIDvax project. In addition, all illnesses consistent with MIS-C or MIS-A occurring in persons who received any COVID-19 vaccine should be reported to VAERSexternal icon.

People who received passive antibody products

Currently, there are no data on the safety and effectiveness of COVID-19 vaccines in people who received monoclonal antibodies or convalescent plasma as part of COVID-19 treatment. Based on the estimated half-life of such therapies and evidence suggesting that reinfection is uncommon within the 90 days after initial infection, vaccination should be deferred for at least 90 days after receiving monoclonal antibodies or convalescent plasma for treatment. This is a precautionary measure until additional information becomes available, to avoid potential interference of the antibody therapy with vaccine-induced immune responses. This recommendation applies to people who receive passive antibody therapy before receiving any vaccine dose and between doses. Receipt of passive antibody therapy in the past 90 days is not a contraindication to receipt of COVID-19 vaccine. COVID-19 vaccine doses received within 90 days after receipt of passive antibody therapy do not need to be repeated.

For people receiving antibody therapies not specific to COVID-19 treatment (e.g., intravenous immunoglobulin, RhoGAM), administration of COVID-19 vaccines either simultaneously with or at any interval before or after receipt of an antibody-containing product is unlikely to substantially impair development of a protective antibody response. Thus, there is no recommended minimum interval between antibody therapies not specific to COVID-19 treatment and COVID-19 vaccination. Similarly, there is no recommended minimum interval between receipt of anti-SARS-CoV-2 monoclonal antibodies or convalescent plasma and vaccines for non-COVID-19 diseases. Vaccines other than COVID-19 vaccines, including inactivated and live vaccines, may be administered without regard to timing of anti-SARS-CoV-2 monoclonal antibodies.

Vaccinated people who subsequently develop COVID-19

COVID-19 treatment-specific clinical guidelines⁵ should be consulted when making treatment decisions (including use of anti-SARS-CoV-2 monoclonal antibodies, convalescent plasma, antiviral treatment, or corticosteroid administration) for people who have previously received one or more doses of COVID-19 vaccine and subsequently develop COVID-19.

For purposes of surveillance, infections in fully vaccinated people (i.e., breakthrough infections) are defined as detection of SARS-CoV-2 RNA or antigen in a respiratory specimen collected ≥14 days after completion of all recommended doses of a currently FDA-approved or FDA-authorized COVID-19 vaccine. Infections in fully vaccinated people that result in hospitalization or death should be reported to VAERSexternal icon.

Antiviral therapy and COVID-19 vaccination

Administration of an antiviral drug at any interval before or after vaccination with any of the currently FDA-approved or FDA-authorized COVID-19 vaccines, including the adenovirus vector Janssen COVID-19 vaccine, is unlikely to impair development of a protective antibody response.

Vaccinating people with a known COVID-19 exposure or during COVID-19 outbreaks

COVID-19 vaccines are not currently recommended for outbreak management or for post-exposure prophylaxis to prevent SARS-CoV-2 infection in a person with a known exposure. Because the median incubation period of COVID-19 is 4–5 days, it is unlikely that a dose of COVID-19 vaccine would provide an adequate immune response within the incubation period for effective post-exposure prophylaxis.

Unvaccinated people in the community or in outpatient settings who have had a known COVID-19 exposure should not seek vaccination until their quarantine period has ended to avoid potentially exposing healthcare personnel and others during the vaccination visit. This also avoids causing diagnostic confusion between possible adverse effects of vaccination and symptoms of a new COVID-19 diagnosis. This recommendation also applies to people with a known COVID-19 exposure before receipt of the primary series, an additional dose, or booster dose.

Residents or patients with a known COVID-19 exposure or undergoing screening in congregate healthcare settings (e.g., long-term care facilities and other long-term care settingsexternal icon) or congregate non-healthcare settings (e.g., correctional and detention facilities, homeless shelters) may be vaccinated. In these settings, exposure to and transmission of SARS-CoV-2 can occur repeatedly for long periods of time, and healthcare personnel and other staff are already in close contact with residents. People residing in congregate settings (healthcare and non-healthcare) who have had an exposure and are awaiting SARS-CoV-2 testing results may be vaccinated if they do not have symptoms consistent with COVID-19. Vaccination providers should employ appropriate infection prevention and control procedures.

Vaccinating people receiving medical care unrelated to COVID-19

Provision of medical care in an inpatient or outpatient setting (e.g., outpatient clinic, urgent care center, emergency department) can serve as an opportunity to offer COVID-19 vaccination to people who are unvaccinated or who are eligible to receive a second, additional, or booster dose of vaccine. Clinicians should discuss the importance of completing the recommended vaccination schedule with their patients who are unvaccinated, partially vaccinated, or whose vaccination status is unknown at the time of a clinical encounter. Considerations for administering COVID-19 vaccine include:

• Absence of symptoms consistent with COVID-19 or known current SARS-CoV-2 infection
• Absence of known close contact with someone with confirmed COVID-19
• Testing for SARS-CoV-2 not being done for diagnostic purposes
• Absence of a moderate or severe acute illness with or without a fever, to avoid diagnostic confusion between manifestations of the underlying illness and possible adverse effects of vaccination

Additional recommendations from ACIP’s general best practices for immunization may be considered.

Vaccinating people undergoing SARS-CoV-2 screening

Unvaccinated people who are being screened for SARS-CoV-2 infection (e.g., work or school requirement, prior to travel) may be candidates for same-day vaccination if they 1) are asymptomatic; 2) do not have a recent known or suspected exposure to SARS-CoV-2; and 3) receive a negative test result.

Considerations for COVID-19 vaccination in moderately and severely immunocompromised people

People with immunocompromising conditions or people who take immunosuppressive medications or therapies are at increased risk for severe COVID-19. The currently FDA-approved or FDA-authorized COVID-19 vaccines are not live vaccines and therefore can be safely administered to immunocompromised people. However, reduced vaccine effectiveness has been observed in immunocompromised participants compared to participants who are not immunocompromised in a limited number of studies. Small studiespdf icon have demonstrated that an additional mRNA COVID-19 vaccine dose in some immunocompromised people who received an mRNA COVID-19 primary vaccine series may enhance antibody response, increasing the proportion of people who respond.

Considerations for use of an additional dose of mRNA COVID-19 vaccine in moderately and severely immunocompromised people after an initial 2-dose mRNA COVID-19 vaccine series

For public health purposes, immunocompromised people who have completed a primary vaccine series (i.e., 2-dose mRNA vaccine series [Pfizer-BioNTech and Moderna] or a single dose of Janssen vaccine) are considered fully vaccinated ≥2 weeks after completion of the series. However, an additional dose of an mRNA COVID-19 vaccine after an initial 2-dose mRNA COVID-19 primary vaccine series should be considered for people with moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments. These conditions and treatments include but are not limited to:

• Active treatment for solid tumor and hematologic malignancies
• Receipt of solid-organ transplant and taking immunosuppressive therapy
• Receipt of CAR-T-cell therapy or HCT (within 2 years of transplantation or taking immunosuppression therapy)
• Moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome)
• Advanced or untreated HIV infection (people with HIV and CD4 cell counts <200/mm³, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV)
• Active treatment with high-dose corticosteroids (i.e., ≥20 mg prednisone or equivalent per day when administered for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory.

Factors to consider in assessing the general level of immune competence in a patient include disease severity, duration, clinical stability, complications, comorbidities, and any potentially immune-suppressing treatment. Age or place of residence alone (e.g., residence in a long-term care settingexternal icon, independent of a patient’s medical condition, should not be used to determine the level of immune competence, as the balance of benefits and risks of an additional dose for people who are not moderately to severely immunocompromised is currently unknown.

Additional information about the level of immune suppression associated with a range of medical conditions and treatments can be found in general best practices for vaccination of people with altered immunocompetence, the CDC Yellow Book, and the Infectious Diseases Society of America policy statement, 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Hostexternal icon.

Whenever possible, mRNA COVID-19 vaccination doses (including the primary series, additional dose, and booster dose) or the single dose Janssen COVID-19 vaccine (primary or booster) should be completed at least two weeks before initiation or resumption of immunosuppressive therapies. Timing of COVID-19 vaccination should take into consideration current or planned immunosuppressive therapies and optimization of both the patient’s medical condition and response to vaccine. A patient’s clinical team is best positioned to determine the degree of immune compromise and appropriate timing of vaccination.

The utility of serologic testingexternal icon or cellular immune testing to assess immune response to vaccination and guide clinical care (e.g., as part of need assessment for an additional dose) has not been established. Serologic testing or cellular immune testing outside of the context of research studies is not recommended at this time.

The additional mRNA COVID-19 dose should be the same vaccine product as the initial 2-dose mRNA COVID-19 primary series (Pfizer-BioNTech or Moderna). If the mRNA COVID-19 vaccine product given for the first two doses is not available, the other mRNA COVID-19 vaccine product may be administered. If a mixed mRNA vaccine primary series was administered (one dose of Pfizer-BioNTech and one dose of Moderna), the person may still receive an additional mRNA dose at least 28 days after the second dose.

Until additional data are available, the additional dose of an mRNA COVID-19 vaccine should be administered at least 28 days after completion of the initial 2-dose mRNA COVID-19 primary vaccine series, based on expert opinion.³

Consult Considerations for use of a COVID-19 booster dose for guidance on the use of booster doses in people who are moderately and severely immunocompromised.

