Interim Clinical Considerations for Use of COVID-19 Vaccines

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, Emergency Use Instructions (EUI) for FDA-approved 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 consulted when using the Pfizer-BioNTechexternal icon, Modernaexternal icon, and Janssenexternal icon COVID-19 vaccines. Additional vaccine product-specific information is also available.

COVID-19 vaccines

Three COVID-19 vaccinespdf icon are currently approved under a BLA or authorized under an EUA by FDA (BOX 1):

Pfizer-BioNTech COVID-19 Vaccine/COMIRNATY (hereafter referred to as Pfizer-BioNTech in this document) 1

Moderna COVID-19 Vaccine

Janssen (Johnson & Johnson) COVID-19 Vaccine

The Pfizer-BioNTech and Moderna vaccines are lipid nanoparticle-formulated, nucleoside-modified mRNA vaccines encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. The Janssen COVID-19 Vaccine is a recombinant, replication-incompetent adenovirus type 26 (Ad26) vector encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2. None of the currently FDA-approved or FDA-authorized COVID-19 vaccines are live-virus vaccines.

Box 1. Regulatory terminology for COVID-19 vaccinesexternal icon Emergency Use Authorizationexternal icon (EUA): Mechanism to facilitate the availability and use of medical products, including vaccines, during public health emergencies, such as the current COVID-19 pandemic. Under an EUA, the U.S. Food and Drug Administration (FDA) can make a product available to the public based on the best available evidence, without waiting for all the evidence that would be needed for FDA approval. FDA Approvedexternal icon: FDA-approved vaccines have undergone the agency’s standard process for reviewing the quality, safety and effectiveness of medical products included in a manufacturer’s submission of a Biologics License Applicationexternal icon (BLA)—a comprehensive document that addresses specific requirements. Emergency Use Instructionsexternal icon (EUI): Provision of the 2013 Pandemic and All-Hazards Preparedness Reauthorization Act which gives CDC legal authority to create and issue EUI to permit emergency use of FDA-approved medical products. The EUI consist of Fact Sheets to inform healthcare providers and recipients about such products’ approved, licensed, or cleared conditions of use, and may provide information about emergency use of FDA-approved medical products that is not be included in or differs in some way from the information provided in the FDA-approved labeling (package insert).

Groups recommended for vaccination

COVID-19 vaccination is recommended for everyone ages 5 years and older in the United States for the prevention of SARS-CoV-2 infection. However, the age groups approved under BLA or authorized under EUA to receive vaccination vary by vaccine product. ACIP and CDC have issued recommendations for COVID-19 vaccine use including primary series vaccination, an additional primary dose, and a booster dose, as defined below (BOX 2).

There is currently no FDA-approved or FDA-authorized COVID-19 vaccine for children ages 4 years and younger. Ongoing clinical trials of COVID-19 vaccine in these children are examining a range of vaccine doses that are lower than the doses authorized for people ages 5 years and older. Data from these trials will be used to determine the optimal dose to protect children ages 4 years and younger while minimizing potential adverse events. These children should not receive any COVID-19 vaccine doses (including partial doses of vaccine formulations approved or authorized for people ages 5 years and older) at this time unless part of a clinical trial.

Box 2. Terminology for COVID-19 vaccine dosingexternal icon Primary series: 2-dose series of an mRNA COVID-19 vaccine (Pfizer-BioNTech and Moderna) or a single dose of Janssen vaccine Additional primary dose: A subsequent dose of vaccine administered to people who likely did not mount a protective immune response after initial vaccination. An additional primary mRNA COVID-19 vaccine dose is recommended for moderately or severely immunocompromised people who received a 2-dose mRNA vaccine primary series. Booster dose: A subsequent dose of vaccine administered to enhance or restore protection by the primary vaccination which might have waned over time. Homologous booster dose: The same vaccine product used for the booster dose as was administered for the primary series Heterologous booster dose (mix-and-match booster): The vaccine product used for the booster dose differs from the product administered for the primary series

Interim clinical considerations regarding the use of specific vaccines, dosage and administration, specific populations and situations, and contraindications and precautions are summarized in the sections that follow. 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.

Primary series

COVID-19 vaccines are administered intramuscularly. An mRNA COVID-19 vaccine series is preferred over Janssen COVID-19 Vaccine for primary vaccination. Vaccine providers should start the two-dose mRNA COVID-19 vaccine series even if there is uncertainty about whether or when the patient will receive their recommended second dose. Two-dose mRNA COVID-19 vaccines are feasible for use in most vaccine-eligible populations or settings. However, offering the Janssen COVID-19 Vaccine is preferable to not providing any COVID-19 vaccine. Completion of more than one COVID-19 primary series is not recommended, except in people who were vaccinated before or during treatment with a hematopoietic cell transplant (HCT) or chimeric antigen receptor (CAR)-T-cell therapy.

