Safety Monitoring of COVID-19 mRNA Vaccine First Booster Doses Among Persons Aged ≥12 Years With Presumed Immunocompromise Status

United States, January 12, 2022-March 28, 2022

Anne M. Hause, PhD; James Baggs, PhD; Paige Marquez, MSPH; Winston E. Abara, MD; Jane Gwira Baumblatt, MD; Deborah Thompson, MD; John R. Su, MD; Tanya R. Myers, PhD; Julianne Gee, MPH; Tom T. Shimabukuro, MD; David K. Shay, MD

Disclosures

Morbidity and Mortality Weekly Report. 2022;71(28):899-903. 

In This Article

Abstract and Introduction

Introduction

Persons with moderate to severe immunocompromising conditions are at risk for severe COVID-19, and their immune response to COVID-19 vaccination might not be as robust as the response in persons who are not immunocompromised*.[1] The Advisory Committee on Immunization Practices (ACIP) recommends that immunocompromised persons aged ≥12 years complete a 3-dose primary mRNA COVID-19 vaccination series followed by a first booster dose (dose 4) ≥3 months after dose 3 and a second booster dose (dose 5) ≥4 months after dose 4. To characterize the safety of first booster doses among immunocompromised persons aged ≥12 years during January 12, 2022–March 28, 2022, CDC reviewed adverse events and health impact assessments reported to v-safe and the Vaccine Adverse Event Reporting System (VAERS) during the week after receipt of an mRNA COVID-19 first booster dose. V-safe is a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination. VAERS is a passive surveillance system for all vaccine-associated adverse events co-managed by CDC and the Food and Drug Administration (FDA). A fourth mRNA dose reported to v-safe or VAERS during January 12, 2022–March 28, 2022, was presumed to be an mRNA COVID-19 vaccine booster dose administered to an immunocompromised person because no other population was authorized to receive a fourth dose during that period.[2,3] In the United States, during January 12, 2022–March 28, 2022, approximately 518,113 persons aged ≥12 years received a fourth dose. Among 4,015 v-safe registrants who received a fourth dose, local and systemic reactions were less frequently reported than were those following dose 3 of their primary series. VAERS received 145 reports after fourth doses; 128 (88.3%) were nonserious and 17 (11.7%) were serious. Health care providers, immunocompromised persons, and parents of immunocompromised children should be aware that local and systemic reactions are expected after a first booster mRNA COVID-19 vaccine dose, serious adverse events are rare, and safety findings were consistent with those previously described among nonimmunocompromised persons.[4,5]

V-safe is a voluntary, smartphone–based U.S. active safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination (https://vsafe.cdc.gov/en/). The v-safe platform allows registrants to report receipt of a COVID-19 booster dose; new registrants enter information about all doses received. Coincident with authorization for a booster dose in persons with moderate-to-severe immunocompromising conditions, v-safe was updated to allow registrants to enter information about a fourth dose. Registrants aged ≤15 years are enrolled by a parent or guardian. Health surveys sent daily during the first week after administration of each dose include questions about local injection site and systemic reactions and health impacts.§ CDC's v-safe call center contacts registrants who indicate that medical care was sought after vaccination and encourages completion of a VAERS report, if indicated.

VAERS is a U.S. national passive safety surveillance system that monitors adverse events after vaccination and is managed by CDC and FDA.[6] VAERS accepts reports from health care providers, vaccine manufacturers, and the general public. VAERS reports of hospitalization, prolongation of hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death are classified as serious.** VAERS staff members assign Medical Dictionary for Regulatory Activities (MedDRA) preferred terms to the findings included in VAERS reports.†† Serious reports to VAERS were reviewed by CDC and FDA physicians to form a consensus clinical impression. For reports of death, death certificates and autopsy reports are requested and reviewed by CDC physicians to form an impression about cause of death. Reports of myocarditis and pericarditis, rare adverse events that have been associated with mRNA-based COVID-19 vaccines, were identified by searching for selected MedDRA preferred terms; CDC staff members attempted to collect information about clinical course and determined whether the case definition was met.§§

In v-safe, a fourth mRNA dose administered ≥3 months after dose 3 to a registrant aged ≥12 years during January 12, 2022–March 28, 2022 (data processed April 17, 2022) was presumed to be an mRNA COVID-19 vaccine booster dose administered to an immunocompromised person; this cutoff date was chosen to reduce overlap with fourth doses administered as a second booster to adults aged ≥50 years, which was recommended on March 29, 2022. The odds of reporting an adverse reaction or health impact after a fourth versus a third dose were compared using a multivariable generalized estimated equations model that accounted for demographic variables, vaccine manufacturer, and repeated measures; p-values <0.05 were considered statistically significant. VAERS adverse event reports after a fourth dose among immunocompromised persons were described by seriousness classification (serious versus nonserious), demographic characteristics, and MedDRA preferred terms; a report of a fourth mRNA dose administered to a person aged ≥12 years during January 12, 2022–March 28, 2022 (data processed April 17, 2022) that did not include MedDRA preferred terms for vaccine error was presumed to be an mRNA COVID-19 vaccine booster dose administered to an immunocompromised person. SAS software (version 9.4; SAS Institute) was used to conduct all analyses. These surveillance activities were reviewed by CDC and conducted consistent with applicable federal law and CDC policy.¶¶

*https://doi.org/10.1101/2021.07.08.21259776
https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html
§Health surveys are sent for the most recent dose entered via text messages that link to web-based surveys on days 0–7 after receipt of a vaccine dose; then weekly through 6 weeks after vaccination; and then at 3, 6, and 12 months after vaccination. Local injection site reactions include itching, pain, redness, and swelling. Systemic reactions include abdominal pain, myalgia, chills, diarrhea, fatigue, fever, headache, joint pain, nausea, rash, and vomiting. Health impacts include inability to perform normal daily activities, inability to work or attend school, and receipt of medical care.
Health care providers are encouraged by CDC and FDA to report adverse events to VAERS and are required by COVID-19 vaccine Emergency Use Authorizations to report certain adverse events after vaccination to VAERS, including death. https://vaers.hhs.gov/faq.html
**VAERS reports are classified as serious based on the Code of Federal Regulations Title 21. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr
††Each VAERS report might be assigned at least one MedDRA preferred term. A MedDRA-coded event does not indicate a medically confirmed diagnosis. https://www.meddra.org/how-to-use/basics/hierarchy
§§In VAERS, acute myocarditis was defined as presence of new onset or worsening of one or more of the following signs or symptoms: chest pain, pressure, discomfort, dyspnea, shortness of breath, pain with breathing, palpitations, or syncope; or two or more of the following signs or symptoms in children aged ≤11 years: irritability, vomiting, poor feeding, tachypnea, or lethargy; and one or more new finding of elevated troponin, electrocardiogram findings consistent with myocarditis, abnormal cardiac function or wall motion on echocardiogram, cardiac magnetic resonance imaging findings consistent with myocarditis, or histopathologic findings consistent with myocarditis; and no other identifiable cause for these findings.
¶¶45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.

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