Considerations for COVID-19 revaccination

HCT and CAR-T-cell recipients who received doses of COVID-19 vaccine prior to receiving an HCT or CAR-T-cell therapy should be revaccinated with a primary vaccine series at least 3 months (12 weeks) after transplant or CAR-T-cell therapy.

An additional dose of an mRNA COVID-19 vaccine (if revaccinated with a 2-dose mRNA COVID-19 vaccine primary series) is recommended as part of revaccination for persons who continue to have moderate to severe immune compromise. Based on expert opinion and until additional data are available, the additional dose of an mRNA COVID-19 vaccine can be administered at least 28 days after receipt of the second dose. A patient’s clinical team is best positioned to determine the degree of immune compromise and appropriate timing of vaccination.

Reinforcement of the need for prevention measures among immunocompromised people

People who are immunocompromised (including people who receive an additional mRNA COVID-19 vaccine dose after an initial 2-dose mRNA COVID-19 primary vaccine series) should be counseled about the potential for a reduced immune response to COVID-19 vaccines and the need to continue to follow current prevention measures (including wearing a mask, staying 6 feet apart from others they don’t live with, and avoiding crowds and poorly ventilated indoor spaces) to protect themselves against COVID-19 until advised otherwise by their healthcare professional. Close contacts of immunocompromised people should also be strongly encouraged to be vaccinated against COVID-19 to protect these people.

Considerations for use of a COVID-19 vaccine booster dose

Recommendations for use of a single COVID-19 booster dose after completion of a primary series can be found in the Overview of COVID-19 vaccine recommendations. CDC recommends that people who received an mRNA primary series and are aged ≥65 years, residents aged ≥18 years in long-term care settings, or aged 50-64 years with certain underlying medical conditions should receive a single COVID-19 vaccine booster ≥6 months after completion of their primary mRNA vaccine series. People aged ≥18 years who received a Janssen primary series should also receive a single COVID-19 vaccine booster ≥2 months after their Janssen primary dose.

Individual benefit-risk assessment considerations for receiving a booster dose

CDC recommends that people aged 18-49 years with certain medical conditions, including pregnancy, and people aged 18-64 years and at increased risk for SARS-CoV-2 exposure and transmission because of occupational or institutional setting may receive an mRNA COVID-19 booster dose based on their individual benefits and risks.

The benefits of a COVID-19 booster dose may include a reduced risk of SARS-CoV-2 infection and a reduced risk for severe COVID-19. Receiving a booster dose may prevent morbidity (including post-COVID symptoms) and may reduce transmission of the virus to other people. People in this risk category should consider the following risk factors for SARS-CoV-2 infection and the potential impact of SARS-CoV-2 infection:

• Risk of exposure to SARS-CoV-2. Factors that would be expected to affect the risk of exposure to SARS-CoV-2 include work or residence in certain settings; level of community transmission; rates of COVID-19 vaccination in their community; and the likelihood of frequent interactions with possibly unvaccinated people from outside an individual’s household, and adherence to current prevention measures.
• Risk for developing SARS-CoV-2 infection. A person’s risk for developing SARS-CoV-2 infection may vary based on time from completing a primary COVID-19 vaccine series and time from prior SARS-CoV-2 infection due to waning immunity.  Serologic testing or cellular immune testing is not recommended as part of the individual risk benefit assessment.
• Risk for severe infection related to underlying conditions. A person’s risk of developing severe COVID-19 may vary by the type, number, and level of control of specific medical conditions as well as other yet to be defined variables. People may receive a COVID-19 vaccine booster. Separately, also see section on Considerations for COVID-19 vaccination in moderately and severely immunocompromised people.
• Potential impact of SARS-CoV-2 infection. SARS-CoV-2 infections that are not severe may still lead to morbidity (e.g., post-COVID-19 symptoms). A person’s individual circumstances should also be considered; these may include living with/caring for a person who is medically frail or immunocompromised or a child who is not eligible for COVID-19 vaccine or the inability to work or meet other personal obligations when infected, even if not severely ill with COVID-19.

Individual benefit-risk considerations for selecting which booster dose to receive

For groups recommended to receive a booster, people have the option to receive any of the FDA-approved or FDA-authorized COVID-19 booster products (Pfizer-BioNTech, Moderna [half dose] or Janssen). People may consider the benefits and risks of each product and discuss with their healthcare provider which product is most appropriate for them.

Clinical trial data show that homologous COVID-19 booster doses (utilizing the same vaccine product for the primary series and booster dose) increase the immune response against SARS-CoV-2 and have an acceptable safety profile for all FDA-approved or FDA-authorized COVID-19 vaccine boosters (Pfizer-BioNTechpdf icon, Modernapdf icon [half dose] or Janssenpdf icon).

One studypdf icon of heterologous (mix-and-match) booster dosing showed that all three of the FDA-approved or FDA-authorized vaccine boosters doses led to a strong serologic response in groups primed by all three vaccines. For a given COVID-19 primary vaccine series, heterologous boosters elicited similar or higher serologic responses as compared to their respective homologous booster responses.

People may also discuss with their healthcare provider the risks of different FDA-approved or FDA-authorized vaccines. The frequency and type of transient local and systemic symptoms after a booster dose is generally similar to those experienced after a primary series. Anaphylaxis is a rare risk, but the rate of anaphylaxis after a booster dose is not yet known.

Potential risks of an mRNA COVID-19 booster dose include the rare risks of myocarditis and pericarditispdf icon. Based on data after mRNA COVID-19 primary series, the group at the highest risk for myocarditis and pericarditis are males aged <30 years. Additional considerations are available for people with a history of myocarditis or pericarditis.

Potential risks of a Janssen COVID-19 booster include the rare risks of  thrombosis with thrombocytopenia syndrome (TTS) and Guillain-Barré Syndrome (GBS). Based on data after receipt of a Janssen COVID-19 primary dose, the group at the highest risk for GBS are males aged 50-64 years and the group highest at risk for TTS are women aged 18-49 years. Women aged 18-49 years should be made aware of the increased risk for TTS and the availability of mRNA COVID-19 vaccines for use as a booster dose.  People who developed TTS after their initial Janssen vaccine should not receive a Janssen booster dose. Considerations for use of the Janssen COVID-19 vaccine in certain populations can be consulted for additional information.

People who are moderately and severely immunocompromised and COVID-19 vaccine booster dose 

Moderately and severely immunocompromised people aged ≥18 years who completed an mRNA COVID-19 vaccine primary series and received an additional mRNA vaccine dose may receive a single COVID-19 booster dose (Pfizer-BioNTech, Moderna or Janssen) at least 6 months after completing their third mRNA vaccine dose. In such situations, people who are moderately and severely immunocompromised may receive a total of four COVID-19 vaccine doses. A person who is moderately or severely immunocompromised and has received two doses of an mRNA vaccine and “≥28 days has elapsed since the second dose, should receive an additional mRNA dose immediately (if Moderna COVID-19 vaccine is used, administer 100µg in 0.5ml), followed ≥6 months later by a single COVID-19 vaccine booster dose (if Moderna vaccine booster is used, administer 50µg in 0.25ml).

Moderately and severely immunocompromised people aged ≥18 years who received a single dose Janssen COVID-19 vaccine primary series should receive a single COVID-19 booster vaccine (Pfizer-BioNTech, Moderna or Janssen) at least 2 months (8 weeks) after receiving their initial Janssen primary dose. If the Moderna vaccine is used in this circumstance, the booster dose and dose volume should be used (50µg in 0.25ml). A patient’s clinical team is best positioned to determine the appropriate timing of vaccination. A person who received one primary dose of Janssen COVID-19 vaccine should not receive more than two COVID-19 vaccine doses as detailed in Appendix A.

Considerations for vaccination of people with certain underlying medical conditions

Any currently FDA-approved or FDA-authorized COVID-19 vaccine can be administered to people with underlying medical conditions who have no contraindications to vaccination; ACIP and CDC do not state a product preference. Clinical trials demonstrated similar safety and efficacy profiles in people with some underlying medical conditions, including those that place them at increased risk for severe COVID-19 symptoms, compared to people without comorbidities. Additional information for people with specific underlying medical conditions is included below. Healthcare professionals or health departments in the United States can request a consultation from the Clinical Immunization Safety Assessment COVIDvax project if they have complex COVID-19 vaccine safety questions not readily addressed by CDC guidance.

People with a history of myocarditis or pericarditis

Myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the lining around the heart) have occurred rarely in some people following receipt of mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna). The mechanisms that cause myocarditis or pericarditis following vaccination with an mRNA COVID-19 vaccine are not well understood. Cases of myocarditis or pericarditis have occurred predominantly in males aged 12-29 years within a few days after receiving the second dose of vaccine. Most patients have been hospitalized for short periods, with the majority achieving resolution of acute symptoms. Follow-up is ongoing to identify and understand potential long-term outcomes among cases.

There are limited data on the safety and efficacy of COVID-19 vaccines in people with a history of myocarditis or pericarditis. The interim considerations for the clinical scenarios detailed as follows may be updated as new information is obtained.

Myocarditis or pericarditis after receipt of a dose of an mRNA COVID-19 vaccine but before administration of a subsequent dose

It is unclear if people who developed myocarditis or pericarditis after a dose of an mRNA COVID-19 vaccine may be at increased risk of further adverse cardiac effects following a subsequent dose of the vaccine. Until additional safety data are available, experts recommend that people who develop myocarditis or pericarditis after a dose of an mRNA COVID-19 vaccine defer receiving a subsequent dose.