A person is considered fully vaccinated with vaccines against SARS-CoV-2 infection ≥2 weeks after receipt of the second dose in a 2-dose series (Pfizer-BioNTech and Moderna) or ≥2 weeks after receipt of a single dose of the Janssen COVID-19 Vaccine. CDC recommends that people remain up to date with their vaccines, which includes additional doses for individuals who are immunocompromised or booster doses at regular time points. Individuals who are moderately or severely immunocompromised should get an additional primary shot and a booster shot.

People who have a contraindication to vaccination or who otherwise do not complete a primary vaccination series are not considered fully vaccinated.

TABLE 1. COVID-19 vaccines: primary series and additional primary dose

TABLE 1. COVID-19 vaccines: primary series doses and additional primary doses Vaccine manufacturer Age indication Vial cap color denoting formulation Dose Injection volume Number of doses in primary series (interval between doses) Additional primary dose in immunocompromised people (interval since second dose) Pfizer-BioNTech 5–11 years Orange 10 µg 0.2 mL 2 (21 days) 1 (≥28 days) Pfizer-BioNTech ≥12 years Purple or gray 30 µg 0.3 mL 2 (21 days) 1 (≥28 days) Moderna ≥18 years Not applicable 100 µg 0.5 mL 2 (28 days) 1 (≥28 days) Janssen ≥18 years Not applicable 5×1010 viral particles 0.5 mL 1 (Not applicable) Not applicable

mRNA COVID-19 vaccines

Pfizer-BioNTech COVID-19 Vaccine is administered as a primary series of 2 doses 21 days apart. Prior to administration, vaccination providers should ensure the correct age-appropriate formulation is administered (Table 1). Pfizer-BioNTech COVID-19 Vaccine is supplied as three different formulationspdf icon distinguished by different colored vial caps.

There are two formulations of Pfizer-BioNTech that are FDA-approved for use in people age 16 years and older and FDA-authorized for use in people age 12-15 years:

A formulation supplied in a multiple dose vial with a purple cap (some vials also have a label with a purple border), and which must be diluted prior to use. It uses phosphate buffered saline (PBS). Each diluted 0.3 mL dose contains 30 µg of modified mRNA.

(some vials also have a label with a purple border), and which prior to use. It uses phosphate buffered saline (PBS). Each diluted 0.3 mL dose contains 30 µg of modified mRNA. A formulation supplied in a multiple dose vial with a gray cap and label with a gray border, and which that does not require dilution prior to use. It uses tromethamine (Tris) buffer. Each 0.3 mL dose contains 30 µg of modified mRNA.

For children age 5-11 years, the Pfizer-BioNTech 10 µg formulation is FDA-authorized for primary vaccination. It is supplied in a with an orange cap and label with an orange border and must be diluted before use. It uses a Tris buffer. Each diluted 0.2 mL dose contains 10 µg of modified mRNA.

Moderna COVID-19 Vaccine is FDA-authorized for use in people ages 18 years and older. It is administered as a primary series of 2 doses 28 days apart. Each 0.5 mL primary series dose contains 100 µg of modified mRNA. The FDA-authorized booster dose is 0.25mL and contains 50 µg of modified mRNA.

Interval between mRNA COVID-19 primary vaccine doses2

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. The 4-day grace period should not be used to prospectively schedule or administer a COVID-19 vaccine dose earlier than recommended.3 If the second dose of an mRNA 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] after the first dose), the second dose should be repeated. The repeat dose should be spaced based on the date of the dose given in error by the recommended minimum interval (see Appendix A for more details).

Janssen COVID-19 Vaccine is FDA-authorized for use in people ages 18 years and older. It is administered as a single dose (0.5 mL) for primary vaccination. Although mRNA vaccines are preferentially recommended in most situations over the Janssen COVID-19 Vaccine, the Janssen COVID-19 Vaccine may be considered in some situations. See Considerations for Janssen COVID-19 Vaccine and Contraindications and precautions.

Additional primary dose

Antibody response after vaccines, including COVID-19 vaccines, may be suboptimal in people with altered immunocompetence at the time of vaccination. Moderately or severely immunocompromised people who received an initial mRNA COVID-19 vaccine primary series should receive an additional primary dose of the same mRNA COVID-19 vaccine as was administered for the primary series. An additional dose should be administered as follows:

Pfizer-BioNTech: 30 µg in a volume of 0.3 mL (purple or gray cap formulation) for people ages 12 years and older 10 µg in a volume of 0.2 mL (orange cap formulation) for people ages 5–11 years

Moderna: 100 µg in a volume of 0.5 mL for people ages 18 years and older

The additional primary 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 series (see Considerations for COVID-19 vaccination in moderately or severely immunocompromised people).2,3 The 4-day grace period should not be used to prospectively schedule or administer a COVID-19 vaccine dose earlier than recommended. If the additional primary 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 primary dose should be repeated. The repeat dose should be spaced from the date of the dose given in error by the recommended minimum interval (see Appendix A for more details).

