An Update on COVID-19 Vaccine Related Anaphylaxis: Cases Remain Rare
BACKGROUND AND PURPOSE:
Initial reporting rates of anaphylaxis in the US
Moderna: 2.5 cases per million doses (December 14 to 23, 2020)
Pfizer-BioNTech: 11.1 cases per million doses (December 21 to January 10, 2021)
Shimabukuro et al. (JAMA, 2021) provide an update regarding anaphylaxis rates following vaccination
METHODS:
Data sources
Vaccine Adverse Event Reporting System (VAERS)
RESULTS:
Doses administered in US between December 14, 2020 and January 18, 2021
Moderna: 7,581,429 doses
Pfizer-BioNTech: 9,943,247 doses
There were 66 total anaphylaxis cases after vaccine administration
Moderna: 19 total cases
Reporting rate 2.5 cases per million doses
Pfizer-BioNTech: 47 total cases
Reporting rate 4.7 cases per million doses
Anaphylaxis case characteristics
Median (range) minutes to symptom onset
Moderna: 10 minutes (1 to 45 minutes)
Pfizer-BioNTech: 10 minutes (<1 minute to 19 hours)
Occurred in persons with a history of allergic reactions
Moderna: 84%
Pfizer-BioNTech: 77%
Occurred in persons with a history of anaphylaxis
Moderna: 26%
Pfizer-BioNTech: 34%
No deaths have been reported due to vaccine-related anaphylaxis
CONCLUSION:
Millions of doses of the Moderna and Pfizer-BioNTech COVID-19 vaccines have been administered in the US
Anaphylaxis is a rare event
The reporting rate is 2.5 (Moderna) and 4.7 (Pfizer-BioNTech) cases per million doses
Immediate epinephrine administration is indicated for all cases of anaphylaxis
The authors conclude
When considered in the context of morbidity and mortality from COVID-19, the benefits of vaccination far outweigh the risk of anaphylaxis, which is treatable
Efficacy of the Novavax SARS-CoV-2 Vaccine Against UK and South African Variants
BACKGROUND AND PURPOSE:
Novavax’s SARS-CoV-2 vaccine is 95.6% effective against the original SARS-CoV-2 variant, requires 2 doses 3 weeks apart, and can be stored at 2 to 8 degrees Celsius
The BMJ (Feb 2021) summarizes interim results on the vaccine’s effectiveness against the UK and South African variants of SARS-CoV-2
METHODS:
Interim results from a phase III trial in the UK and a phase II trial in South Africa
Participants
Individuals aged 18 to 84
Interventions
Two doses of the Novavax vaccine administered 3 weeks apart
Placebo
RESULTS:
Participants
UK: 5,000
South Africa: 4400
UK phase III trial
SARS-CoV-2 infections identified
Placebo group: 56 cases
Vaccine group: 6 cases
Only one severe COVID-19 case was identified, and this was in the placebo group
Of all cases identified, 32 were of the UK variant
South African phase II trial
SARS-CoV-2 infections identified
Placebo group: 29 cases
Vaccine group: 15 cases
Only one severe COVID-19 case was identified, and this was in the placebo group
In preliminary sequencing data of 27 cases, 93% involved the South African variant
CONCLUSION:
Preliminary interim data indicates that the Novavax SARS-CoV2 vaccine is 85.6% effective against the UK variant (B.1.1.7) and 60% effective against the South African variant (B.1.351)
Clinical Trials are ongoing, including in the US and Mexico
An Assessment of Anaphylaxis Risk Following Moderna COVID-19 Vaccination
BACKGROUND AND PURPOSE:
As of January 10, 2021, approximately 4-million first doses of the Moderna COVID-19 vaccine have been administered in the U.S.
