Morbidity and Mortality Weekly Report

Early Release / Vol. 70 May 25, 2021

COVID-19 Vaccine Breakthrough Infections Reported to CDC — United States,

January 1–April 30, 2021
CDC COVID-19 Vaccine Breakthrough Case Investigations Team

COVID-19 vaccines are a critical tool for controlling the 995 (10%) patients were known to be hospitalized, and
ongoing global pandemic. The Food and Drug Administration 160 (2%) patients died. Among the 995 hospitalized patients,
(FDA) has issued Emergency Use Authorizations for three 289 (29%) were asymptomatic or hospitalized for a reason
COVID-19 vaccines for use in the United States.* In large, unrelated to COVID-19. The median age of patients who died
randomized-controlled trials, each vaccine was found to be was 82 years (interquartile range = 71–89 years); 28 (18%)
safe and efficacious in preventing symptomatic, laboratory- decedents were asymptomatic or died from a cause unrelated
confirmed COVID-19 (1–3). Despite the high level of vaccine to COVID-19. Sequence data were available from 555 (5%)
efficacy, a small percentage of fully vaccinated persons (i.e. reported cases, 356 (64%) of which were identified as
received all recommended doses of an FDA-authorized SARS-CoV-2 variants of concern, § including B.1.1.7
COVID-19 vaccine) will develop symptomatic or asymptom- (199; 56%), B.1.429 (88; 25%), B.1.427 (28; 8%), P.1
atic infections with SARS-CoV-2, the virus that causes (28; 8%), and B.1.351 (13; 4%).
COVID-19 (2–8). As of April 30, 2021, approximately 101 million persons in
CDC is working with state and territorial health departments the United States had been fully vaccinated against COVID-19.¶
to investigate SARS-CoV-2 infections among persons who However, during the surveillance period, SARS-CoV-2 trans-
are fully vaccinated and to monitor trends in case character- mission continued at high levels in many parts of the country,
istics and SARS-CoV-2 variants identified from persons with with approximately 355,000 COVID-19 cases reported nation-
these infections. For this surveillance, a vaccine breakthrough ally during the week of April 24–30, 2021.** Even though
infection is defined as the detection of SARS-CoV-2 RNA FDA-authorized vaccines are highly effective, breakthrough
or antigen in a respiratory specimen collected from a person cases are expected, especially before population immunity
≥14 days after receipt of all recommended doses of an FDA- reaches sufficient levels to further decrease transmission.
authorized COVID-19 vaccine. State health departments However, vaccine breakthrough infections occur in only a small
voluntarily report vaccine breakthrough infections to CDC.† fraction of all vaccinated persons and account for a small
When possible, genomic sequencing is performed on respira- percentage of all COVID-19 cases (5–8). The number of
tory specimens that test positive for SARS-CoV-2 RNA (9). COVID-19 cases, hospitalizations, and deaths that will be
A total of 10,262 SARS-CoV-2 vaccine breakthrough infec- prevented among vaccinated persons will far exceed the number
tions had been reported from 46 U.S. states and territories as of vaccine breakthrough cases. To date, the age and sex distri-
of April 30, 2021. Among these cases, 6,446 (63%) occurred bution of reported vaccine breakthrough infections reflects the
in females, and the median patient age was 58 years (inter- fully vaccinated U.S. population.†† The proportion of reported
quartile range = 40–74 years). Based on preliminary data, 2,725
§ https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-
(27%) vaccine breakthrough infections were asymptomatic, surveillance/variant-info.html
¶ https://covid.cdc.gov/covid-data-tracker/#vaccinations
* https://www.fda.gov/emergency-preparedness-and-response/coronavirus-
disease-2019-covid-19/covid-19-vaccines ** https://covid.cdc.gov/covid-data-tracker/#cases_totalcases
† https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough- †† https://covid.cdc.gov/covid-data-tracker/#vaccination-demographic
cases.html