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

Janssen COVID-19 Vaccine is not authorized for use as an additional primary dose and people who received a single-dose Janssen primary vaccine should not receive an additional primary dose. They should receive a booster dose.

The sections on People who received COVID-19 vaccine outside the United States and People who received COVID-19 vaccine as part of a clinical trial should be consulted for additional primary dose recommendations in these groups.

Booster dose

All people ages 12 years and older should receive a booster dose of COVID-19 vaccine (Table 2), even if they were age 11 years or younger at the time of the primary series. Among people ages 18 years and older, use of an mRNA COVID-19 vaccine for a booster dose is preferred (Moderna or Pfizer-BioNTech) even for those who received Janssen COVID-19 Vaccine for their single dose primary series. However, if an mRNA vaccine cannot be given, offering the Janssen COVID-19 Vaccine as a booster is preferable to not providing any COVID-19 vaccine booster. In people ages 12–17 years, only Pfizer-BioNTech COVID-19 vaccine can be used for the booster dose.

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

Currently, CDC does not recommend a booster dose in children ages 5–11 years, regardless of other characteristics or medical conditions. As more data from studies on long-term protection become available, these recommendations may be updated. Please consult sections on People who received COVID-19 vaccine outside of the United States and People who received COVID-19 vaccine as part of a clinical trial for booster dose recommendations for these groups.

Interval between primary series and booster doses2

The interval for booster vaccination should follow the interval recommended for the primary series (Table 2). People ages 18 years and older who received Janssen primary vaccination should preferably receive an mRNA vaccine booster dose at least 2 months (8 weeks) later. See Considerations for Janssen COVID-19 Vaccine. If the booster dose is given earlier than the 4-day grace period3, it does not need to be repeated.

mRNA COVID-19 vaccine primary series recipients: Recipients of an mRNA COVID-19 vaccine primary series (including those who received two doses of different mRNA vaccine products) should receive a single booster dose at least 5 months after the last dose administered.

For people ages 18 years and older, an mRNA COVID-19 vaccine is preferred over the Janssen COVID-19 Vaccine for booster vaccination. However, recipients of an mRNA vaccine primary series who are ages 18 years and older and who are unable to receive an mRNA booster dose can be offered a Janssen vaccine booster dose after discussion of the benefits and risks (See Considerations for Janssen COVID-19 Vaccine ) . The recommended interval for the booster dose is based on primary series (i.e., 5 months after mRNA primary vaccination or 2 months after Janssen primary vaccination). For people ages 12–17 years, only Pfizer-BioNTech COVID-19 Vaccine can be used for booster vaccination at this time.

Janssen COVID-19 Vaccine primary series (single dose) recipients: Recipients of the single dose Janssen COVID-19 Vaccine for primary vaccination should receive a single COVID-19 vaccine booster dose at least 2 months (8 weeks) after the primary dose. An mRNA COVID-19 vaccine is preferred over the Janssen COVID-19 Vaccine for booster vaccination.

Dosing

The following vaccine-specific booster dose and volume should be administered regardless of whether the vaccine is homologous (same dose as primary series) or heterologous (different than primary series).

Pfizer-BioNTech (purple cap or gray cap): 30 µg in a volume of 0.3 mL (same dose as the primary series dose and additional primary dose).

Moderna: 50 µg in a volume of 0.25 mL. This is a different dose than what is used for the primary series dose and the additional primary dose.

Janssen: 5×1010 viral particles in a volume of 0.5 mL (same dose as the primary series dose)

TABLE 2. COVID-19 vaccines: booster dose by primary series

TABLE 2. COVID-19 vaccines: booster dose by primary series Vaccine completed for primary series Authorized age for vaccine booster Interval between last primary dose (including additional dose, when applicable) and booster dose Number of doses Injection volume and product that may be given as booster dose*† Pfizer-BioNTech ≥12 years ≥5 months 1 0.3 mL Pfizer-BioNTech*, or 0.25 mL Moderna, or 0.5 mL Janssen† Moderna ≥18 years ≥5 months 1 0.25 mL Moderna, or 0.3 mL Pfizer-BioNTech, or 0.5 mL Janssen† Janssen ≥18 years ≥2 months 1 0.5 mL Janssen†, or 0.3 mL Pfizer-BioNTech, or 0.25 mL Moderna

*Only Pfizer BioNTech can be used as a booster dose in those ages 12–17 years.

†Use of an mRNA vaccine for a booster dose is preferred over Janssen vaccine.

Interchangeability of COVID-19 vaccine products

In general, the same mRNA vaccine product (i.e., the same manufacturer) should be used for all doses in the primary series, including an additional primary dose.

However, use of heterologous booster doses (mix and match) is authorized for those 18 years and older. One studypdf icon showed that a booster dose using any of the three FDA-approved or FDA-authorized COVID-19 vaccines led to a strong serologic response, regardless of which of the three vaccines was used for primary vaccination. For a given COVID-19 primary vaccine series, heterologous boosters elicited similar or higher antibody responses as compared to their respective homologous booster responses.

In addition, for some people who received certain non-FDA-approved or -authorized vaccines outside of the United States or as part of a clinical trial, an additional heterologous primary dose and heterologous booster dose using Pfizer-BioNTech are allowed under EUI.

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

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

For people ages 18 years and older, 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 product may be administered at a minimum interval of 28 days between doses to complete the mRNA COVID-19 vaccination series. 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 people are considered fully vaccinated with COVID-19 vaccines ≥2 weeks after receipt of the second dose of an mRNA vaccine and should be offered an additional primary dose or booster dose, if indicated.

The FDA-approved COMIRNATY and the two EUA authorized formulations of Pfizer-BioNTech COVID-19 Vaccine for people ages 12 years and older (purple cap and gray cap), when prepared according to their respective instructions for use, can be used interchangeablyexternal icon and should only be used for people ages 12 years and older. The Pfizer-BioNTech COVID-19 Vaccine formulation (10 µg in 0.2 mL) with an orange cap vial should only be used for children ages 5–11 years. See additional information on vaccine administration errors and deviations in Appendix A.

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 if the person is age 18 years or older. As part of a pre-vaccination discussion with a vaccination provider, all people who elect to receive a Janssen COVID-19 Vaccine booster should be informed about the risk and symptoms of thrombosis with thrombocytopenia syndrome (TTS), and the need to seek immediate medical care should TTS symptoms develop. 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 with COVID-19 vaccines ≥2 weeks after receipt of the single dose of the Janssen COVID-19 Vaccine.

Coadministration of COVID-19 vaccines with other vaccines

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. If multiple vaccines are administered at a single visit, administer each injection in a different injection site. For people ages 11 years and older, the deltoid muscle can be used for more than one intramuscular injection administered at different sites in the muscle. For children ages 5–10 years, if more than two vaccines are injected in a single limb, the vastus lateralis muscle of the anterolateral thigh is the preferred site because of greater muscle mass.

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 vaccine and vaccines that may be more likely to cause a local reaction in different limbs, if possible.

See general best practices and Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book) for further information.

People who received COVID-19 vaccine outside the United States

There are four scenarios outlined below.

People who received COVID-19 vaccine as part of a clinical trial

Participants in clinical trials within or outside the United States who received all of the recommended primary series doses of a WHO-EUL COVID-19 vaccine4 (i.e., not placebo) that is not FDA-approved or FDA-authorized or a vaccine that is not listed for emergency use by WHO4 but for which a U.S. data and safety monitoring board or equivalent has independently confirmed efficacy are considered fully vaccinated. At this time, only the Moderna COVID-19 Vaccine in children ages 6–17 and the Medicago COVID-19 Vaccine in people ages 18 years and older meet these criteria.

Moderately or severely immunocompromised clinical trial participants ages 12 years and older should receive an additional primary dose of Pfizer-BioNTech COVID-19 Vaccine at least 28 days after receiving the second vaccine dose of their primary series as detailed in the Considerations for COVID-19 vaccination in moderately or severely immunocompromised people , unless they have received or plan to receive an additional or booster dose through a clinical trial.

unless they have received or plan to receive an additional or booster dose through a clinical trial. Clinical trial participants ages 12 years and older (including moderately or severely immunocompromised people who received an additional primary dose) should receive a single booster dose of Pfizer-BioNTech COVID-19 Vaccine, unless they have received or plan to receive a booster dose through a clinical trial.

receive a single booster dose of Pfizer-BioNTech COVID-19 Vaccine, unless they have received or plan to receive a booster dose through a clinical trial. If clinical trial participants have questions about whether they should receive an additional and/or booster dose outside of the clinical trial, they should consult with their healthcare provider. Clinical trial participants who did not receive all the recommended doses, or who received other vaccines not listed above, should consult with their healthcare provider to determine if they should receive an FDA-approved or FDA-authorized COVID-19 vaccine series.

COVID-19 vaccination and SARS-CoV-2 infection

People with prior or current SARS-CoV-2 infection

COVID-19 vaccination is recommended for everyone ages 5 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 primary 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. Present data are insufficient to determine an antibody titer threshold that indicates when an individual is protected from SARS-CoV-2 infection. There is neither any FDA-authorized or FDA-approved test nor any other scientifically validated strategy that providers or the public can use to reliably determine whether a person is protected from infection.

Data from multiple studies 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. Current evidence suggests that the risk of SARS-CoV-2 reinfection is low after a previous infection but may increase with time due to waning immunity. Among individuals infected with SARS-CoV-2, substantial heterogeneity exists in their immune response. Conversely, the immune response following COVID-19 vaccination is more 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 recovery from the acute illness (if symptoms were present) has been achieved and criteria to discontinue isolation have been met. 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 people with a history of MIS-C or MIS-A may be at risk for an MIS-like illness following vaccination with COVID-19 vaccine.

