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.
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 & JohnsonAdenoviral-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
mRNA-Based COVID-19 Vaccines Induce Robust, Persistent Immune Responses in Humans
BACKGROUND AND PURPOSE:
The mRNA-based COVID-19 vaccines are 95% effective at preventing COVID-19, but immune system dynamics induced by the vaccines are not clear
Turner et al. (Nature, 2021) examined antigen-specific B cell responses in peripheral blood and lymph nodes in individuals who received 2 doses of the Pfizer vaccine
METHODS:
Observational study
Participants
Healthy US adults who received both doses of Pfizer’s COVID-19 vaccine
Study design
Blood samples were collected at baseline (before first dose), and at weeks 3 (pre-second dose), 4, 5, 7, and 15
Fine needle aspirates of the draining axillary lymph nodes were also collected from some participants
An enzyme linked immune absorbent spot assay was used to measure antibody-secreting plasmablasts (cells that differentiate into non-dividing plasma cells [aka antibody-secreting cells])
RESULTS
41 adults
Evidence of previous SARS-CoV-2 infection: 8 participants
Aspirates collected from lymph nodes: 14 participants
Circulating IgG- and IgA-secreting plasmablasts peaked one week after the second dose and then declined | Undetectable 3 weeks later
Plasmablasts exhibited neutralizing activity against the early circulating SARS-CoV-2 strain and emerging variants
Previously infected participants had the most robust serological response
Aspirates from the draining axillary lymph nodes identified germinal center B cells that bound the SARS-CoV-2 spike protein in all participants who had received first dose
The draining lymph nodes sustained high levels of spike-binding germinal center B cells and plasmablasts for at least 12 weeks after the second dose
Spike-binding monoclonal antibodies derived from germinal center B cells mostly targeted the receptor-binding domain of the spike protein
Fewer clones did cross-react and bind to the N-terminal domain or to epitopes shared with the spike proteins of human betacoronaviruses
These cross-reactive clones had higher levels of somatic hypermutation vs those specific to SARS-CoV-2 spike protein, suggesting a memory B cell origin
CONCLUSION
mRNA-based COVID-19 vaccines induce a persistent germinal center B cell response, which leads to robust humoral immunity
The authors state
To our knowledge, this is the first study to provide direct evidence for the induction of a persistent antigen-specific germinal centre B cell response after vaccination in humans
Elicitation of high affinity and durable protective antibody responses is a hallmark of a successful humoral immune response to vaccination
By inducing robust germinal centre reactions, SARS-CoV-2 mRNA-based vaccines are on track for achieving this outcome
AstraZeneca and Pfizer Side Effects and Efficacy: Real World Data from the UK
BACKGROUND AND PURPOSE:
In phase 3 clinical trials of the Pfizer-BioNTech vaccine, injection-site pain (71 to 83%), fatigue (34 to 47%), and headache (25 to 42%) were commonly seen
Menni et al. (The Lancet Infectious Diseases, 2021) investigate the safety and effectiveness of the Pfizer and AstraZeneca vaccines in a UK community setting
METHODS:
Prospective observational study
Data source
COVID Symptom Study app data
Between Dec 8 through March 10, 2021
Population
General UK population
Exposure
One or two doses of the Pfizer -BioNTech vaccine
One dose of the AstraZeneca vaccine
Unvaccinated controls
Study design
All analyses were adjusted by
Age (≤55 years vs >55 years)
Sex
Health-care worker status (binary variable)
Obesity (BMI <30 kg/m2 vs ≥30 kg/m2)
Comorbidities (binary variable, with or without comorbidities)
Primary outcome
Proportion and probability of self-reported systemic and local side effects within 8 days of vaccination
Secondary outcome
SARS-CoV-2 infection rates in vaccinated individuals
RESULTS:
627,383 vaccinated individuals
At least one dose of Pfizer-BioNTech: 282,103 individuals | Two doses of Pfizer-BioNTech: 28,207 individuals
One dose of AstraZeneca: 345,280 individuals
Systemic Side Effects
Report rates of systemic side effects after vaccination
After first dose of Pfizer-BioNTech: 13.5% | After second dose of Pfizer-BioNTech: 22.0%
After first dose of AstraZeneca: 33.7%
Most common systemic side effects
Fatigue and headache
Usually within first 24 hours after vaccination | Lasted a mean of 1.01 days
Systemic side effects were more common among those with a history of previous SARS-CoV-2 infection
After first dose of Pfizer-BioNTech: 2.9 times more likely
After first dose of AstraZeneca: 1.6 times more likely
Adverse systemic events were more common in
Women vs men: 16.2% vs 9.3% after first dose of Pfizer-BioNTech (OR 1.89 [95% CI, 1.85 to 1.94]; p<0·0001) and similarly after first dose of AstraZeneca
≤55 years vs >55 years: 20.7% vs 10.6% after first dose of Pfizer-BioNTech (OR 2.19 [95% CI, 2.14 to 2.24]; p<0.0001) and similarly after first dose of AstraZeneca
Similar pattern in women and younger individuals were also noted for local side effects
Local Side Effects
Most common local side effects
Tenderness and local pain around the injection site
Usually on the day after injection | Lasted a mean of 1.02 days
Local side effects after vaccination
After first dose of Pfizer-BioNTech: 71.9% | After second dose of Pfizer-BioNTech: 68.5%
After first dose of AstraZeneca: 58.7%
Local side effects were also higher in individuals previously infected with SARS-CoV-2
After first dose of Pfizer-BioNTech: 1.2 times more likely to experience side effects
After first dose of AstraZeneca: 1.4 times more likely
Vaccine Effectiveness
SARS-CoV-2 positive tests
Vaccinated: 3% (3106 infections per 103,622 vaccinated)
Unvaccinated: 11% (50,340 infections per 464,356 unvaccinated)
Significant reductions in infection risk were seen starting at 12 days after the first dose and increased over time
At 21 to 44 days
Pfizer-BioNTech: 69% (95% CI 66 to 72)
AstraZeneca: 60% (95% CI 49 to 68)
At 45 to 59 days
Pfizer-BioNTech: 72% (95% CI 63 to 79)
CONCLUSION:
Systematic and local side effects with Pfizer and AstraZeneca COVID-19 vaccination were more common in women, individuals ≤55 years, and those with previous COVID-19 infection
A reduction in infection risk was observed starting 12 days after the first dose for both vaccines
The authors conclude
Localised and systemic side effects after vaccination are less common in a real-world community setting than reported in phase 3 trials, mostly minor in severity, and self-limiting
Our data will enable prediction of side-effects based on age, sex, and past COVID-19 status to help update guidance to health professionals to reassure the population about the safety of vaccines
Johnson & Johnson COVID-19 Vaccine: Safety and Efficacy Data from the Phase 3 Trial
BACKGROUND AND PURPOSE:
Ad26.COV2.S, known as the Johnson & Johnson COVID-19 vaccine in the US, is a viral vector vaccine that uses an adenovirus vector encoding SARS-CoV-2 spike protein
Sadoff et al. (NEJM, 2021) report the primary analyses of an ongoing phase 3 trial to evaluate the safety and efficacy of a single dose for prevention of COVID-19 and SARS-CoV-2 infection in adults
ASH Guidelines: Diagnosis and Management of COVID-19 Vaccine-Induced Thrombosis with Thrombocytopenia
SUMMARY:
Although very rare, thrombosis with thrombocytopenia syndrome (TTS) has been associated with AD26.COV2.S (J&J) vaccine in the US and similar events have been documented outside the US with use of the CHaDOx1 nCov-19 (AstraZeneca) vaccine. This syndrome has been referred to by alternate names in the literature, including vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) or ‘vaccine-induced immune thrombotic thrombocytopenia (VITT)’. TTS is being used by the FDA and CDC. The American Society of Hematology has provided guidance on diagnosis and when to refer.