Rare cases of anaphylaxis and other allergic reactions have been reported with the Pfizer-BioNTech COVID-19 vaccine, another mRNA-based vaccine
The CDC COVID-19 response team (MMWR, 2021) reported on cases of allergic reactions, including anaphylaxis, associated with first-dose vaccination of the Moderna vaccine
METHODS:
Data sources
Vaccine Adverse Event Reporting System (VAERS)
RESULTS:
1266 adverse events
108 case reports identified for further review for possible cases of allergic reaction, including anaphylaxis
Anaphylaxis
Anaphylaxis cases: 10 (all women)
Anaphylaxis rate: 2.5 cases per million doses
Median age: 47 years (range 31 to 63 years)
Cases with history of allergies or allergic reactions: 9
5 had a history of anaphylaxis
Median interval from vaccine receipt to symptom onset: 7.5 minutes (range 1 to 45 minutes) | 9 cases within 15 minutes
All patients received IM epinephrine and 6 hospitalized
5 ICU | 4 intubated
Follow-up (available in 8 cases)
All recovered or discharged home
Other allergic reactions and adverse events
Other non-anaphylaxis allergic reactions
43 cases within 0 to 1 day risk window
60% (26/43) classified as nonserious
Commonly reported symptoms: Pruritus | Rash | Itchy sensations in the mouth and throat | Sensations of throat closure | Respiratory symptoms
CONCLUSION:
Anaphylaxis following the first dose of the Moderna vaccine is very rare, and occurred within 45 minutes of receipt with a median time of 7.5 minutes
The CDC recommends that
Persons with an immediate allergic reaction to the first dose of an mRNA COVID-19 vaccine should not receive additional doses of either of the mRNA COVID-19 vaccines
In addition to screening for contraindications and precautions before administering COVID-19 vaccines, vaccine locations should have the necessary supplies and trained staff members available to manage anaphylaxis, implement postvaccination observation periods, immediately treat persons experiencing anaphylaxis signs and symptoms with intramuscular injection of epinephrine, and transport patients to facilities where they can receive advanced medical care
Safety and Efficacy of AstraZeneca Oxford’s COVID-19 Vaccine
BACKGROUND AND PURPOSE:
AstraZeneca Oxford’s ChAdOx1 nCoV-19 vaccine uses an adenoviral vector ChAdOx1 that contains the SARS-CoV-2 structural surface glycoprotein antigen
Voysey et al. (Lancet, 2020) evaluated the safety and efficacy of the AstraZeneca Oxford’s ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials
METHODS:
Pooled data from four ongoing blinded, randomized, controlled trials (COV001-3 are single blind | COV005 is double blind)
Low dose/Standard dose (LD/SD) cohort: Subset in the UK trial received a half dose as their first dose and a standard dose as their second dose
Control
Meningococcal group A, C, W, and Y conjugate vaccine OR saline
Note: The lower dose (LD) was noted during quality control procedures (for COV002 trial) and the protocol was amended following review and approval
Study design
Analysis was according to treatment received, with a data cutoff on Nov 4, 2020
Vaccine efficacy was calculated as 1-relative risk derived from a robust Poisson regression model adjusted for age
Primary outcomes
Primary efficacy analysis: symptomatic COVID-19 in seronegative participants with a positive PCR test >14 days after a second dose of vaccine
RESULTS:
23,848 participants enrolled | 11,636 were included in the interim primary efficacy analysis
Efficacy
SD/SD vaccine efficacy: 62.1% (95% CI, 41.0 to 75.7%)
ChAdOx1 nCoV-19 group: 0.6% developed COVID-19
Control: 1.6% developed COVID-19
LD/SD vaccine efficacy: 90.0% (95% CI, 67.4 to 97.0%)
ChAdOx1 nCoV-19 group: 0.2% developed COVID-19
Control group: 2.2% developed COVID-19
Overall vaccine efficacy across both groups was: 70.4% (95% CI, 54.8 to 80.6%)
ChAdOx1 nCoV-19 group: 0.5% developed COVID-19
Control group: 1.7% developed COVID-19
Safety
From 21 days after the first dose, there were 10 people hospitalized for COVID-19, all of which were in the control arm
Severe COVID-19: 2 participants
Deaths: 1 participant
During 74,341 person-months of safety follow-up (median follow-up 3.4 months, IQR 1.3 to 4.8 months) there were 175 severe adverse events among 168 participants
ChAdOx1 nCoV-19 group: 84 events
Control group: 91 events
3 adverse events were classified as possibly related to the vaccine
ChAdOx1 nCoV-19 group: 1 participant
Control group: 1 participant
Still masked: 1 participant
CONCLUSION:
The AstraZeneca Oxford SARS-CoV-2 vaccine, the first peer-review study of a viral-vectored coronavirus, is safe and efficacious for the prevention of symptomatic COVID-19
Overall efficacy was 70.4%
Results were generalizable across diverse settings
Additional benefit of a viral-vectored vaccine is the use of routine refrigerated cold chain vs ultra-low temperature freezers required for mRNA vaccines
