SUMMARY:

The CDC currently recommends COVID-19 vaccination for individuals 6 months and older in the United States for the prevention of coronavirus disease 2019 (COVID-19) including booster dose. Vaccination during pregnancy and lactation period is encouraged to mitigate the significant risks associated with COVID.

• Counseling Points
• Maternal and Obstetric Risk
• Vaccine Mechanism
• Primary Series Dosing
• Booster
• Key Points

Counseling Points

• The SMFM document refers clinicians to the CDC recommendations (links can be found in ‘Learn More – Primary Sources’ below)
• CDC recognizes pregnant women are at risk for severe health effects from COVID-19 and recommends COVID-19 vaccination during pregnancy
  • While a conversation with a healthcare provider may be of benefit, it is not a requirement prior to vaccination
• Counseling should include the following elements
  • Available data on vaccine safety
  • Discussion about limited data regarding fetal risk
  • Pregnant patients have higher risk of moderate to severe disease
  • Level of COVID-19 community transmission

Maternal and Obstetric Risk 

• With symptomatic COVID-19, pregnancy is an independent risk factor compared to symptomatic non-pregnant patients for
  • ICU admission: 3-fold increase
  • Mechanical ventilation
  • ECMO: 2 to 4 fold increase
  • Death: 1.7 fold increase
  • May increase preterm birth and stillbirth
• Other risk factors for severe COVID-19 disease include
  • Cancer | Chronic kidney disease | COPD | Heart conditions | Immunocompromised state | Sickle cell disease | Smoking
• Hispanic or Latinx and Black patients are disproportionally affected by higher prevalence of COVID-19
  • More severe maternal morbidity | Higher risk of death

Vaccine Mechanism

• Three COVID-19 vaccines are currently available in US | None are live vaccines

mRNA Vaccines (Pfizer | Moderna)

• Contain mRNA for SARS-CoV-2 spike S protein
  • Pfizer-BioNTech BNT162b2
  • Moderna mRNA 1273 vaccines
• Two-dose vaccine (Pfizer 3 weeks apart; Moderna 4 weeks apart)

Protein Subunit Vaccine (Novavax) 

• Contains combination of spike proteins
• Also includes an adjuvant that improves immune response
• Similar technology to that used for HepB and HPV
• Two-dose vaccine (3 to 8 weeks apart)

Adenoviral-Vector Vaccine (Janssen Biotech Ad26.COV2.S; Pharmaceutical company of Johnson & Johnson)

• One-dose vaccine
• Adenovirus carries the gene for the coronavirus spike S protein, which is then produced by the host cell
  • The presence of spike protein on the host cell’s membrane will induce an immunogenic response

Note: Due to increased risk for thrombosis with thrombocytopenia syndrome (TTS), the FDA has limited the authorized use of the Janssen COVID-19 Vaccine to (1) individuals 18 years of age and older for whom other authorized or approved COVID-19 vaccines are not accessible or clinically appropriate, and (2) to individuals 18 years of age and older who elect to receive the Janssen COVID-19 Vaccine because they would otherwise not receive a COVID-19 vaccine

Considerations for Administration

• Pregnancy test prior to vaccination is not recommended
• No need to delay pregnancy following vaccine administration
• No trimester-specific indications at this time

Efficacy

mRNA Vaccines

• Optimal efficacy 1 to 2 weeks after second dose
• Pfizer-BioNTech: 95.0% (95% CI, 90.3% to 97.6%)
• Moderna: 94.1% (95% CI, 89.3% to 96.8%)

Novavax

• 89.7% (95% CI, 80.2% to 94.6%)

Johnson & Johnson Adenoviral-Vector Vaccine (Janssen Biotech)

• 1 time dose
• 72% effective at preventing moderate to severe disease
• 85% effective at preventing severe disease
• 100% effective at preventing COVID-19–related hospitalization and death 28 days after vaccination