Administration of a subsequent dose of an mRNA COVID-19 vaccine can be considered in certain circumstances for people who develop myocarditis or pericarditis after receiving a dose of an mRNA COVID-19 vaccine. Considerations for vaccination may include:

• Personal risk of severe acute COVID-19 (e.g., age, underlying conditions)
• Level of COVID-19 community transmission and personal risk of infection
• Additional data on the risk of myocarditis or pericarditis following an occurrence of either condition after a dose of an mRNA COVID-19 vaccine
• Additional data on the long-term outcomes of myocarditis or pericarditis that occurred after receipt of an mRNA COVID-19 vaccine
• Timing of any immunomodulatory therapies; ACIP’s general best practice guidelines for immunization can be consulted for more information

People who choose to receive a subsequent dose of an mRNA COVID-19 vaccine should wait at least until their episode of myocarditis or pericarditis has completely resolved. This includes resolution of symptoms attributed to myocarditis or pericarditis, as well as no evidence of ongoing heart inflammation or sequelae as determined by the person’s clinical team, which may include a cardiologist, and special testing to assess cardiac recovery. Decisions about proceeding with a subsequent dose should include a conversation between the patient, their parent, guardian, or caregiver (when relevant), and their clinical team.

Clinicians should consult current clinical guidance for information on the evaluation and management of myocarditis.

History of myocarditis or pericarditis prior to COVID-19 vaccination

People who have a history of myocarditis or pericarditis unrelated to mRNA COVID-19 vaccination (e.g., due to SARS-CoV-2 or other viruses) may receive any currently FDA-approved or FDA-authorized COVID-19 vaccine after the episode of myocarditis or pericarditis has completely resolved. This includes resolution of symptoms attributed to myocarditis or pericarditis, as well as no evidence of ongoing heart inflammation or sequelae as determined by the person’s clinical team, which may include a cardiologist, and special testing to assess cardiac recovery. Considerations for COVID-19 vaccination in people with a history of MIS-C or MIS-A are discussed here.

CDC is continuing to investigate cases of myocarditis or pericarditis after mRNA COVID-19 vaccination; this guidance may be updated as new information is obtained. All cases of myocarditis or pericarditis following COVID-19 vaccination should be reported to VAERSexternal icon.

People with autoimmune conditions

People with autoimmune conditions were enrolled in COVID-19 vaccine clinical trials. Safety and efficacy of vaccines in this population were similar to the general population. People with autoimmune conditions may receive any currently FDA-approved or FDA-authorized COVID-19 vaccine. If people with these conditions are immunocompromised because of medications such as high-dose corticosteroids or biologic agents, they should follow the considerations for immunocompromised people.

People with autoimmune conditions were enrolled in COVID-19 vaccine clinical trials. Safety and efficacy of vaccines in this population were similar to the general population. People with autoimmune conditions may receive any currently FDA-approved or FDA-authorized COVID-19 vaccine. If people with these conditions are immunocompromised because of medications such as high-dose corticosteroids or biologic agents, they should follow the considerations for immunocompromised people.

People with a history of Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is a neurological disorder in which the body’s immune system damages nerve cells, causing muscle weakness and sometimes paralysis. ACIP’s general best practices for immunization do not include a history of GBS as a contraindication to vaccination; a history of GBS is a precaution for influenza vaccines and tetanus-toxoid containing vaccines in limited situations.⁶ Reports of adverse events following use of the Janssen COVID-19 vaccine under EUA suggest an increased risk of GBSexternal icon during the 42 days following vaccination. The highest risk has been observed in males aged 50-64 years. No increased risk of GBS has been identified with mRNA vaccines during use under EUA.

People with a history of GBS can receive any currently FDA-approved or FDA-authorized COVID-19 vaccine. However, given the possible association between the Janssen COVID-19 vaccine and an increased risk of GBS, a patient with a history of GBS and their clinical team should discuss the availability of mRNA COVID-19 vaccines to offer protection against COVID-19.

Any occurrence of GBS following COVID-19 vaccination should be reported to VAERSexternal icon. CDC and FDA will continue to monitor and review cases of GBS among people who receive any currently FDA-approved or FDA-authorized COVID-19 vaccine in the United States and may update this guidance in the future.

People with a history of Bell’s palsy

Cases of Bell’s palsy (acute peripheral facial nerve palsy) were reported following vaccination of participants in the COVID-19 vaccine clinical trials. Available data were insufficient for FDA to conclude that these cases were causally related to vaccination. Post-authorization safety surveillance will be important to further assess any possible causal association. In the absence of such evidence, people with a history of Bell’s palsy may receive any currently FDA-approved or FDA-authorized COVID-19 vaccine. Any occurrence of Bell’s palsy following COVID-19 vaccination should be reported to VAERSexternal icon.

People with a history of dermal filler use

Infrequently, people who have received dermal fillers might experience swelling at or near the site of filler injection (usually face or lips) following administration of a dose of an mRNA COVID-19 vaccine (no similar occurrences were observed in the Janssen COVID-19 vaccine clinical trials). The swelling appears to be temporary and resolves with medical treatment, including corticosteroid therapy. Any currently FDA-approved or FDA-authorized COVID-19 vaccine can be administered to people who have received injectable dermal fillers who have no contraindications or precautions for vaccination. However, these people should be advised to contact their healthcare professional for evaluation if they experience swelling at or near a dermal filler site following vaccination.

Considerations for use of the Janssen COVID-19 vaccine in certain populations

Thrombosis with thrombocytopenia syndrome

Thrombosis with thrombocytopenia syndrome (TTS) is a rare syndrome that involves acute venous or arterial thrombosis and new onset thrombocytopenia in patients with no recent known exposure to heparin. In the United States, the majority of people with TTS that occurred after Janssen COVID-19 vaccination had clots located in cerebral venous sinuses; clots also occurred in other unusual locations, including in the portal vein and splenic vein, and included a combination of venous and arterial thromboses. FDA updated the Janssen COVID-19 vaccine EUA Fact Sheetexternal icon for Health Care Providers Administering Vaccine (Vaccination Providers) and Fact Sheetexternal icon for Recipients and Caregivers to include information about rare clotting events that might occur after vaccination, primarily among women aged 18–49 years.

Women aged <50 years

The highest rates of TTS per vaccine doses administered were identified in women <50 years of age. Women aged <50 years can receive any currently FDA-approved or FDA-authorized COVID-19 vaccine. However, they should be made aware of the rare risk of TTS after receipt of the Janssen COVID-19 vaccine and the availability of other currently FDA-approved or FDA-authorized COVID-19 vaccines (i.e., mRNA vaccines) for use as a primary series or booster dose. At the time of ACIP’s review, TTS reporting rates to VAERS were 7.0 cases per million Janssen COVID-19 vaccine doses administered to women aged 18−49 years and 0.9 per million to women aged≥50 years.

People with a history of thrombosis or risk factors for thrombosis  

Although the etiology of TTS associated with the Janssen COVID-19 vaccine is unclear, it appears to be similar to another rare immune-mediated syndrome, heparin-induced thrombocytopenia (HIT). For unvaccinated people, until more information becomes available, experts advise that people with a history of an episode of an immune-mediated syndrome characterized by thrombosis and thrombocytopenia, such as HIT, should be offered another currently FDA-approved or FDA-authorized COVID-19 vaccine (i.e., mRNA vaccine) if it has been ≤90 days since their TTS resolved. After 90 days, patients may be vaccinated with any currently FDA-approved or FDA-authorized COVID-19 vaccine.

There are no data on the safety of administering a booster dose of either the Janssen vaccine or an mRNA vaccine to people who had TTS following the first dose. Given the clinical severity of TTS, experts do not recommend administering a second dose of the Janssen vaccine to patients who had TTS after their first dose. These people may receive a dose of an mRNA COVID-19 vaccine as a booster at least 2 months (8 weeks) following their dose of the Janssen vaccine and after their clinical condition has stabilized. Prior to booster vaccination, a conversation between the patient and their clinical team, including hematologists or other specialists, may assist with decisions about using an mRNA COVID-19 vaccine as a booster and the timing of the booster vaccination.

Venous thromboembolism (VTE), defined as deep vein thrombosis, pulmonary embolism, or both, are common. The biologic mechanisms for VTE (as well as arterial thrombi) differ from the underlying immune-mediated mechanism for HIT. Based on current knowledge, experts believe that people with risk factors for VTE (e.g., inherited or acquired thrombophilia including Factor V Leiden; prothrombin gene 20210A mutation; antiphospholipid syndrome; protein C, protein S or antithrombin deficiency), or a prior history of other types of thromboses (including cerebral venous sinus thrombosis [CVST]) not associated with thrombocytopenia are unlikely to be at increased risk for TTS. Likewise, although the risk of thrombosis is increased during pregnancy and the postpartum period, and with certain hormonal contraceptives (e.g., combined oral contraceptives, patch, and ring), experts believe that these factors do not make people more susceptible to TTS after receipt of the Janssen COVID-19 vaccine. People with risk factors for VTE can receive any currently FDA-approved or FDA-authorized vaccine, including the Janssen COVID-19 vaccine.

Use of aspirin or anticoagulants

It is not recommended that people take aspirin or an anticoagulant before vaccination with the Janssen COVID-19 vaccine or any other currently FDA-approved or FDA-authorized COVID-19 vaccine (i.e., mRNA vaccine) unless they take these medications as part of their routine medications.