The authors address the increased efficacy of LD/SD dosing vs SD/SD and state
Efficacy of 90.0% seen in those who received a low dose as prime in the UK was intriguingly high compared with the other findings in the study
Although there is a possibility that chance might play a part in such divergent results, a similar contrast in efficacy between the LD/SD and SD/SD recipients with asymptomatic infections provides support for the observation
The Moderna Vaccine: Study Results Presented to ACIP CDC Committee
PURPOSE:
The FDA has issued an Emergency Use Authorization (EUA) for the Moderna COVID-19 (mRNA-1273)
For ages ≥18 years to prevent COVID-19
Lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2
2 doses (100 μg, 0.5 mL each) administered IM 28 days apart
The body of evidence for the Moderna COVID-19 vaccine was primarily informed by one large trial
Oliver et al. (MMWR, 2020) on behalf of ACIP, assessed the data and report on the findings and ACIP interim recommendations
METHODS:
Randomized, double-blind, placebo-controlled Phase III clinical trial
Participants
≥18 years
Pregnant and lactating women were not included in this dataset
Randomized 1:1 to 2 groups
Vaccine
Saline placebo
Primary study outcome
Efficacy: Prevention of symptomatic, laboratory-confirmed COVID-19 among persons without evidence of previous SARS-CoV-2 infection
RESULTS:
30,351 enrolled participants
Vaccine: 15,185
Placebo: 15,166
Age: 18 to 95 (median: 52 years)
Vaccine Efficacy
The vaccine demonstrated high efficacy after 2 doses (7 week follow-up)
Vaccine: 11 cases
Placebo: 185 cases
Vaccine efficacy: 94.1% (95% CI, 89.3% to 96.8%)
In this final scheduled analysis (9 week follow-up) similar results were obtained
Vaccine efficacy: 94.5% (95% CI, 86.5 to 97.8)
High efficacy was observed across age, sex, race, and ethnicity categories and among persons with underlying medical conditions
Adverse Events
Systemic adverse reactions were more commonly reported after the second dose
More frequent and severe in persons aged 18 to 64 years than in those aged ≥65 years
Most local and systemic adverse reactions occurred within the first 1 to 2 days after vaccine receipt and resolved in a median of 2 to 3 days
Severe local or systemic adverse reactions (grade ≥3 reactions)
Occurred more commonly in vaccine recipients (21.6%) vs placebo recipients (4.4%)
Among vaccine recipients, 9.1% reported a grade ≥3 local injection site reaction, and 16.5% reported a grade ≥3 systemic adverse reaction
Serious adverse events: Death | Life-threatening | Requires inpatient hospitalization or prolongation of existing hospitalization | Results in persistent disability/incapacity
No difference between groups (1% in both)
No specific safety concerns were identified in subgroup analyses by age, race, ethnicity, underlying medical conditions, or previous SARS-CoV-2 infection
Detailed summary of safety data and adverse events can be found in ‘Learn More-Primary Sources’ below
CONCLUSION:
Based on the above data, ACIP issued an interim recommendation for the use of the Moderna vaccine
ACIP concluded that
COVID-19 is a major public health problem and that use of the Moderna COVID-19 vaccine is a reasonable and efficient allocation of resources. Whereas there might be uncertainty about how all populations value the vaccine, it was determined that for most populations, the desirable effects outweigh the undesirable effects, making the vaccine acceptable to implementation stakeholders
Safety and Efficacy Data of BNT162b2 COVID-19 Vaccine
BACKGROUND AND PURPOSE:
BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein
The messenger RNA (mRNA) used in this vaccine includes the code used by SARS-CoV-2 to produce spike protein that helps the virus enter and infect cells
Following vaccination, the mRNA enters the vaccine recipient’s normal cells that will use the mRNA code to produce spike proteins that will generate an immune reaction
In the future, if the vaccine recipient is exposed to the SARS-CoV-2 virus, the antibodies generated by this immune system reaction will recognize and neutralize the invading virus
Polack et al. (NEJM, 2020) report on the safety and efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine in preventing COVID-19
Efficacy of the vaccine against laboratory-confirmed COVID-19
Safety
RESULTS:
42,448 participants were randomized and received injections
BNT162b2: 21,720 participants
Placebo: 21,728 participants
BNT162b2 was 95% effective in preventing COVID-19
Placebo: 162 cases
BNT12b2: 8 cases (onset at least 7 days after the second dose)
(95% CI, 90.3 to 97.6)
Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by
Age | Sex | Race | BMI | Coexisting conditions
There were 10 cases of severe COVID-19 with onset after the first dose