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 (e.g., specialist in infectious diseases, rheumatology, or cardiology) 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 risk of myocarditis following COVID-19 vaccination for people who meet all of the following criteria:

Clinical recovery has been achieved, including return to normal cardiac function; It has been ≥90 days since their diagnosis of MIS-C; 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 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:

An increased personal risk of severe COVID-19 (e.g., age, underlying conditions) 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 people who received any COVID-19 vaccine should be reported to VAERSexternal icon .

People who received passive antibody products

Currently, there are limited data available on the safety and effectiveness of COVID-19 vaccines in people who received passive antibody products (anti-SARS-CoV-2 monoclonal antibodies or convalescent plasma) as part of COVID-19 treatment or post-exposure prophylaxis. Based on the estimated half-life of such products and the anticipated period of protection against infection (when receiving anti-SARS-CoV-2 monoclonal antibodies for post-exposure prophylaxis) or reinfection (when receiving passive antibody therapy for treatment), COVID-19 vaccination should be temporarily deferred as a precautionary measure during the time period specified below after receiving passive antibody products to avoid potential interference of the product with vaccine-induced immune responses:

Passive antibody product used for post-exposure prophylaxis: Defer COVID-19 vaccination for 30 days

Passive antibody product used for COVID-19 treatment: Defer COVID-19 vaccination for 90 days

However, if passive antibody products and a COVID-19 vaccine dose are administered within these recommended deferral periods (30 or 90 days), the vaccine dose does not need to be repeated.

For people receiving antibody products 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.

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. Vaccines for diseases other than COVID-19 can be administered without regard to timing following receipt of convalescent plasma except for measles- or varicella-containing vaccines, which should be administered at least 7 months after receipt of convalescent plasma.

Vaccinated people who subsequently develop COVID-19

COVID-19 treatment-specific clinical guidelines (such as those published by the National Institutes of Healthexternal icon and the Infectious Diseases Society of Americaexternal icon) 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.

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

COVID-19 vaccines are not recommended for post-exposure prophylaxis to prevent SARS-CoV-2 infection. Unvaccinated people who were close contacts of a person with SARS-CoV-2 infection should typically not seek vaccination until quarantine has ended; this is to reduce the risk of transmission to others (e.g., healthcare personnel, other clinic patients), because vaccination is not expected to prevent SARS-CoV-2 infection that could occur after the exposure for which the person is in quarantine, and to avoid confusion between vaccination side effects and symptoms of COVID-19.

However, to avoid missed opportunities for vaccination, vaccination during quarantine could be considered during outreach and contact tracing activities or at the time of post-exposure SARS-CoV-2 testing in certain circumstances. Examples might include when people 1) are likely to have repeated SARS-CoV-2 exposures because they are unable to effectively quarantine (e.g., residing in a congregate or crowded setting or during outbreaks in their community), or, 2) will have limited access to vaccination after their quarantine period has ended, or, 3) are unlikely to otherwise seek vaccination after their quarantine period has ended. In such situations, the person recommended for quarantine can receive vaccination as long as 1) they do not have symptoms consistent with COVID-19, and, 2) appropriate infection prevention and control procedures are employed during vaccination. Furthermore, unvaccinated people who are being tested for SARS-CoV-2 may be candidates for same-day vaccination if they do not have symptoms consistent with COVID-19.

People should be counseled that COVID-19 vaccines are effective, especially at preventing serious COVID-19 illnesses. However, they should also be informed that vaccination may not prevent SARS-CoV-2 infection until 2 weeks after the primary series is completed, i.e., will not prevent them from getting COVID-19 from the current exposure but should help protect them from infection after future exposures. In addition, SARS-CoV-2 viral testing may be necessary to differentiate between common post-vaccination symptoms and symptoms of SARS-CoV-2 infection:

People who develop signs and symptoms not associated with the COVID-19 vaccination (e.g., cough, shortness of breath, runny nose, sore throat, loss of taste or smell) should isolate and be evaluated for SARS-CoV-2 infection as soon as possible.

People who develop signs and symptoms that could be from either COVID-19 vaccination or SARS-CoV-2 infection (e.g., fever, fatigue, headache, myalgia) without typical COVID-19 symptoms described above, and are clinically stable, should isolate and, if symptoms do not improve by two days post-vaccination, be evaluated for SARS-CoV-2 infection.

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

Immunocompromised people ages 5 years and older should receive a primary COVID-19 vaccine series as soon as possible; for those 18 years and older, mRNA COVID-19 vaccines are preferred over the Janssen COVID-19 Vaccine. 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.

Moderately or severely immunocompromised people may not mount a protective immune response after initial vaccination and, furthermore, their protection by primary vaccination may wane over time making them susceptible to severe SARS-CoV-2 infection. ACIP and CDC have made age-specific recommendations for an additional primary dose and a booster dose for this population.