People with a history of Guillain-Barré syndrome

Reports of adverse events following use of the Janssen COVID-19 Vaccine under EUA suggest an increased risk of GBSexternal icon during the 42 days following vaccination. Investigations to assess whether there is a causal relationship between GBS and Janssen vaccine are ongoing. People with a history of GBS can receive any currently FDA-approved or FDA-authorized COVID-19 vaccine. However, given the possible association between the Janssen COVID-19 vaccine and an increased risk of GBS, a patient with a history of GBS and their clinical team should discuss the availability of mRNA COVID-19 vaccines to offer protection against COVID-19.

There are no data on the safety of administering a booster dose of either Janssen vaccine or an mRNA vaccine to people who had GBS following the first dose of Janssen vaccine. People who had GBS after Janssen vaccine should be made aware of the option to receive an mRNA COVID-19 vaccine booster dose at least 2 months after the Janssen dose. However, Janssen vaccine may still be used as a booster in people with a history of GBS after Janssen vaccine, particularly if the GBS occurrence was outside of the 42 days after vaccination or was assessed as related to a non-vaccine factor. Prior to booster vaccination, a conversation between the patient and their clinical team, including neurologists or other specialists, may assist with decisions about administration of a COVID-19 booster vaccine and timing of the booster vaccination.

Considerations involving pregnancy, lactation, and fertility

COVID-19 vaccination is recommended for all people aged 12 years and older, including people who are pregnant, lactating, trying to get pregnant now, or might become pregnant in the future. Any of the currently FDA-approved or FDA-authorized COVID-19 vaccines can be administered to people in these groups; ACIP and CDC does not state a product preference. This is applicable for a primary series, additional doses, and booster doses. However, all women aged <50 years should be aware of the rare risk of TTS after receipt of the Janssen COVID-19 vaccine and the availability of other currently FDA-approved or FDA-authorized COVID-19 vaccines (i.e., mRNA vaccines for use as a primary series or booster dose) for which this risk has not been seen. See also People with a history of thrombosis or risk factors for thrombosis. There is no evidence that any of the COVID-19 vaccines affect current or future fertility. For purposes of decisions around administering both primary series vaccination and a booster dose, pregnant and recently pregnant people (for at least 42 days following end of pregnancy) should be considered in the same group as people with underlying medical conditions.

Pregnancy

Pregnant and recently pregnant people with COVID-19 are at increased risk for severe illness when compared with non-pregnant people. Severe illness includes illness that requires hospitalization, intensive care unit admission, mechanical ventilation, or extracorporeal membrane oxygenation or illness that results in death, although the absolute risk for these outcomes is low. Additionally, pregnant people with COVID-19 are at increased risk for preterm birth and might be at increased risk for other adverse pregnancy complications and outcomes, such as preeclampsia, coagulopathy, and stillbirth.

A growing body of evidence on the safety and effectiveness of COVID-19 vaccination – in both animal and human studies – indicates that the benefits of vaccination outweigh any known or potential risks of COVID-19 vaccination during pregnancy.

• No safety signals in animal studies: No female reproduction or fetal, embryonal, or postnatal development safety concerns were demonstrated in animals that received Pfizer-BioNTech, Moderna, or Janssen COVID-19 vaccines before or during gestation.
• No adverse outcomes in previous trials of the adenovirus platform that included pregnant people: The adenovirus vector platform used in the Janssen COVID-19 vaccine has been used for other Janssen vaccine development programs in which pregnant people were vaccinated during any trimester, including a large-scale Ebola vaccine trial. No adverse pregnancy-related outcomes—including infant outcomes—were determined to be related to the vaccine in these trials.
• COVID-19 vaccines do not cause infection in the pregnant person or the fetus: The currently FDA-approved or FDA-authorized COVID-19 vaccines (i.e., mRNA vaccines and a non-replicating viral vector vaccine) are not live vaccines and cannot cause infection in either the pregnant person or the fetus.
• Reassuring early safety data on mRNA COVID-19 vaccines during pregnancy: CDC released the first U.S. dataexternal icon on the safety of mRNA COVID-19 vaccines administered during pregnancy. The report analyzed data from three vaccine safety-related databases: VAERSexternal icon, the v-safe active surveillance system, and the v-safe pregnancy registry, which collects additional detailed data on pregnant people and their infants. Early data from these systems did not identify any safety concerns for pregnant people who were vaccinated or their infants. Among pregnant people enrolled in the v-safe pregnancy registry who were vaccinated before 20 weeks’ gestation, miscarriage rates following vaccination were similar to the background incidence of miscarriageexternal icon.
• Early data suggest mRNA COVID-19 vaccines during pregnancy are effective: A studyexternal icon from a large population-based cohort of pregnant people in Israel compared those who received an mRNA COVID-19 vaccination with those who did not and found vaccination was associated with a significantly lower risk of SARS-CoV-2 infection.
• Vaccination of pregnant people generates an immune response: A recent reportexternal icon has shown that mRNA COVID-19 vaccine-induced humoral response was comparable in pregnant women and non-pregnant controls. In the same study, antibodies developed from mRNA COVID-19 vaccination were present in umbilical cord blood, indicating the potential for protection against COVID-19 for neonates and infants.
• Clinical trials to evaluate the safety and efficacy of COVID-19 vaccines in pregnant people are under way: Vaccine manufacturers are also following outcomes in people in the clinical trials who became pregnant.

COVID-19 vaccination is recommended for all people aged 12 years and older, including people who are pregnant. A conversation between the patient and their clinical team may assist with decisions about the use of a COVID-19 vaccine; however, approval by a healthcare professional is not required before vaccination. COVID-19 vaccines and other vaccines may be administered without regard to timing as detailed in Coadministration with other vaccines. If a person becomes pregnant following the first dose of a COVID-19 vaccine that requires two doses (i.e., Pfizer-BioNTech COVID-19 vaccine or Moderna COVID-19 vaccine), the second dose should be administered as indicated for the person to be have maximum protection. Data on uptake of COVID-19 vaccination among pregnant people can be found on CDC’s COVID Data Tracker. Pregnant people are encouraged to enroll in v-safe after COVID-19 vaccination.

Side effects can occur after COVID-19 vaccination in pregnant people, similar to those among non-pregnant people. Acetaminophen can be offered as an option for pregnant people experiencing fever (fever has been associated with adverse pregnancy outcomes) or other post-vaccination symptoms.

Lactation

COVID-19 vaccination is recommended for all people aged 12 years and older, including lactating people. There are limited data on the safety of COVID-19 vaccines in lactating people or the effects of COVID-19 vaccines on the breastfed infant, milk production, and secretion. However, the currently FDA-approved or FDA-authorized COVID-19 vaccines (i.e., mRNA vaccines and a non-replicating viral vector vaccine) cannot cause infection in either the lactating person or the infant. Recent reports have shown that the antibodies developed from mRNA COVID-19 vaccination were present in breastmilk samples. More data are needed to determine if these antibodies convey protection against SARS-CoV-2 infection for neonates and infants.

Fertility

COVID-19 vaccination is recommended for all people aged 12 years and older, including people trying to get pregnant now or who might become pregnant in the future. There is no recommendation for routine pregnancy testing before receipt of a COVID-19 vaccine. Those who are trying to become pregnant do not need to avoid pregnancy after COVID-19 vaccination. There is currently no evidence that any vaccines, including COVID-19 vaccines, cause fertility problems. Many women have become pregnant after receiving COVID-19 vaccine. However, results from ongoing long-term studies are not yet available.

Vaccination of children and adolescents

Adolescents aged 12–17 years are eligible to receive the Pfizer-BioNTech COVID-19 vaccine and may be vaccinated with appropriate consent and assent. Sites administering COVID-19 vaccines should follow current state/jurisdictional policies and practices for other routine immunizations in this age group.

Available safety, immunogenicity, and reactogenicity data are similar to those seen in young adults aged 16-25 years. Syncope (fainting) may occur in association with any injectable vaccines, especially among adolescents. Procedures should be in place to prevent falling injuries and manage syncopal reactions. All people are recommended to be observed for 15 minutes after vaccination (including COVID-19 vaccination); patients should be seated or lying down during the observation period to decrease the risk for injury should they faint. If syncope develops, patients should be observed until symptoms resolve.

Children younger than age 12 years are not eligible to receive the Pfizer-BioNTech COVID-19 vaccine at this time. Children and adolescents younger than age 18 years are not eligible to receive the Moderna or Janssen COVID-19 vaccines at this time.

Patient counseling

The vaccine-specific Fact Sheet for Recipients and Caregiversexternal icon should be provided to all vaccine recipients, parents or guardians, and caregivers (when relevant) before vaccination with any currently FDA-approved or FDA-authorized COVID-19 vaccine.

mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna)

Based on results from manufacturers’ clinical trials, data suggest high vaccine efficacy in preventing symptomatic laboratory-confirmed COVID-19 following receipt of two doses of mRNA COVID-19 vaccine: Pfizer-BioNTech: 91.1% (95% CI: 88.8%, 93.1%) for people aged ≥16 years with approximately 6 months of follow-up and 100% (95% CI: 75.3%, 100%) for adolescents aged 12–15 years with 2 months of follow-up; and Moderna: 94.1% (95% CI: 89.3%, 96.8%) for people aged ≥18 years with 2 months of follow-up. Patients should be counseled on the importance of completing the 2-dose series with the same vaccine product to optimize protection. Data on real-world vaccine effectiveness with the Delta variant (B.1.617.2) as the predominant circulating variant continues to be updated, with early data supporting continued high effectiveness against hospitalization and death and lower effectiveness against confirmed infection and symptomatic disease, compared with the Alpha (B.1.1.7) variant.