Primary Series Dosing

• Pfizer-BioNTech: 2-dose primary series
  • 5 to 11 years: 10 µg dose | 3 weeks apart
  • ≥12 years: 30 µg dose | 3 to 8 weeks apart
• Moderna: 2-dose primary series
  • 6 to 11 years: 50 µg | 4 to 8 weeks apart
  • ≥12 years: 100 µg | 4 to 8 weeks apart
• Novavax: 2-dose primary series
  • ≥12 years: 5 µg rS and 50 µg of Matrix-M™ adjuvant
• Janssen: Single dose primary series
  • ≥18 years: 5×10¹⁰ viral particles

Primary Series for Children From 6 Months Through 5 Years of Age

• Pfizer (6 months through 4 years)
  • 3 primary doses are recommended
  • Monovalent Pfizer-BioNTech vaccine is administered for the first and second doses, followed by 1 bivalent Pfizer-BioNTech vaccine as the third primary series dose, at least 8 weeks after the second monovalent primary series dose
• Moderna (6 months through 5 years)
  • 2 primary doses are recommended
  • 25 µg per dose (1/4 adult dose)
  • Interval between 1st and 2nd dose: 4 to 8 weeks

Note: Spacing between first and second can be up to 8 weeks with both Pfizer and Moderna vaccines (CDC) | Although absolute risk for myocarditis associated with mRNA vaccine is small, some studies suggest that among adolescents and adults, the risk for myocarditis may be reduced and peak antibody responses and vaccine effectiveness may be increased with an interval longer than 4 weeks | Original interval is still recommended for “people who are moderately or severely immunocompromised; adults ages 65 years and older; and others who need rapid protection due to increased concern about community transmission or risk of severe disease”

COVID-19 Vaccines for People who are Moderately or Severely Immunocompromised

• CDC has specific recommendations for COVID vaccine schedules for individuals who are moderately or severely immunocompromised | See ‘Learn More – Primary Sources’ for the most current information for the most current schedules
• Children ages 5 through 11 years
  • Should receive a primary series of 3 doses of Pfizer-BioNTech COVID-19 vaccine
  • Additional booster not recommended at this time
• People ≥12 years
  • Should receive a total of 4 doses of mRNA COVID-19 vaccine to stay up to date
  • The 4 doses include a primary series of 3 doses of Pfizer-BioNTech or Moderna COVID-19 vaccine plus 1 booster of Pfizer-BioNTech or Moderna COVID-19 vaccine (4th dose)
  • Only Pfizer-BioNTech COVID-19 vaccine is available for teens ages 12 to 17 years
• Moderate or severe immunocompromising conditions that include (but 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/mm³, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV)
  • Treatments: 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 | Other biologic agents that are immunosuppressive or immunomodulatory

Booster (CDC)

• Children ages 6 months to 4 years who complete a Moderna primary series
  • To receive 1 bivalent Moderna booster dose at least 2 months after completion of the primary series
• Children age 5 years who complete a Moderna primary series
  • May receive either the previously authorized bivalent Pfizer-BioNTech booster dose or the newly authorized bivalent Moderna booster dose at least 2 months after completion of the Moderna primary series
• Children ages 6 months to 4 years who have received a Pfizer-BioNTech 3-dose primary series, including children who previously received a 3-dose monovalent Pfizer-BioNTech primary series
  • A booster dose is not authorized for children in this age group
• Everyone ages 5 years and older who is eligible is recommended to receive 1 bivalent mRNA booster dose after completion of a monovalent primary series or previously received monovalent booster dose(s)
  • Bivalent vaccines have replaced old monovalent formulations for booster doses, though they remain the mainstay of initial vaccination
  • Omicron BA.4 and BA.5 spike proteins were added to the original vaccine
  • The booster is a bivalent vaccine, since it targets both omicron and the original SARS-Cov2 strain
• 5 to 17 years
  • Recommendations for use of a bivalent Moderna booster dose in people ages 6 to 17 years
  • Recommendations for use of a bivalent Pfizer-BioNTech booster dose in people ages 5 to 17 years
• Adults ≥18 years
  • Pfizer or Moderna COVID vaccine ≥2 months after completion of primary mRNA vaccine series
  • Moderately or severely immunocompromised: Pfizer or Moderna COVID vaccine bivalent ≥2 months after the final dose in the primary series
• Pregnancy and bivalent boosters
  • ACOG recommends that those who are pregnant or are within the 6 week postpartum period receive a bivalent mRNA COVID-19 vaccine booster dose following the completion of their last COVID-19 primary vaccine dose or monovalent booster