TTS Diagnostic Criteria
All 4 criteria must be met
J&J or AstraZeneca vaccine within 4 to 30 days
Venous or arterial thrombosis (often cerebral or abdominal)
Note: In early stage of TTS, thrombosis may be present prior to platelet count decrease
Clinical Findings
Severe headache
Visual changes
Abdominal pain
Nausea and vomiting
Back pain
Shortness of breath
Leg pain or swelling
Petechiae, easy bruising, or bleeding
Work-Up
Labs
CBC with platelet count and peripheral smear
Mean platelet count in published reports: 20,000/μL | There is a range from profound to mild
D-dimers: Most patients have significantly elevated levels
Fibrinogen: Some patients have low levels
PF4-heparin ELISA: almost all cases reported have positive assays | Most will have optical density >2.0 to 3.0
Note: Do not use non-ELISA rapid immunoassays for HIT | Non-ELISA tests are not sufficiently sensitive nor specific for TTS
Imaging for Thrombosis
Imaging based on symptoms
Focus on cerebral sinus venous thrombosis (CSVT) with use of CT or MRI venogram
Patients may also have splanchnic thrombosis, pulmonary emboli, and/or DVT
Treatment
IVIG 1 g/kg daily for two days
Non-heparin anticoagulation
Parenteral direct thrombin inhibitors (argatroban or bivalrudin if aPTT is normal) or
Direct oral anticoagulants without lead-in heparin phase or
Fondaparinux or
Danaparoid
When to Treat
While waiting for PF4 ELISA
Begin IV immune immunoglobin and nonheparin anticoagulation if there is clinical evidence of serious thrombosis AND ≥1 of the following
Positive imaging
Low platelets
If PF4 ELISA returns negative and there is no thrombocytopenia, TTS is ruled out
Treat for venous thromboembolism using standard protocols
KEY POINTS:
TTS is suspected
Obtain immediate CBC with platelet count and imaging for thrombosis based on symptoms
If thrombosis and/or thrombocytopenia is present, referral to hematologist with expertise in hemostasis is recommended
Do not use non-ELISA rapid immunoassays for HIT
Avoid heparin until TTS ruled out or other reasonable diagnosis has been established
In addition
If thrombocytopenia but no thrombosis and negative PF4 ELISA, likely ITP
Microangiopathy with red cell fragmentation and hemolysis have not been features of reported cases, thus distinguishing this syndrome from TTP/HUS is straightforward
Avoid platelet transfusions unless other treatments have been initiated AND life-threatening bleeding or imminent surgery
Consider referral to tertiary care center if TTS is confirmed
The clinical trials for mRNA-based COVID-19 vaccines did not include any pregnant women, so safety data in this group was initially limited
However, many pregnant women in the general population have since received these vaccines, providing a cohort in which to assess safety data
Shimabukuro et al. (NEJM, 2021) reported preliminary findings regarding mRNA COVID-19 vaccine safety in pregnant persons from three U.S. vaccine safety monitoring systems
METHODS:
Setting
United States
Data from December 14, 2020, to February 28, 2021
Data sources
The “V-safe after vaccination health checker” surveillance system
The V-safe pregnancy registry | Telephone-based survey collects detailed information
The Vaccine Adverse Event Reporting System (VAERS)
Primary outcomes
Non–pregnancy-specific adverse events
Pregnancy- and neonatal-specific adverse events
Note: Pregnancy and neonatal outcomes were derived from patients who enrolled in the registry
RESULTS:
35,691 v-safe participants self-identified as pregnant
Majority of the participants were
Between 25 to 34 years of age | Non-Hispanic White (approximately 75%)
3958 participants were enrolled in the registry
Vaccine-related side effects (V-safe)
Injection-site pain was reported more frequently among pregnant women than among nonpregnant women
The following were reported less frequently among pregnant women
Headache
Myalgia
Chills
Fever
Pregnancy Outcomes
827 participants completed pregnancy
Live birth: 86.1%
Spontaneous abortion: 12.6%
Stillbirth (0.1%)
Other outcomes (induced abortion and ectopic pregnancy): 1.2%
Neonatal Outcomes
Preterm birth: 9.4%
Small for gestational age: 3.2%
There were no neonatal deaths
Adverse Events (VAERS)
221 reports
Nonpregnant related: 70.1%
Pregnancy related: 29.9%
Most frequently reported pregnancy-related adverse events
Spontaneous abortion (37 first trimester, 2 second trimester, 7 unknown or not reported)
No congenital anomalies (EUA reporting requirement)
CONCLUSION:
While not directly comparable, the proportions of adverse outcomes in vaccinated women were similar to those reported in studies involving pregnant women before the pandemic
Further longitudinal study is important, especially in women vaccinated in the first trimester
The authors conclude that
Early data from the v-safe surveillance system, the v-safe pregnancy registry, and the VAERS do not indicate any obvious safety signals with respect to pregnancy or neonatal outcomes associated with Covid-19 vaccination in the third trimester of pregnancy
Does COVID-19 Vaccination in Breastfeeding Women Produce Detectable Levels of Antibodies in Breast Milk?
BACKGROUND AND PURPOSE:
Breastfeeding women were not included in COVID-19 vaccine trials, so there are limited data on vaccine-related safety in this group
Perl et al. (JAMA, 2021) investigated whether maternal immunization led to detection of SARS-CoV-2 antibodies in breast milk
METHODS:
Prospective cohort study
Setting
Israel, between December 23, 2020, and January 15, 2021
Participants
Breastfeeding women (exclusive or partial)
Elected to be vaccinated
Exposure
All participants fully vaccinated with Pfizer-BioNTech vaccine
Study design
Participants were recruited through advertisements and social media
Breast milk samples were collected
Before administration of the vaccine
Once weekly for 6 weeks starting at week 2 after the first dose
IgG and IgA antibody levels were assessed
Weekly questionnaires coupled to breast milk collection asked participants for information about interim well-being and vaccine-related adverse events
Primary outcomes
Presence and levels of SARS-CoV-2 antibodies in breast milk
RESULTS:
84 women | 504 breast milk samples
Women: mean age 34 years
Infants: mean age 10.32 months
Mean levels of SARS-CoV-2- IgA antibodies in breast milk increased rapidly and remained elevated throughout follow-up
2 weeks after first dose: 61.8% of samples tested positive
4 weeks after first dose: 86.1% of samples tested positive
6 weeks after first dose: 65.7% of samples tested positive
IgG antibodies remained low for the first 3 weeks, with an increase at week 4, which remained high throughout follow-up
4 weeks after first dose: 91.7% of samples tested positive (P=0.004)
5 and 6 weeks after first dose: 97% of samples tested positive
Adverse events were experienced by a majority of women, but were generally mild, with local pain being the most common complaint
Reported events after the first dose: 55.9% of women
Reported events after the second dose: 61.9% of women
No mother or infant experienced any serious vaccine-related adverse event
Four infants developed a fever after maternal vaccination
CONCLUSION:
Both IgA and IgG SARS-CoV-2 antibodies were detected in breast milk of vaccinated mothers
IgA presence was evident as early as 2 weeks after the first vaccine dose
IgG spiked 4 weeks after the first dose
IgA and IgG levels remained elevated throughout the follow-up period
No major adverse events in mothers or infants were reported
The authors conclude
Antibodies found in breast milk of these women showed strong neutralizing effects, suggesting a potential protective effect against infection in the infant
Potential Pathology Behind AstraZeneca COVID-19 Vaccination and Blood Clots
BACKGROUND AND PURPOSE:
Schultz et al. (NEJM, 2021) describes 5 cases of severe thrombosis and thrombocytopenia following vaccination with the ChAdOx1 (AstraZeneca) COVID-19 vaccine
METHODS:
Case reports
Setting
Oslo University Hospital, Norway
Cases included
5 healthcare workers
32 to 54 years old
Study design
Serum antibodies tested (ELISA)
Platelet factor 4 (PF4)-polyanion complexes
SARS-CoV-2 spike and nucleocapsid proteins
RESULTS:
4 patients had severe cerebral venous thrombosis with intracranial hemorrhage | Fatal in 3 patients
At time of admission
Levels of D-dimer were elevated in all patients
Screening for thrombophilia with proteins C and S and antithrombin was negative
Platelet immunologic testing
All five patients had high levels of IgG antibodies to PF4–polyanion complexes
Platelets in serum from Patients 1, 3, 4, and 5 were clearly activated in the absence of added heparin
All patients were negative for SARS-CoV-2 antibodies, suggesting previous infection was unlikely
CONCLUSION:
5 individuals developed severe venous thromboembolism in unusual sites and concomitant thrombocytopenia 7 to 10 days after vaccination (AstraZeneca)
All 5 patients had a high level of antibodies to PF4–polyanion complexes
The authors suggest
…that these cases represent a vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia (VITT)
The Value of Vaccination for Those Previously Infected with SARS-CoV-2
BACKGROUND AND PURPOSE:
BNT162b2 (Pfizer/BioNTech) COVID-19 vaccine was shown to be 95% effective at preventing COVID-19
Several COVID-19 variants have been detected in recent months
South Africa variant: B.1.351
UK variant: B.1.1.7
Brazil variant: P.1
Lustig et al. (NEJM Correspondence, 2021) investigated whether one dose of the BNT162b2 vaccine would increase neutralizing activity against the B.1.1.7, B.1.351, and P.1 variants in people previously infected with SARS-CoV-2
METHODS:
Microneutralization assay
Population
Healthcare workers
Previously infected with the original SARS-CoV-2
Study design
All participants were given a single dose of the BNT162b2 vaccine
Serum samples were obtained
1 to 12 weeks after natural infection
Immediately before vaccination
1 to 2 weeks after vaccination
RESULTS:
18 serum samples from 6 healthcare workers
The sample obtained at the first time point (1 to 12 weeks after infection)
Had neutralizing activity against
The original virus: geometric mean titer 456
B.1.1.7 (UK): 256
P.1 (Brazil): 71
Had no neutralizing activity against
B.1.351 (South Africa): geometric mean titer 8
Immediately before BNT162b2 vaccination, titers were lower against all virus variants
Original virus: geometric mean titer 81
B.1.1.7 (UK): 40
P.1 (Brazil): 36
B.1.351 (South Africa): 7
1 to 2 weeks after vaccination, titers were high against all virus variants
Original virus: geometric mean titer 9195
B.1.1.7 (UK): 8192
P.1 (Brazil): 2896
B.1.351 (South Africa): 1625
CONCLUSION:
After one dose of the BNT162b2, people who had previously been infected with the original SARS-CoV-2 showed high neutralizing activity against the UK, South Africa and Brazil variants
The authors conclude
This highlights the importance of vaccination even in previously infected patients, given the added benefit of an increased antibody response to the variants tested
COVID-19 mRNA Vaccine Effectiveness in the Real World Including in Those Partially Immunized
BACKGROUND AND PURPOSE:
Both mRNA COVID-19 vaccines (Moderna and Pfizer/BioNTech) have been shown to be effective at preventing symptomatic COVID-19 in phase III trials
Thompson et al. (CDCMMWR, 2021) quantified SARS-CoV-2 infections among vaccinated, partially-vaccinated, and non-vaccinated essential personnel every week for 12 weeks
METHODS:
Prospective cohort study (December 14, 2020 to March 13, 2021)
Setting
Eight locations in the US
Participants
Health care personnel | First responders | Other essential and frontline workers
No previous laboratory documentation of SARS-CoV-2 infection
Exposure
Vaccination status
Fully immunized (≥14 days after second dose)
Partially immunized (≥14 days after first dose and before second dose)
Unvaccinated
Study design
The CDC tested for SARS-CoV-2 infections
Every week regardless of symptom status and
At the onset of symptoms consistent with COVID-19–associated illness
SARS-CoV-2 infections were confirmed by RT-PCR
Statistical analysis
Authors accounted for time-varying vaccination status
Results adjusted for site
RESULTS:
3,950 participants with no previous SARS-CoV-2 infection
Fully immunized: 62.8%
Partially immunized: 12.1%
SARS-CoV-2 infection
Unvaccinated: 1.38 infections per 1,000 person-days
Fully immunized: 0.04 infections per 1,000 person-days
Partially immunized: 0.19 infections per 1,000 person-days
Estimated mRNA vaccine effectiveness for prevention of infection
Full immunization: 90%
Partial immunization: 80%
CONCLUSION:
Both mRNA COVID-19 vaccines are effective at preventing infection, both symptomatic and asymptomatic, in essential personnel in real world conditions
The authors conclude
These interim vaccine effectiveness findings for both Pfizer-BioNTech’s and Moderna’s mRNA vaccines in real-world conditions complement and expand upon the vaccine effectiveness estimates from other recent studies and demonstrate that current vaccination efforts are resulting in substantial preventive benefits among working-age adults
They reinforce CDC’s recommendation of full 2-dose immunization with mRNA vaccines
COVID-19 vaccination is recommended for all eligible persons
Vaccines in Pregnant and Lactating Women: Is Immune Response Similar to that of Non-Pregnant Patients?