Before vaccination, vaccination providers should counsel mRNA COVID-19 vaccine recipients about expected local (e.g., pain, swelling, erythema at the injection site, localized axillary lymphadenopathy⁷ on the same side as the vaccinated arm) and systemic (e.g., fever, fatigue, headache, chills, myalgia, arthralgia) post-vaccination symptoms.

Most systemic post-vaccination symptoms are mild to moderate in severity, occur within the first three days of vaccination resolve within 1–2 days of onset. Overall, symptoms are more frequent and severe following the second dose and among younger people compared with older people (i.e., aged >55 or ≥65 years [for Pfizer-BioNTech or Moderna vaccines, respectively]). People with prior SARS-CoV-2 infection may be more likely to experience symptoms such as fever, chills, and myalgia after the first mRNA COVID-19 vaccine dose. Unless people have a contraindication to vaccination, they should be encouraged to complete the series to optimize protection against COVID-19 even if they experience local or systemic symptoms following the first dose.

Myocarditis and pericarditis

In view of reports of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) after receipt of mRNA COVID-19 vaccines, the fact sheets for the Pfizer-BioNTech COVID-19 vaccineexternal icon and the Moderna COVID-19 vaccineexternal icon include information about myocarditis and pericarditis. For each mRNA vaccine, the Fact Sheet for Recipients and Caregiversexternal icon notes that myocarditis or pericarditis have occurred in some people who have received the vaccine. In most of these people, symptoms began within a few days following receipt of the second dose of the vaccine. The chance of myocarditis or pericarditis occurring after receipt of an mRNA COVID-19 vaccine is very low and can occur in patients with SARS-CoV-2 infection at higher rates than in those who received mRNA vaccines. People should seek medical attention right away if they have any of the following symptoms after receiving the vaccine:

• Chest pain
• Shortness of breath
• Feelings of having a fast-beating, fluttering, or pounding heart

After reviewing benefit-risk assessments for myocarditis and pericarditis after vaccination with mRNA COVID-19 vaccines, ACIP determined that the benefits of using mRNA COVID-19 vaccines clearly outweigh the risks of myocarditis and pericarditis. People receiving mRNA COVID-19 vaccines, especially males aged 12-29 years, should be made aware of both the possibility of myocarditis or pericarditis following receipt of mRNA COVID-19 vaccines and the possibility of myocarditis or pericarditis following SARS-CoV-2 infection, and should be counseled about the need to seek care if symptoms of myocarditis or pericarditis develop after vaccination. Clinicians should consult current clinical guidance for information on the evaluation and management of myocarditis or pericarditis.

Viral vector COVID-19 vaccine (Janssen)

Preliminary data from the manufacturer’s clinical trial suggest an overall efficacy of 66.3% (95% CI: 59.9%, 71.8%) against symptomatic, laboratory-confirmed COVID-19 from ≥14 days after vaccination with the single dose Janssen COVID-19 vaccine in people aged ≥18 years. Vaccine efficacy for the prevention of COVID-19-associated hospitalization was high; vaccine efficacy against hospitalization ≥14 days after vaccination was 93.1% (95% CI: 71.1%, 98.4%). No COVID-19–associated hospitalizations occurred ≥28 days after vaccination in the vaccine group, and 16 occurred in the placebo group (vaccine efficacy = 100%; 95% CI = 74.3%, 100.0%). Vaccine efficacy against all-cause death was 75.0% (95% CI: 33.4%, 90.6%).  Data on real-world vaccine effectiveness with the Delta variant (B.1.617.2) as the predominant variant continue to be updated.

Before vaccination, vaccination providers should counsel Janssen COVID-19 vaccine recipients about expected local (e.g., pain, swelling, erythema at the injection site) and systemic (e.g., fever, fatigue, headache, chills, myalgia, arthralgia) post-vaccination symptoms. Fifty percent of vaccinated people experience at least one local symptom, with pain at the injection site most common, and approximately 55% experience at least one systemic symptom following vaccination. Most systemic post-vaccination symptoms are mild to moderate in severity resolve within 1–2 days post-vaccination. Overall, symptoms were more frequent in people aged 18–59 years compared to people aged ≥60 years.

Thrombosis with thrombocytopenia syndrome

In view of reports of TTS after receipt of the Janssen COVID-19 vaccine, FDA updated the EUAexternal icon fact sheets. The Fact Sheet for Recipients and Caregivers notes that blood clots involving blood vessels in the brain, abdomen, and legs along with low levels of platelets have occurred in some people who received the Janssen COVID-19 vaccine and that these symptoms began approximately 1-2 weeks following vaccination. Most people who developed these blood clots were women aged 18-49 years.⁸ Although the chances of this occurrence are remote, people should seek medical attention right away if they have any of the following symptoms after receiving the Janssen COVID-19 vaccine:

• Shortness of breath
• Chest pain
• Leg swelling
• Persistent abdominal pain
• Severe or persistent headaches or blurred vision
• Easy bruising or tiny blood spots under the skin beyond the site of the injection.

ACIP reviewed a risk-benefit assessment of TTS events after vaccination with the Janssen COVID-19 vaccine. Based on this risk-benefit analysis, ACIP reaffirmed its interim recommendation for the use of the Janssen COVID-19 vaccine in all persons aged ≥18 years, while still acknowledging the increased risk for TTS in women aged <50 years. These women should be made aware of the increased risk for TTS and the availability of other currently FDA-approved or FDA-authorized COVID-19 vaccines (i.e., mRNA vaccines). Clinicians should consult the Health Alert Network (HAN) notification and guidanceexternal icon from the American Society of Hematology for information on the diagnosis and treatment of suspected cases of TTS.

Guillain-Barré Syndrome

Reports of adverse events following use of the Janssen COVID-19 Vaccine under EUA suggest an increased risk of GBSexternal icon during the 42 days following vaccination. The Fact Sheetexternal icon for Recipients and Caregivers includes information about GBS (a neurological disorder in which the body’s immune system damages nerve cells, causing muscle weakness and sometimes paralysis) and notes that in most people symptoms began within 42 days following receipt of Janssen COVID-19 vaccine. Although the chance of GBS occurring is very low, vaccine recipients should seek medical attention right away if they develop any of the following symptoms after receiving Janssen COVID-19 vaccine:

• Weakness or tingling sensations, especially in the legs or arms, that is worsening and spreading to other parts of the body
• Difficulty walking
• Difficulty with facial movements, including speaking, chewing, or swallowing
• Double vision or inability to move eyes
• Difficulty with bladder control or bowel function

ACIP reviewed a benefit-risk assessment of GBSpdf icon events after vaccination with the Janssen COVID-19 vaccine. Based on this benefit-risk analysis, ACIP reaffirmed its interim recommendation for the use of the Janssen COVID-19 vaccine in all persons aged ≥18 years while acknowledging the increased risk for GBS. However, given the possible association between the Janssen COVID-19 vaccine and an increased risk of GBS, a patient with a history of GBS and their clinical team should discuss the availability of mRNA COVID-19 vaccines to offer protection against COVID-19.

Management of post-COVID-19-vaccination symptoms

For all currently FDA-approved or FDA-authorized COVID-19 vaccines, antipyretic or analgesic medications (e.g., acetaminophen, non-steroidal anti-inflammatory drugs) can be taken for the treatment of post-vaccination local or systemic symptoms, if medically appropriate. However, routine prophylactic administration of these medications for the purpose of preventing post-vaccination symptoms is not currently recommended, because information on the impact of such use on COVID-19 vaccine-induced antibody responses is not yet available.

Anaphylactic reactions have been rarely reported following receipt of COVID-19 vaccines. Administration of antihistamines to COVID-19 vaccine recipients before vaccination to prevent allergic reactions is not recommended. Antihistamines do not prevent anaphylaxis, and their use might mask cutaneous symptoms, which could lead to a delay in the diagnosis and management of anaphylaxis. See section on contraindications and precautions to vaccination and interim considerations for anaphylaxis management for more information on management of anaphylaxis.

Infection prevention and control considerations are available for healthcare personnel and long-term care facility residents with systemic signs and symptoms following COVID-19 vaccination.

Contraindications and precautions

Contraindications and precautions to COVID-19 vaccines are described below and summarized in Appendix B. For the purposes of this guidance, an immediate allergic reaction to a vaccine or medication is defined as any hypersensitivity-related signs or symptoms such as urticaria, angioedema, respiratory distress (e.g., wheezing, stridor), or anaphylaxis that occur within four hours following administration.

Healthcare professionals or health departments in the United States can request a consultation from the Clinical Immunization Safety Assessment COVIDvax project about an individual patient residing in the United States for a complex COVID-19 vaccine safety question not readily addressed by CDC guidance.

Contraindications

CDC considers a history of the following to be a contraindication to vaccination with COVID-19 vaccines:

• Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of the COVID-19 vaccine
• Immediate allergic reaction of any severity to a previous dose or known (diagnosed) allergy to a component of the COVID-19 vaccine

See Appendix C for a list of ingredients in COVID-19 vaccines. Polyethylene glycol (PEG) is an ingredient in both mRNA COVID-19 vaccines, and polysorbate 80 is an ingredient in Janssen COVID-19 vaccine. PEG and polysorbate are structurally related, and cross-reactive hypersensitivity between these compounds may occur. People with a contraindication to one of the mRNA COVID-19 vaccines should not receive doses of either of the mRNA vaccines (Pfizer-BioNTech or Moderna). However, people with a contraindication to mRNA COVID-19 vaccines may be able to receive Janssen COVID-19 vaccine, and vice versa, provided certain measures are taken (see “precautions” below). Known polysorbate allergy is no longer a contraindication to mRNA vaccination; however, known polysorbate allergy is a contraindication to Janssen COVID-19 vaccine and thus, a precaution to mRNA COVID-19 vaccination.

Healthcare professionals should attempt to determine whether reactions reported following vaccination are consistent with immediate allergic reactions versus other types of reactions commonly observed following vaccination, such as a vasovagal reaction or post-vaccination side effects (Appendix D). This will help determine which patients have a contraindication to vaccination, including to the second dose of an mRNA COVID-19 vaccine.

Precautions

Most people deemed to have a precaution to a COVID-19 vaccine at the time of their vaccination appointment can and should be administered vaccine. CDC considers a history of an immediate allergic reaction to any vaccine other than COVID-19 vaccine or to any injectable therapy (i.e., intramuscular, intravenous, or subcutaneous vaccines or therapies [excluding subcutaneous immunotherapy for allergies, i.e., “allergy shots”]) as a precaution but not a contraindication to vaccination. People with a history of an immediate allergic reaction to a vaccine or injectable therapy that contains multiple components, one or more of which is a component of a COVID-19 vaccine, have a precaution to vaccination with that COVID-19 vaccine, even if it is unknown which component elicited the allergic reaction.

People with a contraindication to one type of the currently FDA-approved or FDA-authorized COVID-19 vaccines (e.g., mRNA) have a precaution to the other (e.g., Janssen viral vector). However, because of potential cross-reactive hypersensitivity between ingredients in mRNA and Janssen COVID-19 vaccines, consultation with an allergist-immunologist should be considered to help determine if the patient can safely receive vaccination. Healthcare professionals and health departments may also request a consultation from the Clinical Immunization Safety Assessment COVIDvax project. Vaccination of these individuals should only be undertaken in an appropriate setting under the supervision of a healthcare professional experienced in the management of severe allergic reactions.

• People with a contraindication to mRNA COVID-19 vaccines (including due to a known PEG allergy): Consideration may be given to vaccination with Janssen COVID-19 vaccine. People who have received one mRNA COVID-19 vaccine dose but for whom the second dose is contraindicated should wait at least 28 days after the mRNA vaccine dose to receive Janssen COVID-19 vaccine.
• People with a contraindication to Janssen COVID-19 vaccine (including due to a known polysorbate allergy): Consideration may be given to mRNA COVID-19 vaccination. Of note, polysorbate allergy is no longer a contraindication to mRNA COVID-19 vaccination, it is a precaution.

The following considerations can be used to help the vaccination provider conduct a risk assessment for vaccination in individuals with a precaution to vaccination:

• Risk of exposure to SARS-CoV-2 (e.g., because of residence in a congregate setting such as a long-term care settingexternal icon, occupation)
• Risk of severe disease or death due to COVID-19 (e.g., because of age, underlying medical conditions)
• The unknown risk of anaphylaxis (including fatal anaphylaxis) following COVID-19 vaccination in a person with a history of an immediate allergic reaction to other vaccines or injectable therapies
• Ability of the patient to be vaccinated in a setting where appropriate medical care is immediately available for anaphylaxis. Note, for people with a contraindication to one type of COVID-19 vaccines (e.g., mRNA vaccines), vaccination with another type (e.g., Janssen viral vector vaccine) should only be undertaken in an appropriate setting under the supervision of a healthcare professional experienced in the management of severe allergic reactions.

Neither contraindications nor precautions to COVID-19 vaccination

Allergic reactions (including severe allergic reactions) not related to vaccines (COVID-19 or other vaccines) or injectable therapies, such as allergic reactions related to food, pet, venom, or environmental allergies, or allergies to oral medications (including the oral equivalents of injectable medications), are not a contraindication or precaution to COVID-19 vaccination. The vial stoppers of COVID-19 vaccines are not made with natural rubber latex, and there is no contraindication or precaution to vaccination for people with a latex allergy. In addition, because the COVID-19 vaccines do not contain eggs or gelatin, people with allergies to these substances do not have a contraindication or precaution to vaccination.

Delayed-onset local reactions have been reported after mRNA vaccination in some individuals beginning a few days through the second week after the first dose and are sometimes quite large. People with only a delayed-onset local reaction (e.g., erythema, induration, pruritus) around the injection site area after the first vaccine dose do not have a contraindication or precaution to the second dose. These individuals should receive the second dose using the same vaccine product as the first dose at the recommended interval, preferably in the opposite arm.

Observation periods following vaccination

CDC recommends the following observation periods after COVID-19 vaccination:

• 30 minutes:
  • History of an immediate allergic reaction of any severity to other vaccines or injectable therapies
  • People with a contraindication to a different type of COVID-19 vaccine (for example, people with a contraindication to mRNA COVID-19 vaccines who receive Janssen viral vector vaccine should be observed for 30 minutes following Janssen vaccination).
  • History of anaphylaxis due to any cause
• 15 minutes: All other people

Management of anaphylaxis after COVID-19 vaccination

Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of COVID-19 vaccine. Further information on anaphylaxis management can be found in the interim considerations for the management of anaphylaxis following COVID-19 vaccination and laboratory evaluation of people who experience anaphylaxis after vaccination.

Reporting of vaccine adverse events

Adverse events that occur in a recipient following COVID-19 vaccination should be reported to VAERS. Vaccination providers are required by the FDA to report the following that occur after COVID-19 vaccination under BLA or EUA:

• Vaccine administration errors
• Serious adverse events
• Cases of Multisystem Inflammatory Syndrome
• Cases of COVID-19 that result in hospitalization or death

Reporting is encouraged for any other clinically significant adverse event, even if it is uncertain whether the vaccine caused the event. Information on how to submit a report to VAERS is available at https://vaers.hhs.govexternal icon or by calling 1-800-822-7967.

In addition, CDC has developed a new voluntary, smartphone-based tool, v-safe. This tool uses text messaging and web surveys to provide near real-time health check-ins after patients receive COVID-19 vaccination. Reports to v-safe indicating a medically significant health impact, including pregnancy, are followed up by the CDC/v-safe call center to collect additional information to complete a VAERS report, if appropriate.

Laboratory testing

Vaccination and SARS-CoV-2 testing

Antibody testingexternal icon is not currently recommended to assess the need for vaccination in an unvaccinated person or to assess for immunity to SARS-CoV-2 following COVID-19 vaccination. Antibody tests currently authorized under an EUAexternal icon have variable sensitivity, specificity, as well as positive and negative predictive values, and are not authorized for the assessment of immune response in vaccinated people. Furthermore, the serologic correlates of protection have not been established, and antibody testing does not evaluate the cellular immune response, which may also play a role in vaccine-mediated protection.

If antibody testing was performed following vaccination, additional doses of the same or different COVID-19 vaccines are not recommended based on antibody test results at this time. If antibody testing was done after the first dose of an mRNA vaccine, the vaccination series should be completed regardless of the antibody test result.

Interpretation of SARS-CoV-2 test results in vaccinated people

Prior receipt of a COVID-19 vaccine will not affect the results of SARS-CoV-2 viral tests (nucleic acid amplification or antigen tests). To evaluate for evidence of prior infection in vaccinated people (e.g., for public health surveillance or the diagnosis of MIS-C or MIS-A), a test that specifically evaluates IgM/IgG to the nucleocapsid protein should be used.

Use of immune-based tests for tuberculosis infection, such as the tuberculin skin test and interferon-gamma release assay

COVID-19 vaccination should not be delayed because of testing for tuberculosis (TB) infection. Testing for TB infection with one of the immune-based methods, either the tuberculin skin test (TST) or an interferon release assay (IGRA), can be done before, after, or during the same encounter as COVID-19 vaccination.

TSTs and IGRAs were previously recommended to be administered > 4 weeks after completion of COVID-19 vaccination to minimize potential theoretical interference between vaccination and TB testing. This was out of an abundance of caution during a period when these vaccines were new. However, given logistical challenges faced in delaying TB infection testing, the recommendation has been updated so that these tests may now be administered without regard to timing of COVID-19 vaccination.

Footnotes

1. The FDA-approved Pfizer-BioNTech product COMIRNATY and the FDA-authorized Pfizer-BioNTech COVID-19 vaccine have the same formulation and can be used interchangeablyexternal icon. In this document, the terms “Pfizer-BioNTech COVID-19 vaccine” or “Pfizer-BioNTech” refer to both the FDA-approved Pfizer-BioNTech (COMIRNATY) COVID-19 Vaccine and the FDA-authorized Pfizer-BioNTech COVID-19 vaccine.
2. For intervals of 3 months or less, 28 days (4 weeks) is a “month.” For intervals of 4 months or longer, a month is a “calendar month”; e.g., a person who completed the second dose of a 2-dose primary series on April 1, 2021, can receive a booster dose as soon as October 1, 2021.
3. The 4-day grace period should not be used to prospectively schedule or administer a COVID-19 vaccine dose earlier than recommended.
4. WHO has listed the following COVID-19 vaccines for emergency use:
   • Pfizer-BioNTech COVID-19 vaccines (e.g., COMIRNATY, Tozinameran)
   • AstraZeneca-Oxford COVID-19 vaccines (e.g., Covishield, Vaxzevria)
   • Janssen (Johnson & Johnson) COVID-19 vaccine
   • Moderna COVID-19 vaccine
   • Sinopharm BIBP COVID-19 vaccine
   • Sinovac-CoronaVac COVID-19 vaccine

   This list will be updated as additional COVID-19 vaccines receive an emergency use listing from WHOexternal icon.

5. See National Institute of Health (NIH) COVID-19 Treatment Guidelinesexternal icon; Infectious Disease Society of America (IDSA) Guidelines on the Treatment and Management of Patients with COVID-19external icon. 
6. In a post-marketing observational study of people vaccinated with Shingrix (a vaccine for prevention of herpes zoster [shingles]), ~3-6 excess GBS cases per 1 million doses administered to persons ≥65 years in the 6 weeks after vaccination were observed. Although a causal relationship has not been established, FDA added a new warning about GBS in the Prescribing Informationexternal iconexternal icon for Shingrix.
7. The Society of Breast Imaging has developed “Recommendations for the Management of Axillary Adenopathy in Patients with Recent COVID-19 Vaccination”pdf iconexternal iconpdf iconexternal icon which includes considerations for patients and healthcare professionals in scheduling screening exams in relation to the administration of a COVID-19 vaccine.
8. At the time of publication of ACIP’s updated recommendations, all cases of TTS after FDA-authorization of the Janssen COVID-19 vaccine occurred in females. One case of CVST with thrombocytopenia occurred in a male, aged 18–49 years, during the Janssen COVID-19 vaccine Phase III clinical trial.

Appendix A. Vaccine administration errors and deviations

A vaccine administration error is any preventable event that may cause or lead to inappropriate use of vaccine or patient harm. This appendix provides resources for preventing and reporting COVID-19 vaccine administration errors, as well as actions to take after an error has occurred. For completeness, this includes additional scenarios that deviate from CDC recommendations for vaccine intervals but are not considered administration errors. This document is intended to assist vaccination providers with handling exceptional situations in which a vaccination error or deviation has already occurred and may be updated when additional information becomes available.

The recommendations in the table below apply to all FDA-approved or FDA-authorized COVID-19 vaccines and all doses (i.e., primary series, additional dose, booster dose), unless otherwise stated.

Currently, no more than 3 COVID-19 vaccine doses are recommended to be administered (see exceptions for certain moderately and severely immunocompromised people and recipients of hematopoietic cell transplant and CAR-T cell therapy.  For a dose that is repeated due to an administration error (using the guidance in the table below), the dose given in error does not count toward the maximum number of doses. The repeated dose does count toward the 3-dose maximum.

For all vaccine administration errors:

• Inform the recipient of the vaccine administration error.
• Consult with the state immunization program and/or immunization information system (IIS) to determine how the dose should be entered into the IIS, both as an administered dose and to account for inventory.
• Report the error to the Vaccine Adverse Event Reporting System (VAERS), unless otherwise indicated in the table. Providers are required to report all COVID-19 vaccine administration errors—even those not associated with an adverse event—to VAERS. To file an electronic report, please see the VAERS websiteexternal icon.
• Determine how the error occurred and implement strategies to prevent it from happening again. A discussion on strategies to prevent errors can be found in the “Vaccine Administration” chapter of Epidemiology and Prevention of Vaccine-Preventable Diseases (Pink Book). Additional resources can be found on CDC’s vaccine administration web page, including a job aid for preventing errors.

Table. Interim recommendations for COVID-19 vaccine administration errors and deviations

Table. Interim recommendations for mRNA COVID-19 vaccine administration errors and deviations

Type	Administration error/deviation	Interim recommendation
Site/route	Incorrect site (i.e., site other than the deltoid muscle [preferred site] or anterolateral thigh [alternate site])	Do not repeat dose.*
	Incorrect route (e.g., subcutaneous)	Do not repeat dose.* Inform the recipient of the potential for local and systemic adverse events.
Age	Unauthorized age group	If received dose at age less than 12 years, do not give any additional dose at this time.∞ If age 12 to 17 years and a vaccine other than Pfizer-BioNTech was inadvertently administered: If Moderna vaccine administered as the first dose, it is suggested to give Pfizer-BioNTech vaccine as the second dose (at least 28 days after the Moderna vaccine dose) because Pfizer-BioNTech is authorized in this age group. If Janssen vaccine administered, do not repeat dose with Pfizer-BioNTech vaccine.
Dosage	Higher-than-authorized dose volume administered	Do not repeat dose.*†
	Lower-than-authorized dose volume administered (e.g., leaked out, equipment failure, recipient pulled away)	Repeat dose immediately (no minimum interval).* However, if a half-volume formulation of vaccine is administered on the same clinic day to a patient recommended for the full volume formulation, another half-volume dose can be administered, and the two doses can count as one full dose.
Storage and handling	Dose administered after improper storage and handling (e.g., temperature excursion, more than allowed time after first vial puncture)	Contact the manufacturer for information on the stability of the vaccine. If the manufacturer does not have data to support the stability of the vaccine, repeat the dose immediately (no minimum interval).
	Dose administered past the expiration/beyond-use date	Contact the manufacturer for information on the stability of the vaccine. If the manufacturer does not have data to support the stability of the vaccine, repeat the dose immediately (no minimum interval).
Administration	Dose administered within 90 days of monoclonal antibodies or convalescent plasma for COVID-19 treatment	Do not repeat COVID-19 vaccine dose. If person has already received one mRNA COVID-19 vaccine dose, defer administration of second dose for 90 days following receipt of antibody therapy. This deviation from CDC guidance does not require VAERS reporting.
Intervals	Second mRNA dose administered fewer than 17 days (Pfizer-BioNTech) or fewer than 24 days (Moderna) after the first mRNA dose (i.e., administered earlier than the 4-day grace period)	Repeat dose. The repeat dose should be spaced after the improperly spaced dose by the minimum interval (i.e., 21 days after the improperly spaced dose for Pfizer-BioNTech and 28 days after the improperly spaced dose for Moderna).
	The interval between the incorrect administration of an initial single dose of an mRNA COVID-19 vaccine and Janssen COVID-19 vaccine is fewer than 24 days from the mRNA dose.	Do not administer a second primary dose of the mRNA vaccine.§ Person is considered fully vaccinated against COVID-19 ≥2 weeks after receipt of the single dose of Janssen vaccine
	Second dose of an mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) administered at any interval after the recommended interval	Do not repeat dose. There is no maximum interval.  This deviation from CDC guidance does not require VAERS reporting.
	For people with moderate to severe immune compromise, the additional dose (i.e., third dose) of an mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) is administered fewer than 24 days after the second dose (i.e., administered earlier than the 4-day grace period)	Repeat dose. The repeat dose should be spaced after the improperly spaced dose by the minimum interval (i.e., 28 days after the improperly spaced dose).
	Any product is administered as a booster dose fewer than 6 months after a 2-dose primary mRNA series in a person who is not moderately and severely immunocompromised.	Do not repeat dose.
	Any product is administered as a booster dose fewer than 2 months after 1 dose of Janssen COVID-19 primary vaccine	Do not repeat dose.
Mixed series	Incorrect mRNA COVID-19 vaccine product inadvertently administered for second dose in 2-dose primary series	Do not repeat dose.§
Diluent (Pfizer-BioNTech only)	ONLY diluent administered (i.e., sterile 0.9% sodium chloride)	Administer the authorized dose immediately (no minimum interval).#
	No diluent, resulting in higher than authorized dose (i.e., 0.3 ml of undiluted vaccine administered)	Do not repeat dose*† Inform the recipient of the potential for local and systemic adverse events.
	Incorrect diluent type (e.g., sterile water, bacteriostatic 0.9% NS)	Contact the manufacturer for information on the stability of the vaccine. If the manufacturer does not have information to support the stability of the vaccine, repeat the dose immediately (no minimum interval).
	Incorrect diluent volume (i.e., the vial contents were diluted with a diluent volume other than 1.8 ml, but a 0.3 ml dose was still administered)	If dilution results in a higher-than-authorized dose, do not repeat dose and inform the recipient of the potential for local and systemic adverse events.*† If dilution results in a lower-than-authorized dose, repeat dose immediately (no minimum interval).*

Pfizer-BioNTech and Moderna vaccines only:

^*If dose given in error is:

• The first dose, then a second dose should be administered at the recommended interval (21 days [Pfizer-BioNTech] or 28 days [Moderna]).
• The second dose, then the primary series is complete. If an additional dose is indicated in an immunocompromised person, administer it 28 days after the second dose. If a booster dose is indicated in eligible people, administer it 6 months after the second dose.

^∞Do not administer the second dose until the person becomes eligible to receive vaccination (either by reaching the authorized age or if the authorization is extended to include additional age groups), even if this results in the second dose being administered after the recommended interval between doses.

^#If the dose given in error is the first dose, the second dose should be administered at the recommended interval (21 days [Pfizer-BioNTech] or 28 days [Moderna]) from the date of receipt of the valid dose (not the date of receipt of the erroneous dose).

^†If the administration error resulted in a higher-than-authorized vaccine dose, in general the second dose may still be administered at the recommended interval. However, if local or systemic side effects following vaccination are clinically concerning (outside of the expected side effect profile), lead to serious adverse reactions, or are ongoing at the time of the second dose, the decision to administer the second dose may be assessed on a case-by-case basis.

^§CDC provides considerations for a mixed primary series in exceptional circumstances, although a mixed primary series is not authorized under the vaccine Emergency Use Authorizationsexternal icon. If a mixed primary series is given intentionally (e.g., due to exceptional circumstances), VAERS reporting is NOT required.