Note: Considered ‘up to date’ immediately after getting 1st booster

Fetal Considerations

• Limited data | Preclinical studies have been reassuring
• mRNA vaccines
  • Available data suggests low risk
  • Rapid degradation (approximately 10 to 20 days)
  • Does not enter the cell’s nucleus or become integrated into the DNA; therefore, “no risk of genetic modification to people receiving the vaccine”
• Adenovector vaccines
  • Available data suggests low risk
  • Viral DNA is not integrated into the host’s DNA
  • Other adenovirus vector vaccines (Ebola, HIV, and RSV) showed no adverse pregnancy outcomes
• Maternal antibodies cross the placenta | May provide neonatal protection

CDC Adverse Event Data

• V-safe
  • CDC “smartphone-based tool that uses text messaging and web surveys to provide personalized health check-ins” that can be used by an individual to report side effects following COVID-19 vaccination
  • Women continue to enroll in CDC’s v-safe COVID-19 Vaccine Pregnancy Registry | No serious safety signals have been identified thus far (see ‘Learn More – Primary Resources’ and ‘Related ObG Topics’ below)
  • Reactogenicity (expected inflammatory response to vaccination) and adverse events did not raise any concerns regarding increased risk for maternal or neonatal complications
• Vaccine Adverse Event Reporting (VAERS)
  • Miscarriage was highest pregnancy related adverse event
  • Rates around 15% in keeping with normal background
• General findings from current available data
  • No pattern suggesting of safety issue  
  • Vaccine reactions are usually mild to moderate
    • Occur within the first 3 days and  resolve within 1 to 2 days
    • Most often symptoms occur after second dose
    • Acetaminophen can be used to treat fever
  • Allergic reactions: rare (2.5 to 4.7 per million)

Lactating Persons

• Vaccination is recommended for lactating persons
• Counseling should provide balance with respect to lack of data vs the patients’ individual risk for infection and severe disease
• Although there is a lack of data “the theoretical risks regarding the safety of vaccinating lactating people do not outweigh the potential benefits of the vaccine”

Antibody Titers in Pregnancy

• Studies have demonstrated vaccine-induced antibody titers to be similar in pregnant women compared to nonpregnant women
• Transfer of antibodies to newborns following maternal vaccination may confer neonatal protection
  • Vaccine-induced IgG is transferred to the neonate
  • Higher umbilical cord blood titers are associated with longer time intervals from vaccination
  • Second vaccine dose increases cord blood IgG levels

KEY POINTS:

• The COVID-19 vaccine should be offered to all eligible individuals 6 months and older including pregnant and lactating patients
  • ACOG recommends that “all people, including pregnant people receive a bivalent mRNA COVID-19 vaccine booster dose following the completion of their last COVID-19 primary vaccine dose or monovalent booster”
• Providers should discuss individual risks and benefits of the vaccine during pregnancy
• Safety profile from the CDC Adverse Event Monitoring site shows no increased risk of worse pregnancy outcomes post-vaccination with more data to be published
• COVID-19 vaccines and other vaccines may now be administered without regard to timing

Learn More – Primary Resources

SMFM: Provider Considerations for Engaging in COVID-19 Vaccine Counseling With Pregnant and Lactating Patients

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

CDC: COVID-19 Vaccine Booster Shots

ACOG: COVID-19 Vaccination Considerations for Obstetric–Gynecologic Care

CDCD: COVID-19 Vaccines for People who are Moderately or Severely Immunocompromised

CDC: v-safe COVID-19 Vaccine Pregnancy Registry

CDC: COVID-19 Vaccine Monitoring Systems for Pregnant People

CDC: Vaccine Adverse Event Reporting System (VAERS)

Coronavirus (COVID-19) Update: FDA Limits Use of Janssen COVID-19 Vaccine to Certain Individuals

Related ObG Topics: