Healthcare Professionals: COVID-19 Vaccination Information Update March 2022

COVID-19 vaccines were approved more rapidly than other vaccines. How can you reassure patients about this expedited approval process?

COVID vaccines were developed at a rapid pace. This does NOT mean safety steps were skipped.³⁴ The process was expedited because of the pandemic.³⁴

COVID-19 vaccines are going through the same RIGOROUS approval process as other approved vaccines. Data are reviewed/analyzed by independent experts (i.e., not scientists employed by the manufacturer). The independent reviewer recommendations are then presented to the approving agency (e.g., FDA, Health Canada).⁵⁰

Reassure patients that COVID-19 vaccine safety is a top priority.^27,31 Monitoring is ongoing (e.g., V-SAFE^a)^.

• Explain that in addition to standard monitoring (e.g., vaccine adverse event reporting system [VAERS]) additional monitoring is being done.

Some of the COVID vaccines use new technology. How can you reassure patients these newer vaccines are safe?

Available COVID-19 vaccines are new types of vaccines.^22,35 Explain how they work:^22,35

• mRNA vaccines give our cells a blueprint for how to make a piece of a SARS-CoV-2 “spike” protein (note this piece of the SARS-Co-V-2 “spike protein” is harmless to the vaccine recipient). This triggers an immune response. Once the blueprint is delivered, the messenger (mRNA) is broken down.
• Viral vector vaccines use a weakened version (e.g., non-replicating, modified) of a different live virus with a viral vector (genetically inserted material from COVID-19). The virus used poses no threat of causing illness in humans because of the modification or because the type of virus cannot cause disease in humans. The viral vector teaches the vaccinated person’s body to build cells to fight COVID-19.
• Plant-based vaccines use plants to produce protein-like virus particles (VLPs).  The body mounts an immune response to the VLPs.  If infected with the virus in the future, the body will recognize and fight the virus.¹⁰⁸
• Protein subunit vaccines use the COVID-19 “spike” protein to tell the immune system to make T-lymphocytes and antibodies. If infected in the future, memory cells will recognize and fight the virus.¹⁰⁴

Explain that available COVID-19 vaccines do NOT contain the SARS-CoV-2 virus.^6,17,22,35

Reassure patients that available COVID-19 vaccines do NOT affect a person’s genetic material (DNA).^22,35

What are some talking points to use with patients who may be hesitant to get vaccinated for COVID-19?

Remind patients about the benefits of COVID-19 vaccination. Vaccination may:¹⁶

• reduce illness severity if you become infected with COVID-19.
• protect friends, family, co-workers, and close contacts from getting COVID-19.
• allow people to start doing more (e.g., eating at restaurants, gathering with vaccinated people without masks).

Explain that the COVID-19 vaccine is one important tool in the toolbox to end the pandemic.^16,93

• Social distancing and masks reduce the chance of exposure to the coronavirus that causes COVID-19.⁹³
• Vaccination gets your immune system ready to fight COVID-19 infection if exposed.¹⁶
• Vaccination is also an important step in the development of herd immunity.²¹
  • Herd immunity is when it is unlikely that a bacteria or virus can spread and cause disease because a large enough proportion of people are protected or considered immune.²¹ More data are needed to know how many people need to be protected to achieve herd immunity against COVID-19.²¹ Some predict that at least 70% of the worldwide population would need to be vaccinated to achieve herd immunity, but the threshold may be higher with variants.³²

Encourage vaccination as the safer path toward immunity.

• There is no way to predict COVID-19 infection severity for anyone, and infections can be fatal.^4,16
• COVID-19 infection has been associated with long-term consequences, even in healthy adults and children (e.g., lung, heart, and memory problems; mood changes; kidney damage).^4,5
• Tell patients that we don’t know how long infection-induced immunity (antibodies from an infection) or vaccine-induced immunity (antibodies from vaccination) lasts.^11,31 Immunity varies in duration.
• Explain that in adults, data suggest vaccine-induced immunity protects against reinfection five times better than a previous COVID-19 infection.⁹⁰

What do we know about safety and efficacy of COVID-19 vaccine in children?

At the time of publication, there are no COVID-19 vaccines authorized for children younger than 5 years old. See our chart, COVID-19 Vaccines, for which vaccines and doses are approved or authorized for specific age groups.

Early data suggest the Pfizer-BioNTech vaccine 10 mcg per dose, two-dose series (separated by 21 days) is safe (similar side effects as older patients) and effective in children five to 11 years old (~90% effective at preventing symptomatic COVID-19 compared to placebo).^42,80

• Data are being collected for use in younger children, as young as six months old.⁷¹

Encourage vaccination in eligible children and adolescents.

• Children and teens can get COVID-19, including severe cases and complications (e.g., “long-haul” COVID, Multisystem Inflammatory Syndrome in Children [MIS-C]).^42,49,89
  • About one-third of hospitalized children with COVID-19 require care in the intensive care unit (ICU).⁷²
  • More than half of children who had COVID-19, still have at least one symptom lasting ≥120 days.⁸⁹
• Vaccinating children may reduce transmission to relatives or immunocompromised friends or family.