BACKGROUND AND PURPOSE:
Gray et al. (AJOG, 2021) evaluated the immunogenicity (ability to provoke an immune response) and reactogenicity (ability to provoke expected adverse reactions) of COVID-19 mRNA vaccination in pregnant and lactating women vs non-pregnant controls
METHODS:
Prospective cohort study
Participants (≥18 years)
Pregnant or nursing
Non-pregnant and of reproductive age
Exposure
COVID-19 vaccine (Pfizer or Moderna mRNA vaccine)
Study design
SARS-CoV-2 IgG, IgA and IgM were quantified in sera and breastmilk
Timepoints: Baseline | Second vaccine dose | 2 to 6 weeks post second vaccine | Delivery
Titers compared to those of pregnant women 4 to 12 weeks following natural infection (ELISA platform used)
Neutralizing antibody titers were evaluated for a participant subset who delivered
Post-vaccination symptoms were assessed via questionnaire
Differences between groups was assessed, including using statistical tools to account for multiple sampling
RESULTS:
131 vaccine recipients | Cord blood obtained from 10 deliveries
Pregnant: 84
Lactating: 31
Non-pregnant: 16
Compared to non-pregnant women, pregnant and lactating women had similar vaccine-induced antibody titers (p=0.24)
Pregnant: Median (IQR) 5.59 (4.68 to 5.89]
Lactating: Median (IQR) 5.74 (5.06 to 6.22)
Non-pregnant: Median (IQR) 5.62 (4.77 to 5.98)
All vaccine-induced titers were significantly higher than those induced by natural SARS-CoV-2 infection during pregnancy (p<0.0001)
Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples
IgG breast milk levels rose concurrently with maternal serum levels
While neutralizing antibody titers were lower in umbilical cord vs maternal sera, the difference was not statistically significance (p=0.05)
Umbilical cord sera: median (IQR) 52.3 (11.7 to 69.6)
Maternal sera: 104.7 (61.2 to 188.2)
Second vaccine dose increased SARS-CoV-2-specific IgG but not IgA, such that IgG was the dominant serum antibody for all groups by 2 weeks post-second vaccine
Reactogenicity was similar across pregnant, lactating and non-pregnant groups
CONCLUSION:
Pregnant and lactating women who received either of the COVID-19 mRNA vaccines experienced robust vaccine-induced immunity
Immunogenicity and reactogenicity in pregnancy were similar to that seen in non-pregnant women
The vaccine-induced immunity response was significantly greater than the immune response caused by natural SARS-CoV-2 infection
Immune transfer to neonates could occur via breastmilk or placenta
While the authors are clear that this study does not address possible fetal risks, they conclude
While the absolute risk of severe COVID-19 is low in pregnant women, pregnancy is a risk factor for severe disease
These data provide a compelling argument that COVID-19 mRNA vaccines induce similar humoral immunity in pregnant and lactating women as in the non-pregnant population
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This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
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presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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