Description of moderate and severe immunocompromising conditions and treatment

Moderate and severe immunocompromising 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 hematopoietic cell transplant (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/mm 3 , history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV)

, 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 primary dose for people who are not moderately or severely immunocompromised is currently unknown.

ACIP’s 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, can be consulted for additional information about the degree of immune suppression associated with different medical conditions and treatments. CDC’s Interim Clinical Considerations, however, should be used to guide timing for COVID-19 vaccination (primary series, additional primary dose, and booster dose) in people with moderate or severe immunocompromise.

Recommendations for an additional primary dose of an mRNA COVID-19 vaccine in moderately or severely immunocompromised people after an initial 2-dose mRNA COVID-19 vaccine series

Moderately or severely immunocompromised people ages 5 years and older (Pfizer-BioNTech vaccine recipients) or ages 18 years and older (Moderna recipients) should receive an additional primary dose of the same mRNA COVID-19 vaccine administered for the primary series ≥28 days after completion of the initial 2-dose series.3 The additional primary mRNA COVID-19 dose should be the same vaccine product as the initial 2-dose mRNA COVID-19 primary series (Pfizer-BioNTech or Moderna).

Janssen COVID-19 Vaccine is not authorized for use as an additional primary dose, and people who received a single-dose Janssen COVID-19 primary vaccine should not receive an additional primary dose. However, they should receive a booster dose.

Recommendations for a COVID-19 booster dose in people ages 12 years and older who are moderately or severely immunocompromised

Moderately or severely immunocompromised people ages 12 years and older who received an mRNA COVID-19 vaccine primary series and an additional primary mRNA vaccine dose should receive a single COVID-19 booster dose (preferably with an mRNA COVID-19 vaccine) at least 5 months after completing their additional primary dose.

If a moderately or severely immunocompromised person age 12 years or older has received two primary mRNA vaccine doses but has not yet received an additional mRNA primary dose, they should first receive the additional age-appropriate primary dose (at least 28 days after the second dose), followed by a single age-appropriate COVID-19 vaccine booster dose (at least 5 months after the additional primary dose). For people ages 12–17 years, the age appropriate COVID-19 primary series and booster dose can only be with the Pfizer BioNTech COVID-19 Vaccine.

Moderately or severely immunocompromised people ages 18 years and older who received a single dose Janssen COVID-19 Vaccine primary series should receive a single COVID-19 vaccine booster dose two or more months after the first dose, preferably with an mRNA vaccine instead of the Janssen vaccine.

The sections on People who received COVID-19 vaccine outside the United States and People who received COVID-19 vaccine as part of a clinical trial should be consulted for booster dose recommendations in these groups.

Considerations for COVID-19 revaccination

HCT and CAR-T-cell recipients who received doses of COVID-19 vaccine prior to or during treatment with an HCT or CAR-T-cell therapy should be revaccinated with a primary vaccine series, preferably with an mRNA vaccine regardless of vaccine issued for initial primary vaccination, at least 3 months (12 weeks) after transplant or CAR-T-cell therapy.

An additional primary 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 people who continue to have moderate or severe immune compromise. The additional primary dose of an mRNA COVID-19 vaccine should be administered at least 28 days after the second dose. A patient’s clinical team is best positioned to determine the degree of immune compromise and appropriate timing of vaccination.

Considerations for timing of COVID-19 vaccination in relation to immunosuppressive therapies

Whenever possible, COVID-19 vaccines should be administered 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 for administration of the primary series, additional primary dose, booster dose, and COVID-19 revaccination (HCT and CAR-T-cell recipients).

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 primary dose) has not been established. Serologic testing or cellular immune testing outside of the context of research studies is not recommended at this time.

Reinforcement of the need for prevention measures among immunocompromised people

Vaccinated people who are immunocompromised (including people who receive an additional primary dose or a booster dose) 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 involving pregnancy, lactation, and fertility

COVID-19 vaccination is recommended for people who are pregnant, lactating, trying to get pregnant now, or who might become pregnant in the near future. mRNA vaccines are recommended for all vaccine-eligible populations, including for people who are pregnant or lactating. Those who are considering receipt of the Janssen COVID-19 Vaccine should be counseled about the rare risk of TTS which can occur (typically within 2 weeks) after receipt of the Janssen COVID-19 Vaccine, and need for a booster dose 2 months or more after the initial dose. 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.

Pregnancy

Although the overall risks are low, pregnant and recently pregnant people (for at least 42 days following the end of pregnancy) 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 stillbirth and might be at increased risk for other pregnancy complications.

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.

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.