Follow laws and regulations regarding parental consent for childhood vaccination. In the U.S. state-specific minor consent laws can be found at https://www.vaxteen.org/consent-laws-by-state.

What dose should a child receive if they turn 12 years old in between the first and second COVID-19 vaccine dose?

COVID-19 vaccine doses are based on the child’s age on the date of vaccination.⁴⁹

• Children 5 to 11 years old should receive a 10 mcg dose of the Pfizer-BioNTech COVID-19 vaccine.^42,49
• Children ≥12 years old should receive a 30 mcg dose of the Pfizer-BioNTech COVID-19 vaccine.^42,49

If a child who turns 12 years old after the first vaccine dose happens to receive a 10 mcg dose of the Pfizer-BioNTech COVID-19 vaccine as their second dose, the child is still considered fully vaccinated two weeks after the second dose.⁴⁹

What do we know about the efficacy of COVID-19 vaccines against COVID-19 variants?

Currently available COVID-19 vaccines are highly effective at preventing severe disease, hospitalization, and death from SARS-CoV-2, including the Delta and Omicron variants, especially after receiving a COVID-19 booster dose.^20,65

Fully vaccinated people can experience breakthrough infections and then spread the virus to others, though it appears that vaccinated people spread the SARS-CoV-2 virus for a shorter time compared to unvaccinated people.⁶⁵

Variants of the SARS-CoV-2 virus are expected to continue to emerge.⁶⁵ Studies are ongoing to assess the ability of vaccines to continue to provide protection.⁶⁴

What are common expected short-term adverse effects with COVID-19 vaccination?

Be transparent that patients may experience short-term adverse effects after vaccination (i.e., don’t downplay these). This has been helpful to ensure patients return for their second dose of other vaccines (e.g., Shingrix).

• Younger adults may be more likely than older patients to experience side effects.⁴¹ Children may experience fewer side effects than adolescents and young adults.⁹¹
• Most patients can expect mild to moderate injection-site pain/soreness (redness/swelling are less likely).^15,18,33,41
• Many patients experience systemic reactions (more likely with the second dose), within ~2 days of vaccination. These usually go away within a day or two.³³ This is a normal response to a vaccine and means the body is building antibodies to prevent infection.^7,41
• Example systemic reactions from COVID-19 vaccines include:^{1,41,79,81,82}
  • fatigue/malaise/headache
  • fever/chills
  • myalgia/arthralgia
• Early data suggest that reactions with booster doses or additional doses are similar to reactions from the initial series and most symptoms seem mild to moderate.^3,12,52
• Syncope or fainting has been reported after nearly all vaccines (not just COVID-19 vaccines).

What can patients do to minimize expected vaccine adverse effects?

Help patients reduce and prepare for adverse effects. For example:

• CDC and Health Canada support use of antipyretic or analgesic meds (e.g., acetaminophen, ibuprofen) AFTER VACCINATION TO TREAT SYMPTOMS from a COVID-19 vaccine. However, routine use of prophylactic acetaminophen before or after vaccination with a COVID-19 vaccine is not recommended.^49,69
• Suggest that patients get vaccinated when they will have a few days to rest and recover (i.e., on a Friday if they don’t work weekends).

What rare or serious side effects are associated with BOTH types of COVID-19 vaccines?

Serious adverse effects from COVID-19 vaccination seem extremely rare.⁴ If a safety issue is identified, it will be evaluated to see if it is related to the vaccine.⁴

There have been reports of severe allergic reactions, including possible anaphylaxis, after receiving mRNA or viral vector COVID-19 vaccines.^{45,47,58,76,82} Anaphylaxis is a known, but rare side effect with any vaccine.^45,58,76

What rare or serious side effects are associated with mRNA COVID-19 vaccines?

Rare/serious side effects noted with mRNA COVID-19 vaccines include:

• The rate of Bell’s palsy seen after COVID-19 vaccination was NOT more than is expected in the general population. Patients who have previously had Bell’s palsy may receive a COVID-19 vaccine.^1,8,49
• Myocarditis and pericarditis have been reported almost exclusively after an mRNA vaccine.^57,61 In the U.S. these cases have typically occurred after the second dose, been mild, resolved with medications, and are most often (there have been some cases in females) seen in adolescent and young adult males (e.g., ≥16 years old).⁶¹ Cases in Canada were more evenly distributed after first or second doses.⁵⁷ Reports will continue to be investigated.^57,61
  • Educate patients that the risk of myocarditis associated with COVID-19 infection is much higher (~150 cases per 100,000 patients) than the risk associated with vaccination.^28,29 In the U.S., expected maximum number of myocarditis cases per million second doses of an mRNA COVID-19 vaccine per age group:²⁸
    • 12 to 17 years old: ~70
    • 18 to 24 years old: ~56
    • 25 to 29 years old: ~20
    • 30 years and older: ~4
  • No cases of myocarditis were reported in a study in over 3,000 patients between the ages of 5 to 11 years old within seven days of the second dose of the Pfizer-BioNTech COVID-19 vaccine. Note the baseline risk for myocarditis is lower for this age group than for adolescents.⁹¹
  • In Canada, the Pfizer-BioNTech (Comirnaty) vaccine is preferred over Moderna (SpikeVax) for patients:⁴²
    • between 12 to 29 years old to start or complete an mRNA COVID-19 vaccine series. Note: it is preferred to give second doses eight weeks after the first dose as a longer interval between doses may lower the risk of myocarditis/pericarditis.
    • between 18 to 29 years old receiving a booster shot.

What rare or serious side effects are associated with viral vector COVID-19 vaccines?

Rare/serious side effects noted with viral vector COVID-19 vaccines include:

• Transverse myelitis has been noted. Monitoring for events will continue.⁴⁴
• Guillain-Barre syndrome (GBS):^49,82 History of GBS is NOT a COVID-19 vaccination contraindication.^49,69
• There are reports of rare blood clots occurring along with a low platelet count (e.g., cerebral venous sinus thrombosis [CVST]) after receiving a dose of the AstraZeneca/Vaxzevria (authorized in Canada; seen in males and females, and more commonly after the first dose) and Janssen/J&J (seen more commonly in females between 30 and 49 years old) vaccines.^49,57,69 Limited data suggest clot risk is NOT higher with booster doses.¹⁹ It’s being referred to as thrombosis with thrombocytopenia syndrome (TTS).⁴⁹ However, the risk of clotting is much higher with SARS-CoV-2 infection.⁸⁸
  • Encourage patients who notice symptoms suggestive of blood clots or low platelets, especially ≤3 weeks from vaccination with a viral vector vaccine, to seek medical care right away. Symptoms can include:⁴⁹
    • symptoms of a blood clot (e.g., shortness of breath, abdominal or leg pain, redness, warmth, swelling)
    • neurologic symptoms (e.g., severe headache, blurred vision)
    • new or easy bruising
    • petechiae (tiny red spots on the skin)

What are contraindications to receiving a COVID-19 vaccine?

Contraindications to a COVID-19 vaccine includes:^{38,49,58,69,79,101}

• history of a severe allergic reaction (e.g., anaphylaxis) after a dose of the same type of COVID-19 vaccine (e.g., mRNA, viral vector).
  • Patients who experience anaphylaxis after an mRNA COVID-19 vaccine should NOT receive any other mRNA COVID-19 vaccine.
  • Patients who experience anaphylaxis after a viral vector COVID-19 vaccine should NOT receive any other viral vector COVID-19 vaccine.
• history of an immediate allergic reaction of any severity within four hours (e.g., wheezing, hives) to:
  • a previous dose of the COVID-19 vaccine
  • any component of the vaccine such as:
    • polyethylene glycol (PEG) (an ingredient in mRNA vaccines)
    • polysorbate (potentially cross-reactive with PEG and an ingredient in viral vector vaccines)
• A contraindication to an mRNA vaccine is a precaution to a viral vector vaccine (and vice versa).
• Consider referrals to an allergist-immunologist with the following precautions to COVID-19 vaccination:^49,69(In the U.S. consider using the Clinical Immunization Safety Assessment [CISA] consultation by phone or online. Details can be found at https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/cisa/index.html.)
  • People with a contraindication to an mRNA COVID-19 vaccine have a precaution against viral vector COVID-19 vaccines (and vice versa).
    • If one type of COVID-19 vaccine is given (despite precautions) because of a contraindication to the other type of COVID-19 vaccine:^47,49,69
      • give the COVID-19 vaccine ≥28 days after the contraindicated COVID-19 vaccine (if one was given).
      • obtain informed consent (Canada).
• Individual COVID-19 vaccines may also have product-specific contraindications. For example, in the US the Janssen/J&J vaccine is contraindicated in patients with a history of thrombosis with thrombocytopenia following any adenovirus-vectored COVID-19 vaccine.⁸² In Canada, the Janssen/J&J vaccine is contraindicated in patients with a history of capillary leak syndrome.⁸¹ Consult product labeling for a complete list of contraindications.

How long should patients be monitored after receiving a COVID-19 vaccine?

Monitor patients receiving a COVID-19 vaccine for 30 minutes if they have:^47,49,69

• a history of severe allergic reaction (e.g., anaphylaxis) to anything.
• a history of an immediate allergic reaction of any severity to a vaccine or injectable medication.
• a contraindication to the other type of COVID-19 vaccine.

Monitor all other patients for 15 minutes after receiving a COVID-19 vaccine(including patients with a history of severe allergies to foods, pets, latex, and oral medications [excluding oral med allergies that are related to polysorbate or PEG]).^47,49,69

How does the efficacy of the available COVID-19 vaccines compare?

The CDC and Canada give preference to mRNA COVID-19 vaccines, but viral vector vaccines are still available for situations when an mRNA vaccine is contraindicated or not accessible.^69,96

There are no head-to-head data directly comparing the available COVID-19 vaccines.

• All currently available vaccines in U.S. and Canada are good vaccines.^49,69 All four vaccines have documented efficacy >70% against hospitalization for COVID-19 (data from March to August 2021) after the primary series (efficacy data after additional doses or booster doses are not yet available):^53,54,69
  • Pfizer-BioNTech/Comirnaty: 88%
  • Moderna/SpikeVax: 93%
  • Janssen/J&J: 71%
  • AstraZeneca/Vaxzevria: comparable data unavailable. Note Vaxzevria is authorized as a two-dose series with 100% efficacy with follow-up duration of up to 79 days after second dose (as of November 2020).
  • Novavax/Nuvaxovid: comparable data unavailable.  Note Nuvaxovid is authorized as a two-dose series with >90% efficacy beginning one week after the second dose.¹⁰⁷
  • Medicago/Covfenz: comparable data unavailable.  Note Covifenz is authorized as a two-dose series with >70% efficacy beginning one week after the second dose.¹⁰⁹

What are strategies to encourage patients to return for the second dose of a two-dose COVID-19 vaccine?

Stress the importance of completing the initial vaccination series with the same vaccine (COVID-19 vaccines are NOT interchangeable), if more than one dose is needed.^36,49,69

• Canadian exception:⁶⁹ an mRNA vaccine may be used for the second dose in a series that started with AstraZeneca/Vaxzevria due to the risk of vaccine-induced immune thrombotic thrombocytopenia after AstraZeneca/Vaxzevria vaccines.
• Give patients vaccine cards with product they received and second-dose reminders/date to return.
• Consider searching immunization registries if patients are not sure which vaccine they received for their first dose. U.S. subscribers can review our Immunization Registry FAQs, to learn more about registry capabilities.
• In RARE circumstances, if the initial vaccine product is not known or is no longer available, any mRNA COVID-19 vaccine may be given (ensure ≥28 days between doses).^49,69
  • If a dose of DIFFERENT mRNA vaccine is mistakenly given, instead of using the same product for the entire series, no additional doses are currently recommended.⁴⁹

Help patients understand why two doses are used for many vaccines.

• Vaccines work by teaching the body to recognize and fight a specific foreign substance (e.g., virus, bacteria).²⁶
• Think of the first dose as a primer. The body is starting from scratch to recognize and fight the virus.²⁶
• Think of the second dose as a booster. It provides the body another opportunity to learn how to respond, and to create even more memory cells against the virus.²⁶

Consider these tips to improve the likelihood patients will return for second doses:

• Make a strong recommendation to return for second doses. This can be a powerful motivator.²³
• Utilize reminder systems within your computer systems and technology (e.g., apps, texts, emails).²³
• Have patients schedule their appointment for their second dose when they receive their first dose

See our toolbox, Medication Adherence Strategies, for other adherence ideas.

What happens if the second COVID-19 vaccine dose is not given on schedule (too soon or too late)?

In the US, the recommended and optimal intervals between the first and second dose are:

• Pfizer-BioNTech/Comirnaty:  3 weeks (recommended)
• Moderna/SpikeVax:  4 weeks (recommended)
• 8 weeks may be the optimal interval between first and second doses of Pfizer or Moderna COVID-19 vaccines for some people 12 years or older, especially males between the ages of 12 and 39 years old.  However, stick with the recommended interval for patients who are moderately or severely immunocompromised, adults ≥65 years old, and patients who need rapid protection due to increased concern about community transmission or risk of severe disease.⁴⁹

In the U.S. repeat mRNA vaccine doses:⁴⁹

• are recommended if the interval between the first and second dose or second and additional dose are fewer than:
  • 17 days (Pfizer-BioNTech/Comirnaty)
  • 24 days (Moderna/SpikeVax)
• A possibility for an inadequate response exists when giving the vaccine doses too close together.
• should be given AFTER the improperly spaced dose separated by at least 21 days (Pfizer-BioNTech) or 28 days (Moderna/SpikeVax).
• are NOT needed if the second dose is given AFTER the recommended dosing interval (i.e., >21 days [Pfizer-BioNTech/Comirnaty], >28 days [Moderna/SpikeVax]).

In Canada there are not recommendations regarding repeat doses. The minimum and optimal intervals between the first and second dose are:¹⁰⁶

• Pfizer-BioNTech (Comirnaty): 19 days (minimum); 8 weeks (optimal).
  • For children between the ages of 5 to 11 years: 19 days (minimum); ≥8 weeks (optimal).⁴²
• Moderna (SpikeVax): 21 days (minimum); 8 weeks (optimal)
• AstraZeneca/Vaxzevria: 28 days (minimum); ≥8 weeks (optimal)
• Novavax/Nuvaxovid: 21 days (minimum); 8 weeks (optimal)
• Medicago/Covifenz: 21 days (minimum); 8 weeks (optimal)

What does it mean to be fully vaccinated?

People are considered fully vaccinated two weeks or more after receiving either a single dose of Janssen/J&J vaccine or the two-dose series of the other COVID-19 vaccines.^48,49

Note: People known to be immunocompromised are NOT required to receive an additional COVID-19 vaccine dose to be considered fully vaccinated (i.e., in situations where proof of vaccination is required). However, continue to emphasize preventive measures such as wearing a mask and avoiding crowds, even after an additional dose, to limit the risk of exposure.¹⁴

We still don’t know how long immunity after vaccination will last.^11,31

What are some talking points about dos and don’ts after patients are fully vaccinated?

It’s okay for fully vaccinated people (see above) with an intact immune system to resume some pre-pandemic activities:^48,78

• outdoor activities are considered low risk. Though some may choose to wear a mask in crowded settings.
• indoor activities pose low risk in areas with low or moderate transmission (some may choose to wear a mask).

Encourage patients to continue to:^48,69,78

• follow local guidance on necessary precautions.
• protect themselves and others if traveling (e.g., wear masks on planes or public transportation systems).
• watch for COVID-19 symptoms, especially if you have been around someone who is sick.

Even when fully vaccinated, continue to wear a mask indoors in areas of substantial or high COVID-19 transmission.^48,78

• Masks may still be required in some locations based on laws, regulations, or workplace guidance (e.g., hospitals, medical offices).
• Until we learn more about vaccine efficacy in people with a weakened immune system, even if fully vaccinated, wearing a mask may still be recommended. Advise patients to check with their prescriber.⁷⁸

Fully vaccinated people who come into close contact with someone with COVID-19 should:⁷⁸

• get tested for COVID-19 five to seven days after the date of exposure.
• wear a mask indoors in public until receiving a negative COVID-19 test result or for 14 days from exposure.

Explain we are still learning:^31,78

• about vaccine efficacy against COVID-19 variants.
• how effective vaccines are in people with a weakened immune system.
• how long vaccines are protective against COVID-19.

Implementation of safety precautions may change over time as we learn more about the protection provided by COVID-19 vaccination and as COVID-19 variants emerge.

Can a COVID-19 vaccine cause a
 COVID-19 infection?

No.^6,17 None of the COVID-19 vaccines that are available or are currently in development use the live SARS-CoV-2 virus.^6,17,104,109

Will COVID-19 vaccination lead to a positive COVID-19 test?

COVID-19 vaccination may lead to a positive test for COVID-19 antibodies (serology tests).⁶²

COVID-19 vaccination will NOT lead to a positive test for active COVID-19 infection (molecular or polymerase chain reaction [PCR] tests and/or antigen tests).⁴⁹

What do we know about COVID-19 vaccines during pregnancy and lactation?

Pregnant and recently pregnant patients are at higher risk for severe illness from a COVID-19 infection.¹³

In the U.S., COVID-19 vaccines, including additional doses (if immunocompromised) and booster doses, are recommended for patients who are pregnant, lactating, trying to get pregnant, or who plan to get pregnant in the future. Though no preference is specifically stated, note that mRNA COVID-19 vaccines are readily available and do not carry the rare risk of blood clots with low platelets seen with viral vector vaccines.¹³

In Canada, an mRNA vaccine series should be offered with informed consent (mRNA COVID-19 vaccines are preferred in patients who are pregnant or breastfeeding [due to rare risk of thrombosis with viral vector vaccines], but viral vector vaccines can be used if an mRNA vaccine is contraindicated or not available).⁶⁹

Preliminary data suggest that antibodies are passed to the infant (i.e., via cord blood, breast milk).⁶⁷ In fact, hospitalizations due to COVID-19 in infants less than 6 months old might be reduced in mothers completing a 2-dose mRNA COVID-19 vaccination series during pregnancy.¹⁰²

• V-SAFE data have NOT identified any safety concerns with mRNA COVID-19 for vaccinated pregnant patients or their babies.³⁰ Experts do NOT expect COVID-19 vaccines to pose risks to pregnant people, affect placental development, or cause negative pregnancy outcomes (e.g., still birth, congenital abnormalities).^6,49,66,87
• Early data suggest that pregnant/lactating people mount a similar immune response to non-pregnant people.^49,69

Reassure patients that available COVID-19 vaccines do NOT affect a person’s genetic material (DNA).^6,22,56

What do we know about COVID-19 vaccines and menstrual cycles, fertility, and puberty?

Reassure patients that there are no data (as of January 28, 2022) that any vaccine, including COVID-19 vaccines, leads to fertility problems or impacts puberty.^13,55

• Experts recommend the COVID-19 vaccine even if someone is actively trying to conceive or wishes to get pregnant in the future.¹³
• New data in humans support existing animal data that COVID-19 vaccination does not negatively impact either male or female fertility.⁴⁶

Clarify that COVID-19 vaccines are not live, and patients can’t “shed” vaccine components. Explain this means there’s no way that patients who receive a COVID-19 vaccine can impact the menstrual cycle of others around them.⁶

COVID-19 vaccination may lead to a temporary, small change in menstrual cycle length (<1 day).  Note:^97,98

• This is a longer time between bleeding, not a longer bleeding time
• This increase in menstrual cycle length is within the normal range of month-to-month variability.

Experts recommend females receive a COVID-19 vaccine despite some women reporting menstrual irregularities after receiving a COVID-19 vaccine.^73,74 Explain that:^6,73-75

• menstrual irregularities were NOT noted in early COVID-19 vaccine clinical trials.
• there is no biological mechanism explaining how COVID-19 vaccines lead to long-term menstrual irregularities.
• many things can lead to menstrual irregularities, including changes in diet, sleep, or exercise; stress; illness; etc.

What do we know about safety and efficacy of COVID-19 vaccine in patients who are immunocompromised?

We know that people who are immunocompromised are at risk for severe illness from COVID-19.³⁷

We also know that people who are immunocompromised may have a lesser response to vaccinations.⁴⁰

COVID-19 vaccines should be offered to patients with immunocompromising conditions (e.g., cancer, HIV, taking an immunosuppressant or biologics).^49,69 These are NOT live vaccines.

• Be sure to counsel these patients about the potential for a reduced immune response.⁴⁹

Reassure patients that vaccination does NOT seem to lead to autoimmune disease flares (e.g., rheumatoid arthritis, psoriasis, Crohn’s disease, multiple sclerosis).^63,95

Counsel immunocompromised patients, especially patients considered extremely vulnerable, to continue to follow recommendations to reduce risk of infection (e.g., social distancing, hand washing).⁴⁹

Who should receive an additional dose of COVID-19 vaccine AFTER completing the initial vaccination series?

An “additional dose” is a vaccine dose given to people who are not expected to build enough immunity with the initial vaccination series.⁵²

Early data indicate that an additional COVID-19 vaccine dose given to moderately or severely immunocompromised patients may improve antibody response.^42,52

• Examples of conditions or treatments that could cause a patient to be moderately or severe immunocompromised can be found at https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html (U.S.) or https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-26-covid-19-vaccine.html#t3 (Canada).^42,52 Check provincial recommendations as patient eligibility may vary among the provinces.²⁵

In the U.S., give an additional mRNA COVID-19 vaccine dose (after completing an initial two-dose mRNA vaccine series) to people who are considered moderately to severely immunocompromised.^49,52

• Moderna COVID-19 vaccines can be used for patients at least 18 years old.⁴⁹
• Pfizer-BioNTech COVID-19 vaccines can be used in patients ≥5 years old under the emergency use authorization (Comirnaty is FDA-approved for patients ≥16 years old).^49,80
• Use the same vaccine product as the initial two-dose series. If the specific mRNA vaccine used in the two-dose series is unavailable, the other mRNA COVID-19 vaccine may be used.⁴⁹
• Separate the third COVID-19 vaccine dose from the final dose of the initial two-dose series by at least 28 days.⁴⁹
• Give an additional mRNA COVID-19 vaccine dose to patients who were vaccinated with the Janssen/J&J COVID-19 vaccine at least 28 days after the Janssen/J&J dose.⁵²

In Canada, in patients who are considered moderately to severely immunomcompromised:⁴²

• Ideally, give a three-dose series (one additional dose for those who have already received two doses) of the same mRNA COVID-19 vaccine.
• Offer one additional mRNA COVID-19 vaccine dose to patients who have received one-dose viral vector vaccine or a two-dose complete series (with homologous [same vaccine for both doses] or heterologous [different vaccines to complete the series] schedule).
• Only consider an additional viral vaccine dose (requires informed consent due to lack of evidence) when other mRNA authorized COVID-19 vaccines are either contraindicated or not available.
• Separate the additional dose from final dose of the initial vaccine series by at least 28 days. Longer than 28 days may improve immune response.

Who is authorized to receive a COVID-19 booster dose in the U.S.?

A “booster dose” is a vaccine dose given to someone who responded appropriately to the initial vaccination series, to maintain immunity over time.⁵¹

Booster doses are authorized for everyone ≥18 years old (Note Pfizer/BioNTech COVID-19 vaccine booster is now authorized for kids as young as 12 years old).⁵¹

The interval between the final dose of the original COVID-19 vaccine series and the booster dose depends on which vaccine was used for the primary series. For people who received:⁵¹

• an mRNA COVID-19 vaccines (i.e., Pfizer-BioNTech, Moderna): give a booster ≥5 months after the second dose.
• a viral vector COVID-19 vaccine (Janssen/J&J): give a booster ≥2 months after the initial vaccination
• Patients who are moderately to severely immunocompromised can receive up to four COVID-19 vaccine doses if using mRNA COVID-19 vaccines.  They should receive their additional dose first (at least 28 days after their second COVID-19 vaccine dose) and their booster dose at least three months after their additional dose.⁵²  

Recommended booster doses are 0.3 mL (Pfizer-BioNTech [original dose]) or 0.25 mL (Moderna [half of the original dose]), 0.5 mL (Janssen/J&J [original dose]).^{38,49,68,70,82,101}

Can booster doses be mixed and matched, in the U.S.?

It’s okay to “mix and match” with COVID-19 vaccine booster doses.^{38,49,68,70,82,101} Preliminary data suggest giving a different COVID-19 vaccine brand as a booster dose results in similar or higher antibody levels compared to boosting with the same vaccine with similar side effects.^9,10

Base the timing of the booster dose on the original COVID-19 vaccination.^{38,49,68,70,82,101}

• five months after an original Moderna or Pfizer vaccination series.
• two months after receiving a Janssen/J&J vaccine.

Who is authorized to receive a COVID-19 booster dose in Canada?

A “booster dose” is a vaccine dose given to someone who responded appropriately to the initial vaccination series, to maintain immunity over time.⁵¹

Booster doses (given ≥6 months after completing a primary COVID-19 vaccine series) with an mRNA COVID-19 vaccine are authorized for all adults ≥18 years old taking the following into consideration:⁴²

• jurisdictional (e.g., local epidemiology, health system capacity, vaccine coverage in the population)
  AND
• individual risks (risk of waning protection, risk for severe illness, risk of transmission to people at increased risk for severe illness).
• Patients who are moderately to severely immunocompromised can receive up to four COVID-19 vaccine doses. They should receive their additional dose first (at least 28 days after their second COVID-19 vaccine dose [at least 56 days after their second dose in Ontario]) and their booster dose at least six months after their additional dose.⁹²

Consider using a viral-vector vaccine as a booster dose (with informed consent, including risk for and symptoms of thrombosis with thrombocytopenia) ONLY if an mRNA COVID-19 vaccine is contraindicated or not available.⁴²

Vaccine-specific booster doses authorized are:⁴²

• Pfizer-BioNTech (Comirnaty): 30 mcg (0.3 mL)
• Moderna (SpikeVax): 50 mcg (0.25 mL)
• AstraZeneca (Vaxzevria) and Janssen/J&J COVID-19 vaccines are not authorized as booster doses.
• Provinces may recommend different booster doses or earlier booster doses (e.g., ≥3 months after the second dose or additional dose [for immunocompromised patients]) in certain patient populations. For example, the dose of SpikeVax recommended in Ontario as the booster dose in residents of long-term care, seniors in congregate living settings, and adults ≥70 years old is the same as the original dose (100 mcg [0.5 mL]).⁹²

Can COVID-19 vaccines be given with other vaccines?

No data are available about safety or efficacy of coadministration of a COVID-19 vaccine and other vaccines.⁴⁹ Experience with other vaccines demonstrates that immunogenicity and adverse effects are generally similar when vaccines are given simultaneously as when they are given separately (e.g., separated by 14 days).⁴⁹

• COVID-19 vaccines may be given without regard to other vaccines (including the flu vaccine). There are no data regarding adverse effects with coadministration, especially with vaccines known to have increased side effects (e.g., adjuvanted vaccines).^49,69
  • When considering coadministration, consider recommended vaccine schedules, risk of vaccine-preventable disease (e.g., during an outbreak, occupational exposure), and adverse effect profile of vaccines.⁴⁹

Should someone who has COVID-19 or who was previously infected get vaccinated?

Growing evidence suggests that vaccination after COVID-19 infection provides additional protection.¹¹

Defer COVID-19 vaccination until recovery from acute COVID-19 illness and when patients meet criteria to stop isolation.⁴⁹

Guidance is unclear about giving COVID-19 vaccines to someone who is acutely ill (other than COVID-19). In general, moderate to severe illness is considered a precaution against vaccination (as vaccination side effects can make it difficult to assess management of the acute illness), while vaccination during a mild illness (with or without fever) is not a precaution.⁴³

Should someone who previously received monoclonal antibodies or convalescent plasma for COVID-19 get vaccinated?

There are no data about the use of COVID-19 vaccines in patients who received a monoclonal antibody (e.g., bamlanivimab, bamlanivimab/etesevimab [U.S. only], bebtelovimab [US only], casirivimab/imdevimab, sotrovimab, tixagevimab/cilgavimab [US only]) or convalescent plasma.^49,69,105

In the U.S.: people who received a monoclonal antibody or convalescent plasma as part of COVID-19 treatment or for pre- or post-exposure prophylaxis can receive a COVID-19 vaccine at any time.⁴⁹

In Canada, no specific timing recommendations can be made. Instead, involve an expert and make timing decisions on a case-by-case basis.⁶⁹

Authorized oral antivirals to treat COVID-19 infections include Paxlovid and molnupiravir.^94,99,100

These antivirals can be given without regard to the timing of vaccination with any available COVID-19 vaccine.  Antivirals administered any time BEFORE or AFTER a COVID-19 vaccine are NOT expected to interfere with the antibody response to vaccination.⁴⁹

Do COVID-19 vaccines contain aborted fetal cells?

Available COVID-19 vaccines do NOT contain fetal cells.^60,83-86

Fetal cells lines are used in development, production, and/or confirmatory tests of available COVID-19 and some other vaccines (e.g., hepatitis A, rubella, shingles).^83,85 For example, decades old fetal cell lines are used:^60,83-86

• to confirm that COVID-19 mRNA vaccines are taken up by cells and used as a blueprint to make a SARS-CoV-2 spike protein.
• to grow the adenovirus used in viral vector vaccines but are filtered out during the vaccine production process.

What is the role for antibody testing to assess COVID-19 immunity?

Antibody testing is NOT recommended to check immune status after COVID-19 vaccination.^49,62

• Available antibody tests are not authorized to assess immune response to vaccines.^49,62
• Reassure patients that a negative antibody test after COVID-19 vaccination does not equate to a lack of protection. Not all authorized COVID-19 antibody tests detect the IgG and IgM antibodies to the “spike protein” used in COVID-19 vaccines.⁴⁹ Antibody tests also do NOT tell us about B- or T-lymphocyte activity (e.g., B cells, T cells) which are also tools the immune system uses to mount an immune response.³⁵ This means a fully vaccinated patient could have a negative antibody test with some tests.
• Additional vaccine doses are NOT recommended based on negative COVID-19 antibody tests after vaccination.⁴⁹
• If patients get an antibody test in the middle of a COVID-19 vaccination series, encourage them to complete the series regardless of the antibody test result.⁴⁹

Antibody testing is NOT recommended as part of the decision-making process about when patients with a prior COVID-19 infection should receive a COVID-19 vaccine.⁴⁹ See the row “Should someone who has COVID-19 or who was previously infected get vaccinated?” for details on vaccination after a COVID-19 infection.

What should U.S. healthcare providers know about billing for COVID-19 vaccinations?

There will be no charge to patients for the COVID-19 vaccine. COVID-19 vaccines are currently purchased by the government. You will only be billing for the administration fee, not for the vaccine itself.^2,39

To ensure pharmacy reimbursement for the administrative fee, it is recommended to enter the following:²⁴

• Use prescription origin code 5 when a pharmacist orders the vaccine
• Quantity: use the volume to be injected for the specific vaccine being administered
• Days’ supply: “1”
• Professional services code: MA
• Ingredient cost: $0.00 or $0.01 depending on the payer
• Submission clarification code (SCC) (for vaccines requiring multiple doses):
  • “2” for the first dose of a two-dose vaccine series
  • “6” for the second dose of a two-dose vaccine series.
  • “7” for the third/additional dose for patients considered moderately to severely immunocompromised (i.e., indicates an additional dose is medically necessary, based on CDC recommendations).
  • “10” for the booster dose (some may temporarily require SCC 7 and 10 to be submitted together).

Reimbursement rates for COVID-19 vaccine administration fees are $40 per dose (effective 3/15/2021).³⁹ Medicare also authorizes an additional $35.50 per dose for at home administration to help with access.³⁹ See https://www.cms.gov/files/document/vaccine-home.pdf for details and required documentation.

COVID-19 vaccine and administrative CPT (current procedural technology) billing codes:^2,24,39

• Pfizer-BioNTech/Comirnaty: 91300 (vaccine); 0001A (administering first dose); 0002A (administering second dose); 003A (administering additional dose); 004A (administering booster dose)
• Pfizer-BioNTech/Comirnaty: ready-to-use (i.e., does not require dilution):  91305 (vaccine); 0051A (administering first dose); 0052A (administering second dose); 0053A (administering additional dose); 0054A (administering booster dose)
• Pfizer-BioNTech/Comirnaty pediatric vaccine (5 to 11 years of age):  91307 (vaccine); 0071A (administering first dose);
  0072A (administering second dose)
• Moderna/SpikeVax: 91301 (standard-dose vaccine); 0011A (administering first dose); 0012A (administering second dose); 0013A (administering additional dose)
• Moderna/SpikeVax: 91306 (lower-dose vaccine [for booster doses]); 0064A (administering booster dose)
• Janssen/J&J: 91303 (vaccine); 0031A (administering single dose); 0034A (administering booster dose)

For medicare billing information(how to submit claims including institutional, professional, and for centralized billing), go to https://www.cms.gov/medicare/covid-19/medicare-billing-covid-19-vaccine-shot-administration.

For additional pharmacist-specific reimbursement information for COVID-19 vaccine administration (e.g., steps to take to ensure eligibility for reimbursement, becoming eligible to give vaccines under Medicare, how to handle uninsured patients), go to https://www.pharmacist.com/Practice/COVID-19/Know-the-Facts.