Placebo: 9 cases
BNT162b2: 1 case
Side effects
Mild-to-moderate pain at the injection site
Fatigue
Headache
Fever (≥38°C): After second dose: 16% of younger vaccine recipients (16 to 55 years) | 11% of older recipients (>55 years)
Fever ≥38.9 to 40°C
After first dose: 0.2% of vaccine recipients | 0.1% of placebo
After second dose: 0.8% of vaccine recipients | 0.1% placebo
Fever >40.0°C
2 participants each in the vaccine and placebo groups
Incidence of serious adverse events was low and similar for the vaccine and placebo groups
CONCLUSION:
Two doses of BNT162b2 spaced 21 days apart conferred 95% protection against COVID-19 in people aged 16 and over with a safety profile similar to other vaccines
This study does not address the following populations
Adolescents | Children | Pregnant women
Vaccine requires very cold temperatures for shipping and long-term storage
Standard refrigerators can be used for up to 5 days when ready for use
The authors state
The data presented in this report have significance beyond the performance of this vaccine candidate
The results demonstrate that Covid-19 can be prevented by immunization, provide proof of concept that RNA-based vaccines are a promising new approach for protecting humans against infectious diseases, and demonstrate the speed with which an RNA-based vaccine can be developed with a sufficient investment of resources
Vaccination in Pregnancy: CDC Recommendations and ACOG Update
CLINICAL ACTIONS:
ACOG has released a Committee Opinion on Maternal Immunization. During pregnancy, all women should be evaluated for vaccination requirements. Acceptance of vaccination during pregnancy is much higher when the recommendation comes from a woman’s obstetrician or obstetrical provider. The Committee Opinion states
There is no evidence of adverse fetal effects from vaccinating pregnant women with inactivated virus, bacterial vaccines, or toxoids, and a growing body of data demonstrate the safety of such use.
Recommended for all women
Tdap (Tetanus, Diphtheria and Pertussis)
Vaccinate as early in the 27 to 36 week gestation window as possible to maximize maternal antibody response and passive antibody transfer to the infant (see ‘Related ObG Topics’ below for evidence of newborn protection through first year of life)
If not vaccinated previously before or during pregnancy, administer vaccine immediately postpartum
Wound management: administer Tdap if indicated
If unknown tetanus vaccine status: administer 3 vaccinations containing tetanus and reduced diphtheria toxoids at 0, 4 weeks and 6 to 12 months; Tdap should replace one dose of Td, preferably given between 27 – 36 weeks gestation
Health-care personnel should administer a dose of Tdap during each pregnancy irrespective of the patient’s prior history of receiving Tdap
Influenza (inactivated or recombinant)
Routine influenza vaccination (inactivated influenza vaccine or recombinant influenza vaccine) is recommended for all women who are or will become pregnant (in any trimester) during influenza season
In the United States, usually early October through late March
Hepatitis B (HepB)
Pregnancy is not a contraindication to vaccination
Available vaccines contain noninfectious HBsAg and should cause no risk of infection to the fetus
If pregnant and not already vaccinated: Vaccinate with HepB since all adults 19 through 59 years of age are recommended to receive HepB vaccination
Respiratory Syncytial Virus (RSV)
Single dose between 32w0d and 36w6d
For prevention of RSV lower respiratory tract infection in infants
Use seasonal administration (September through January)
May be administered with other vaccines routinely advised for use during pregnancy
Immediate protection for infant if maternal vaccination at least 14 days before birth
Note: A monoclonal antibody (nirsevimab) is available for infants if maternal RSV vaccination has not occurred or vaccine was given but delivery was prior to 34 weeks | Nirsevimab is considered safe and effective for the prevention of RSV in infants | ACOG recommends that patients should be counseled regarding monoclonal antibodies as an alternative at birth including whether the antibodies will be available
Key Counseling points
Maternal RSV Vaccine Benefits: Newborn has immediate protection at birth | Fewer vaccines required at birth
Monoclonal Antibody Benefits: Protection may last longer | Direct placental delivery vs passive transfer
Consider vaccination if indicated or under some circumstances
Hepatitis A (HepA)
Should be given if
Travel to or work in countries with high or intermediate hepatitis A endemicity
Users of illegal drugs
Anticipate having close personal contact with an international adoptee from a country of higher or intermediate endemic during the first 60 days following the adoptee’s arrival to the U.S.
If receiving clotting factor concentrates
People who work with hepatitis A virus (HAV) in research lab settings
Chronic liver disease
Post-exposure to HAV (recent, within 2 weeks): If 40 years of age or younger
If over age 40, immune globulin is preferred
Meningococcal (MenACWY or MPSV4)
Should be given if
Anatomic or functional asplenic or persistent complement deficiency
Travel to countries in which meningococcal disease is hyper-endemic or epidemic (e.g., the “meningitis belt” of Sub-Saharan Africa)
Microbiologists routinely exposed to isolates of N. mengitidis
First-year college students through age 21 who live in residence halls and not previously vaccinated or received their first dose prior to age 16 years
Military recruits
HIV infection
Polio: Inactivated Polio Vaccine (IPV)
Can be used if needed if at risk for infection and immediate protection is required
Pneumococcal vaccination
ACOG recommends the following pneumococcal vaccines may be given to pregnant individuals at high risk of severe illness from pneumococcal disease
Pneumococcal conjugate vaccines: PCV15 and PCV20
Pneumococcal polysaccharide vaccine: PPSV23
CDC recommends that individuals aged 19 to 64 years with certain underlying medical conditions or other risk factors who have not previously received PCV or whose previous vaccination history is unknown should receive 1 dose of PCV (either PCV20 or PCV15) and if PCV15 is used, it should be followed by a dose of PPSV23
The following vaccines are not recommended in pregnancy
Human Papillomavirus (HPV)
If series started prior to pregnancy, delay remainder of 3-dose series until after completion of pregnancy
No intervention is necessary if dose administered during pregnancy
The following vaccines are contraindicated in pregnancy
Live attenuated Influenza vaccine (LAIV), also known as the “nasal spray” flu vaccine
Mumps-Measles-Rubella (MMR)
Varicella
Zoster
Live-attenuated VZV-based vaccine
Recombinant Zoster (Shingles) Vaccine
SYNOPSIS:
There is no evidence that there is risk to a fetus with inactivated virus or bacterial vaccines or toxoids. Live vaccines are contraindicated during pregnancy due to a theoretical risk. The CDC and ACOG website links below provide additional information to dosing and further contraindications and precautions.
COVID-19
ACOG addresses the topic of COVID-19 vaccination in pregnancy and recommends that
ACOG strongly recommends that all eligible persons receive a COVID-19 vaccine or vaccine series. Obstetrician-gynecologists and other women’s health care practitioners should lead by example by being vaccinated and encouraging eligible patients to be vaccinated as well
ACOG recommends that pregnant individuals be vaccinated against COVID-19
ACOG recommends that lactating individuals be vaccinated against COVID-19
While a conversation with a clinician may be helpful, it is not a requirement prior to vaccination, as this may cause unnecessary barriers to access
Note: For additional information on this topic, see ‘Learn More – Primary Sources’ and ‘Related ObG Topics’, below
KEY POINTS:
ACOG has updated recommendations to include hepatitis B vaccination for all unvaccinated pregnant adults and pneumococcal vaccination for pregnant individuals at increased risk of severe pneumococcal disease
Contraindications to vaccination include a history of a serious reaction or anaphylaxis to a previous vaccine or component of a vaccine
Report adverse reactions or concerns to vaccination to the Vaccine Adverse Event Reporting System (VAERS) – link in ‘learn more’ below
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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.
The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Disclaimer
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
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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