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Guidance on COVID-19 Vaccine Including Pregnancy


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). Vaccination during pregnancy and lactation period is encouraged to mitigate the significant risks associated with COVID. 


Updated mRNA Vaccine: Pfizer and Moderna

  • Monovalent (single) component that corresponds to the Omicron variant XBB.1.5  
  • ≥5 years regardless of previous vaccination 
    • Single dose of an updated mRNA COVID-19 vaccine at least 2 months since the last dose of any COVID-19 vaccine 
  • 6 months through 4 years who have previously been vaccinated against COVID-19  
    • 1 or 2 doses of an updated mRNA COVID-19 vaccine (timing and number of doses to administer depends on the previous COVID-19 vaccine received)  
  • Unvaccinated individuals 6 months through 4 years of age  
    • 3 doses of the updated authorized Pfizer-BioNTech COVID-19 Vaccine or 2 doses of the updated authorized Moderna COVID-19 Vaccine 

Updated Novavax Vaccine

  • An updated Novavax Vaccine has also been approved for ≥12 years
    • If patient received any vaccine: Administer ≥2months later
    • If not previously vaccinated: 2 doses 3 weeks apart

Vaccine Mechanism 

mRNA Vaccines (Pfizer | Moderna) 

  • Contain mRNA for SARS-CoV-2 spike S protein 

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 

Pregnancy Counseling Points  

  • SMFM endorses the CDC recommendations and supports the use of the updated vaccine in pregnancy and among those breastfeeding (see ‘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 

Considerations for Administration During Pregnancy  

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

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    

  • Healthcare providers are required to report certain adverse events following COVID-19 vaccination to the Vaccine Adverse Event Reporting System (VAERS)
  • “Anyone can submit a report to VAERS – healthcare professionals, vaccine manufacturers, and the general public. VAERS welcomes all reports, regardless of seriousness, and regardless of how likely the vaccine may have been to have caused the adverse event.”


  • 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 


  • The COVID-19 vaccine should be offered to all eligible individuals 6 months and older including pregnant and lactating patients 
  • 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 

SMFM: COVID_Vaccine_2023

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

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

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

CDC: Vaccine Adverse Event Reporting System (VAERS) 

mRNA-Based COVID-19 Vaccines Induce Robust, Persistent Immune Responses in Humans


  • 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 


  • 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]) 


  • 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 


  • 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 

Learn More – Primary Sources: 

SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses 

AstraZeneca and Pfizer Side Effects and Efficacy: Real World Data from the UK


  • 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


  • 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


  • 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)


  • 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

Learn More – Primary Sources:

Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study

Johnson & Johnson COVID-19 Vaccine: Safety and Efficacy Data from the Phase 3 Trial


  • 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


  • International, randomized, double-blind, placebo-controlled, phase 3 trial
  • Participants
    • Adults aged 18 to 59 years of age
    • Seronegative or unknown serostatus at the start of the study (‘per protocol’ patients)
  • Intervention
    • Single dose
    • Placebo
  • Primary outcomes
    • Vaccine efficacy against moderate to severe/critical COVID-19
      • Onset at least 14 days after vaccination
      • Onset at least 28 days after vaccination
    • Safety


  • 19,630 received vaccine | 19,691 received placebo
  • Vaccine protected against moderate to severe/critical Covid-19
    • Cases with onset at least 14 days after administration
      • Vaccine group: 116 cases
      • Placebo group: 348 cases
      • Efficacy 66.9% (adjusted 95% CI, 59.0 to 73.4)
    • Cases with onset at least 28 days after administration
      • Vaccine group: 66 cases
      • Placebo group: 193 cases
      • Efficacy 66.1% (adjusted 95% CI, 55.0 to 74.8)
  • Vaccine efficacy was higher against severe–critical Covid-19
    • Severe cases with onset at least 14 days after administration
      • Efficacy 76.7% (adjusted 95% CI, 54.6 to 89.1)
    • Severe cases with onset at least 28 days after administration
      • Efficacy 85.4% (adjusted 95% CI, 54.2 to 96.9)

Efficacy Against South Africa Variant (B.1.351)

  • Vaccine efficacy was maintained against South Africa variant against moderate to severe/critical COVID-19
    • Moderate to severe–critical efficacy
      • Onset at least 14 days after administration: 52.0%
      • Onset at least 28 days after administration: 64.0%
    • Severe-critical efficacy
      • Onset at least 14 days after administration: 73.1%
      • Onset at least 28 days after administration: 81.7%
  • Vaccine safety
    • Reactogenicity was higher with than with placebo but was generally mild to moderate and transient
    • Incidence of serious adverse events did not differ between groups
  • Deaths
    • Vaccine group: 3 deaths (none related to COVID-19)
    • Placebo group: 16 deaths (5 COVID-19 related)


  • The J&J vaccine was effective at preventing  COVID-19 at least 28 days after vaccination, especially against severe/critical COVID-19
  • Efficacy was still high in South Africa, where a majority of COVID-19 cases were due to the South African variant
  • There were no major adverse events associated with vaccination
  • There were no COVID-19 related deaths in the vaccine group

Learn More – Primary Sources:

Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19

ASH Guidelines: Diagnosis and Management of COVID-19 Vaccine-Induced Thrombosis with Thrombocytopenia


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)
    • Thrombocytopenia (current TTS definition <150,000/μL)
    • Positive PF4 ‘HIT’ (heparin-induced thrombocytopenia) ELISA

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



  1. CBC with platelet count and peripheral smear
    • Mean platelet count in published reports: 20,000/μL | There is a range from profound to mild
  2. D-dimers: Most patients have significantly elevated levels
  3. Fibrinogen: Some patients have low levels
  4. 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


  • 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


  • 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

Learn More – Primary Sources:

American Society of Hematology: Thrombosis with Thrombocytopenia Syndrome (also termed Vaccine-induced Thrombotic Thrombocytopenia)

mRNA COVID-19 Vaccine Safety in Pregnant Women


  • 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


  • 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


  • 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)


  • 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

Learn More – Primary Sources:

Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons

Does COVID-19 Vaccination in Breastfeeding Women Produce Detectable Levels of Antibodies in Breast Milk?


  • 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


  • 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


  • 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


  • 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 

Learn More – Primary Sources:

SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women

Potential Pathology Behind AstraZeneca COVID-19 Vaccination and Blood Clots


  • Schultz et al. (NEJM, 2021) describes 5 cases of severe thrombosis and thrombocytopenia following vaccination with the ChAdOx1 (AstraZeneca) COVID-19 vaccine


  • 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


  • 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


  • 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)

Learn More – Primary Sources:

Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination

The Value of Vaccination for Those Previously Infected with SARS-CoV-2


  • 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


  • 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


  • 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


  • 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

Learn More – Primary Sources:

Neutralizing Response against Variants after SARS-CoV-2 Infection and One Dose of BNT162b2

COVID-19 mRNA Vaccine Effectiveness in the Real World Including in Those Partially Immunized


  • 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. (CDC MMWR, 2021) quantified SARS-CoV-2 infections among vaccinated, partially-vaccinated, and non-vaccinated essential personnel every week for 12 weeks


  • 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


  • 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%


  • 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 

Learn More – Primary Sources:

Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers — Eight U.S. Locations, December 2020–March 2021

Vaccines in Pregnant and Lactating Women: Is Immune Response Similar to that of Non-Pregnant Patients?


  • 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


  • 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


  • 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


  • 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

Learn More – Primary Sources:

COVID-19 vaccine response in pregnant and lactating women: a cohort study