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. data external icon on the safety of mRNA COVID-19 vaccines administered during pregnancy. The report analyzed data from three vaccine safety-related databases: VAERS external 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 late in their pregnancy or their infants. Additional studies examined data from people who received an mRNA vaccine before 20 weeks’ gestation and found no increased risk for miscarriage external icon .

on the safety of mRNA COVID-19 vaccines administered during pregnancy. The report analyzed data from three vaccine safety-related databases: VAERS , 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 late in their pregnancy or their infants. Additional studies examined data from people who received an mRNA vaccine before 20 weeks’ gestation and found no increased risk for miscarriage . Early data suggest mRNA COVID-19 vaccines during pregnancy are effective: A study external icon from a large population-based cohort of pregnant people in Israel compared those who received mRNA COVID-19 vaccination with those who did not and found vaccination was associated with a significantly lower risk of SARS-CoV-2 infection.

from a large population-based cohort of pregnant people in Israel compared those who received 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 report external 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.

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.

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 vector 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 vaccination is recommended for all 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 for the primary series (i.e., Pfizer-BioNTech or Moderna), the second dose should be administered as indicated for the person to 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 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 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 fertility studies are not yet available.

Vaccination of children and adolescents

The COVID-19 pandemic has had significant impacts on the health and well-being of children. While children and adolescents are less likely to develop severe COVID-19 compared to older adults, severe illness (i.e., hospitalization, intensive care unit admission, death), and complications of SARS-CoV-2 infection (e.g., MIS-C, post-COVID conditions) do occur in this population. Among children and adolescents with severe COVID-19, no identifiable risk factor, such as an underlying medical condition, has been reported for approximately one third of cases. In addition, SARS-CoV-2 infection or exposure results in other negative impacts, such as school absences and social isolation.

COVID-19 vaccine recommendations for children and adolescents

Children and adolescents ages 5–17 years are recommended to receive the age-appropriate formulation of a COVID-19 primary vaccine series. At this time, the 2-dose Pfizer-BioNTech primary series is the only FDA-approved or FDA-authorized vaccine for children and adolescents ages 5–17 years. Although many children and adolescents may have experienced prior SARS-CoV-2 infectionpdf icon, COVID-19 primary vaccination is recommended for everyone ages 5 years and older, regardless of a history of underlying medical conditions, symptomatic or asymptomatic SARS-CoV-2 infection, or seropositivity.

Datapdf icon from clinical trials in children indicate that Pfizer-BioNTech vaccines can be given safely to children with evidence of a prior SARS-CoV-2 infection. Data, predominately from adults, suggests that protection from SARS-CoV-2 reinfection is high after initial infection but decreases with time due to waning immunity. Growing epidemiologic evidence from adults and adolescents indicates that vaccination following infection further increases protection from subsequent infection, including in the setting of increased circulation of more infectious variants. Serologic testingexternal icon to assess for prior infection is not recommended for the purpose of vaccine decision-making. More information on vaccination after SARS-CoV-2 infection can be found here.

Moderately or severely immunocompromised people ages 5 years and older (Pfizer-BioNTech recipients) or ages 18 years and older (Moderna recipients) should receive an additional primary dose of the mRNA COVID-19 vaccine administered for the primary series.

Adolescents ages 12–17 years should receive a single booster dose of Pfizer-BioNTech COVID-19 Vaccine at least 5 months after completion of the primary series. Booster doses are not recommended for people ages 11 years and younger at this time.

Children and adolescents may be vaccinated with appropriate consent and assent. Sites administering COVID-19 vaccines should follow current state/jurisdictional policies and practices for other routine vaccinations in this age group.

Dosing and formulation

Children should receive the age-appropriate vaccine formulation regardless of their size or weight. Children ages 5–11 years should receive the 10 µg Pfizer-BioNTech COVID-19 Vaccine (orange cap) formulation and adolescents ages 12 years and older should receive the 30 µg Pfizer-BioNTech COVID-19 Vaccine (purple or gray cap) formulation. In contrast to many medications, vaccine dosages (for COVID-19 vaccines and for other routinely recommended vaccines) are based on age and not size or weight. Different dosages are evaluated during vaccine development to determine the lowest effective dose for the target age group. Clinical trials evaluate various dosing regimens to determine the best dosage and schedule that produces an adequate immune response which is both safe and effective.

Children should receive the vaccine dosage and formulation based on their age on the day of vaccination with each dose. If a child turns 12 years old between their first and second dose, they should receive the age-appropriate 30 µg Pfizer-BioNTech COVID-19 Vaccine (purple or gray cap) formulation for their second dose to complete their series. However, the FDA authorizationexternal icon allows children who will turn from age 11 years to 12 years between their first and second dose in the primary regimen to receive, for either dose, either: (1) the Pfizer-BioNTech COVID-19 Vaccine formulation for children ages 5–11 years (each 0.2 mL dose containing 10 µg in an orange cap vial); or (2) the Pfizer-BioNTech COVID-19 Vaccine formulation authorized for use in individuals ages 12 years and older (each 0.3 mL dose containing 30 µg in a purple cap or gray cap vial). If such dosing occurred, the child is considered fully vaccinated. This is not considered an error and VAERS reporting is not indicated.