^‡The additional mRNA COVID-19 vaccine dose should be the same vaccine product as the initial 2-dose series. However, if a different product is given intentionally (i.e., the vaccine product administered for the first 2 doses is not available), VAERS reporting is NOT required.

Appendix B: Triage of people with a history of allergies or allergic reactions

Appendix: Triage of persons presenting for Pfizer-BioNTech COVID-19 vaccination

CONTRAINDICATION TO COVID-19 VACCINATION	PRECAUTION TO COVID-19 VACCINATION	MAY PROCEED WITH COVID-19 VACCINATION
History of the following: Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of a COVID-19 vaccine† Immediate allergic reaction* of any severity after a previous dose or known (diagnosed) allergy to a component of a COVID-19 vaccine†	Among people without a contraindication, a history of: Any immediate allergic reaction* to other vaccines or injectable therapies‡ Note: people with a contraindication to mRNA COVID-19 vaccines have a precaution to Janssen COVID-19 vaccine, and vice versa. See footnote for additional information on additional measures to take in these people.#	Among people without a contraindication or precaution, a history of: Allergy to oral medications (including the oral equivalent of an injectable medication) History of food, pet, insect, venom, environmental, latex, etc., allergies Family history of allergies
Actions: Do not vaccinate. Consider referral to allergist-immunologist. Consider other vaccine alternative.†#	Actions: Risk assessment Consider referral to allergist-immunologist 30-minute observation period if vaccinated	Actions: 30-minute observation period: people with history of anaphylaxis (due to any cause) 15-minute observation period: all other people

† See Appendix C for a list of ingredients. People with a contraindication to one of the mRNA COVID-19 vaccines should not receive doses of either of the mRNA vaccines (Pfizer-BioNTech or Moderna).
* Immediate allergic reaction to a vaccine or medication is defined as any hypersensitivity-related signs or symptoms consistent with urticaria, angioedema, respiratory distress (e.g., wheezing, stridor), or anaphylaxis that occur within four hours following administration.
‡People with a history of an immediate allergic reaction to a vaccine or injectable therapy that contains multiple components, one or more of which is a component of a COVID-19 vaccine, have a precaution to vaccination with that COVID-19 vaccine, even if it is unknown which component elicited the allergic reaction.
#Polyethylene glycol (PEG) is an ingredient in both mRNA COVID-19 vaccines, and polysorbate 80 is an ingredient in Janssen COVID-19 vaccine. PEG and polysorbate are structurally related, and cross-reactive hypersensitivity between these compounds may occur. People with a contraindication to mRNA COVID-19 vaccines (including due to a known allergy to PEG) have a precaution to Janssen COVID-19 vaccine. Among people who received one mRNA COVID-19 dose but for whom the second dose is contraindicated, consideration may be given to vaccination with Janssen COVID-19 vaccine (administered at least 28 days after the mRNA COVID-19 dose). People with a contraindication to Janssen COVID-19 vaccine (including due to a known allergy to polysorbate) have a precaution to mRNA COVID-19 vaccines. For people with these precautions, referral to an allergist-immunologist should be considered. Healthcare professionals and health departments may also request a consultation from the Clinical Immunization Safety Assessment COVIDvax project. In patients with these precautions, vaccination should only be undertaken in an appropriate setting under the supervision of a healthcare professional experienced in the management of severe allergic reactions.

Appendix C: Ingredients included in COVID-19 vaccines

The following is a list of ingredients for the Pfizer-BioNTechexternal icon, Modernaexternal icon, and Janssenexternal icon COVID-19 vaccines reported in the prescribing information for each vaccine.*

 

Ingredients included in Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines

Description	Pfizer-BioNTech (mRNA)	Moderna (mRNA)	Janssen (viral vector)
Active ingredient	Nucleoside-modified mRNA encoding the viral spike (S) glycoprotein of SARS-CoV-2	Nucleoside-modified mRNA encoding the viral spike (S) glycoprotein of SARS-CoV-2	Recombinant, replication-incompetent Ad26 vector, encoding a stabilized variant of the SARS-CoV-2 Spike (S) protein
Inactive ingredients	2[(polyethylene glycol (PEG))-2000]-N,N-ditetradecylacetamide	PEG2000-DMG: 1,2-dimyristoyl-rac-glycerol, methoxypolyethylene glycol	Polysorbate-80
	1,2-distearoyl-sn-glycero-3-phosphocholine	1,2-distearoyl-sn-glycero-3-phosphocholine	2-hydroxypropyl-β-cyclodextrin
	Cholesterol	Cholesterol	Citric acid monohydrate
	(4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)	SM-102: heptadecan-9-yl 8-((2-hydroxyethyl) (6-oxo-6-(undecyloxy) hexyl) amino) octanoate	Trisodium citrate dihydrate
	Sodium chloride	Tromethamine	Sodium chloride
	Monobasic potassium phosphate	Tromethamine hydrochloride	Ethanol
	Potassium chloride	Acetic acid
	Dibasic sodium phosphate dihydrate	Sodium acetate
	Sucrose	Sucrose

* None of the vaccines contain eggs, gelatin, latex, or preservatives. All COVID-19 vaccines are free from metals such as iron, nickel, cobalt, lithium, rare earth alloys or any manufactured products such as microelectronics, electrodes, carbon nanotubes, or nanowire semiconductors.
Note: Both the Pfizer-BioNTech and Moderna COVID-19 vaccines contain polyethylene glycol (PEG). PEG is a primary ingredient in osmotic laxatives and oral bowel preparations for colonoscopy procedures, an inactive ingredient or excipient in many medications, and is used in a process called “pegylation” to improve the therapeutic activity of some medications (including certain chemotherapeutics). Additionally, cross-reactive hypersensitivity between PEG and polysorbates (included as an excipient in some vaccines and other therapeutic agents) can occur. Information on active or inactive ingredients for vaccines and medications can be found in the package insert. CDC’s vaccine excipient summarypdf icon and the National Institutes of Health DailyMed databaseexternal icon can also be used as a resource.

Appendix D: Potential characteristics of allergic reactions, vasovagal reactions, and vaccine side effects following COVID-19 vaccination

In patients who experience post-vaccination symptoms, determining the etiology (including allergic reaction, vasovagal reaction, or vaccine side effects) is important to determine whether a person can receive additional doses of the vaccine (including the second dose of an mRNA COVID-19 vaccine). The following table of signs and symptoms is meant to serve as a resource but might not be exhaustive, and patients might not have all signs or symptoms. Vaccination providers should use their clinical judgement when assessing patients to determine the diagnosis and management.

Appendix D: Potential characteristics of allergic reactions, vasovagal reactions, and vaccine side effects following COVID-19 vaccination

Characteristic	Allergic reactions (including anaphylaxis)	Vasovagal reaction	Vaccine side effects (local and systemic)
Timing after vaccination	Most occur within 15-30 minutes of vaccination	Most occur within 15 minutes	Median of 1 to 3 days after vaccination (with most occurring the day after vaccination)
Signs and symptoms
Constitutional	Feeling of impending doom	Feeling warm or cold	Fever, chills, fatigue
Cutaneous	Skin symptoms present in ~90% of people with anaphylaxis, including pruritus, urticaria, flushing, angioedema	Pallor, diaphoresis, clammy skin, sensation of facial warmth	Pain, erythema, or swelling at injection site; lymphadenopathy in same arm as vaccination
Neurologic	Confusion, disorientation, dizziness, lightheadedness, weakness, loss of consciousness	Dizziness, lightheadedness, syncope (often after prodromal symptoms for a few seconds or minutes), weakness, changes in vision (such as spots of flickering lights, tunnel vision), changes in hearing	Headache
Respiratory	Shortness of breath, wheezing, bronchospasm, stridor, hypoxia	Variable; if accompanied by anxiety, might have an elevated respiratory rate	N/A
Cardiovascular	Hypotension, tachycardia	Variable; might have hypotension or bradycardia during syncopal event	N/A
Gastrointestinal	Nausea, vomiting, abdominal cramps, diarrhea	Nausea, vomiting	Vomiting or diarrhea might occur
Musculoskeletal	N/A	N/A	Myalgia, arthralgia
Vaccine and clinical management recommendations
If vaccinated with mRNA COVID-19 vaccine as first dose, recommended to receive second mRNA vaccine dose?	No; see Appendix B	Yes	Yes

References

• The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine — United States, December 2020
• The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Moderna COVID-19 Vaccine — United States, December 2020
• The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Janssen COVID-19 Vaccine — United States, February 2021
• Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients—United States, April 2021
• The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine in Adolescents Aged 12–15 years — United States, May 2021
• Use of mRNA COVID-19 Vaccine After Reports of Myocarditis Among Vaccine Recipients: Update from the Advisory Committee on Immunization Practices — United States, June 2021
• Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices — United States, July 2021pdf icon
• Use of Pfizer-BioNTech COVID-19 Vaccine in Persons Aged ≥16 Years: Recommendations of the Advisory Committee on Immunization Practices — United States, September 2021
• Pfizer-BioNTech COVID-19 Vaccine Fact Sheet for Healthcare Providers (fda.gov)external icon
• Moderna COVID-19 Vaccine EUA Fact Sheet for Healthcare Providers (fda.gov)external icon
• Janssen COVID-19 Vaccine EUA Fact Sheet for Healthcare Providers (fda.gov)external icon
• ACIP General Best Practice Guidelines for Immunization
• Interim considerations: preparing for the potential management of anaphylaxis after COVID-19 vaccination