Reactogenicity and adverse events

Available safety and immunogenicity data for Pfizer-BioNTech COVID-19 vaccines in children and adolescents are similar to those seen in young adults. Local and systemic reactions following vaccination are less frequentpdf icon in children ages 5–11 years compared with young adults ages 16–25 years.

Syncope (fainting) may occur in association with any injectable vaccine, especially in adolescents. Procedures should be in place to prevent falling injuries and manage syncopal reactions. People should be seated or lying down during vaccination. Vaccine providers, particularly when vaccinating adolescents, should consider observing vaccine recipients for 15 minutes after vaccination to decrease the risk for injury should they faint. If syncope develops, patients should be observed until symptoms resolve.

Myocarditis is a rare, serious adverse event that has been reported primarily after receipt of the second dose of mRNA COVID-19 vaccines, with the highest risk currently observed in males ages 12–29 years. FDA has authorized and ACIP and CDC have recommended Pfizer-BioNTech vaccines in children ages and adolescents ages 12–17 years based on the determination that the benefits of COVID-19 vaccination outweigh risks in these populations. More information on myocarditis and COVID-19 vaccination can be found here.

Administration errors

If a child age 5–11 years inadvertently receives a 30 µg dose of Pfizer-BioNTech COVID-19 Vaccine for their first dose, a single, age-appropriate dose should be administered as a second dose 21 days later. If a child age 5–11 years inadvertently receives a 30 µg dose for their second dose, the primary series is considered complete, and no subsequent doses are recommended. If a person age 12–17 years inadvertently receives a 10 µg dose of Pfizer-BioNTech COVID-19 Vaccine (ages 5–11 years formulation), the dose does not need to be repeated. However, based on clinical judgement (e.g., the adolescent received two doses of the incorrect formulation), a repeat dose of Pfizer-BioNTech COVID-19 Vaccine (ages 12 years and older formulation [30 µg]) may be administered at an interval of 21 days after the dose given in error. If the dose given in error is the first dose, administer the second Pfizer-BioNTech COVID-19 Vaccine (ages 12 years and older formulation [30 µg]) 21 days later to complete the primary series. See above section on “Dosing and formulation” for further information on children who will turn from age 11 years to 12 years between their first and second dose.

Information on preventing, reporting, and managing COVID-19 vaccine administration errors is found in Appendix A. Administration errors should be reported to VAERSexternal icon.

Children younger than age 5 years are not eligible to receive the Pfizer-BioNTech COVID-19 Vaccine at this time unless part of a clinical trial. Children and adolescents younger than age 18 years are not eligible to receive the Moderna or Janssen COVID-19 vaccines at this time unless part of a clinical trial.

Patient counseling

Pre-vaccination counseling

The vaccine-specific Fact Sheet for Recipients and Caregivers (Pfizer-BioNTech,external icon Modernaexternal icon, Janssenexternal 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. They should be informed that mRNA vaccines are preferred over the Janssen COVID-19 Vaccine and that there is a risk of TTS following receipt of this vaccine. Those who elect to receive a Janssen COVID-19 Vaccine should be informed about the risk and symptoms of TTS that can occur, (typically in the 2 weeks after vaccination) as well as the need to seek immediate medical care should symptoms develop.

Potential for local and systemic reactions

Before vaccination, providers should counsel COVID-19 vaccine recipients, parents, or guardians about expected local (e.g., pain, swelling, erythema at the injection site) and systemic (e.g., fever, fatigue, headache, chills, myalgia, arthralgia) post-vaccination reactions. Localized axillary lymphadenopathy5 on the same side as the vaccinated arm has been observed following vaccination with mRNA COVID-19 vaccines. Routine prophylactic administration of antipyretic or analgesic medications (e.g., acetaminophen, non-steroidal anti-inflammatory drugs) for the purpose of preventing post-vaccination symptoms is not recommended.

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 generally recommended. However, while antihistamines will not prevent anaphylaxis, some experts advise antihistamine use as a means of preventing milder allergic reactions in patients who might be at higher risk for allergic reactions.

Use of aspirin or anticoagulants

It is not recommended that people take aspirin or an anticoagulant before vaccination with any currently FDA-approved or FDA-authorized COVID-19 vaccine, including Janssen COVID-19 Vaccine, unless they take these medications as part of their routine medications.

Management of post-COVID-19-vaccination symptoms

For all currently FDA-approved or FDA-authorized COVID-19 vaccines, antipyretic or analgesic medications can be taken for the treatment of post-vaccination local or systemic symptoms, if medically appropriate. However, in general, aspirin is not recommended for use in children and adolescents ages 17 years and younger as an antipyretic or analgesic due to the risk of Reye’s syndrome.

Additional guidance is available for assessing and responding to post-vaccination signs and symptoms in workplaces, including healthcare settings, and among long-term care facility residents.

Special populations

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 but, as with the general population, mRNA vaccines are preferred over the Janssen COVID-19 Vaccine. If people with these conditions are immunocompromised because