U.S. Department of Health and Human Services

Centers for Disease Control and Prevention
 Early Release

vaccine breakthrough infections attributed to variants of concern Corresponding author: Marc Fischer, [email protected].
has also been similar to the proportion of these variants circulat- All authors have completed and submitted the International
ing throughout the United States. During March 28–April 10, Committee of Medical Journal Editors form for disclosure of potential
2021, the aforementioned variants of concern accounted for conflicts of interest. No potential conflicts of interest were disclosed.
70% of the weighted estimates of SARS-CoV-2 lineages submit-
References
ted to CDC’s national genomic surveillance.§§
The findings in this report are subject to at least two 1. Polack FP, Thomas SJ, Kitchin N, et al.; C4591001 Clinical Trial
Group. Safety and efficacy of the BNT162b2 mRNA COVID-19
limitations. First, the number of reported COVID-19 vaccine vaccine. N Engl J Med 2020;383:2603–15. PMID:33301246 https://
breakthrough cases is likely a substantial undercount of all doi.org/10.1056/NEJMoa2034577
SARS-CoV-2 infections among fully vaccinated persons. The 2. Baden LR, El Sahly HM, Essink B, et al.; COVE Study Group.
Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl
national surveillance system relies on passive and voluntary J Med 2021;384:403–16. PMID:33378609 https://doi.org/10.1056/
reporting, and data might not be complete or representative. NEJMoa2035389
Many persons with vaccine breakthrough infections, especially 3. Sadoff J, Gray G, Vandebosch A, et al.; ENSEMBLE Study Group.
Safety and efficacy of single-dose Ad26.COV2.S vaccine against
those who are asymptomatic or who experience mild illness, COVID-19. N Engl J Med 2021;NEJMoa2101544. Epub April 21,
might not seek testing. Second, SARS-CoV-2 sequence data 2021. PMID:33882225 https://doi.org/10.1056/NEJMoa2101544
are available for only a small proportion of the reported cases. 4. Thompson MG, Burgess JL, Naleway AL, et al. Interim estimates of
Beginning May 1, 2021, CDC transitioned from monitoring vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19
vaccines in preventing SARS-CoV-2 infection among health care
all reported COVID-19 vaccine breakthrough infections to personnel, first responders, and other essential and frontline workers—
investigating only those among patients who are hospitalized eight U.S. locations, December 2020–March 2021. MMWR Morb
or die, thereby focusing on the cases of highest clinical and Mortal Wkly Rep 2021;70:495–500. PMID:33793460 https://doi.
org/10.15585/mmwr.mm7013e3
public health significance. CDC will continue to lead studies 5. Tenforde MW, Olson SM, Self WH, et al.; IVY Network; HAIVEN
in multiple U.S. sites to evaluate vaccine effectiveness and Investigators. Effectiveness of Pfizer-BioNTech and Moderna vaccines against
collect information on all COVID-19 vaccine breakthrough COVID-19 among hospitalized adults aged ≥65 years—United States,
January–March 2021. MMWR Morb Mortal Wkly Rep 2021;70:674–9.
infections regardless of clinical status. Additional information PMID:33956782 https://doi.org/10.15585/mmwr.mm7018e1
and resources to help public health departments and laborato- 6. Tande AJ, Pollock BD, Shah ND, et al. Impact of the COVID-19 vaccine
ries investigate and report COVID-19 vaccine breakthrough on asymptomatic infection among patients undergoing pre-procedural
cases are available at https://www.cdc.gov/vaccines/covid-19/ COVID-19 molecular screening. Clin Infect Dis 2021;ciab229. Epub
March 10, 2021. PMID:33704435 https://doi.org/10.1093/cid/ciab229
health-departments/breakthrough-cases.html. 7. Swift MD, Breeher LE, Tande AJ, et al. Effectiveness of mRNA
FDA-authorized COVID-19 vaccines are safe and effective COVID-19 vaccines against SARS-CoV-2 infection in a cohort of
(1–8). CDC recommends that all persons aged ≥12 years be healthcare personnel. Clin Infect Dis 2021;ciab361. Epub April 26,
2021. PMID:33900384 https://doi.org/10.1093/cid/ciab361
vaccinated with an FDA-authorized COVID-19 vaccine¶¶ (10). 8. Haas EJ, Angulo FJ, McLaughlin JM, et al. Impact and effectiveness
of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and
§§ https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-
COVID-19 cases, hospitalisations, and deaths following a nationwide
proportions.html
vaccination campaign in Israel: an observational study using national
¶¶ https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html
surveillance data. Lancet 2021;397:1819–29. PMID:33964222 https://
Acknowledgments doi.org/10.1016/S0140-6736(21)00947-8
9. Paden CR, Tao Y, Queen K, et al. Rapid, sensitive, full-genome
Suxiang Tong; CDC COVID-19 Strain Surveillance and Emerging sequencing of severe acute respiratory syndrome coronavirus 2. Emerg
Variant Team, Laboratory and Testing Task Force. Infect Dis 2020;26:2401–5. PMID:32610037 https://doi.org/10.3201/
eid2610.201800
CDC COVID-19 Vaccine Breakthrough Case 10. Wallace M, Woodworth KR, Gargano JW, et al. The Advisory
Investigations Team Committee on Immunization Practices’ interim recommendation
for use of Pfizer-BioNTech COVID-19 vaccine in adolescents aged
Meseret Birhane, CDC; Sara Bressler, CDC; Gregory Chang, 12–15 years—United States, May 2021. MMWR Morb Mortal Wkly
CDC; Thomas Clark, CDC; Layne Dorough, CDC; Marc Fischer, Rep 2021;70:749–52. https://www.cdc.gov/mmwr/volumes/70/wr/
CDC; Louise Francois Watkins, CDC; Jason M. Goldstein, CDC; mm7020e1.htm?s_cid=mm7020e1_w
Kiersten Kugeler, CDC; Gayle Langley, CDC; Kristin Lecy, CDC;
Stacey Martin, CDC; Felicita Medalla, CDC; Kiren Mitruka, CDC;
Leisha Nolen, CDC; Katrin Sadigh, CDC; Robin Spratling, CDC;
Gail Thompson, CDC; Alma Trujillo, CDC.

2 MMWR  /  May 25, 2021  /  Vol. 70

 Early Release

Readers who have difficulty accessing this PDF file may access the HTML file at https://www.cdc.gov/mmwr/volumes/70/wr/mm7021e3.
htm?s_cid=mm7021e3_w. Address all inquiries about the MMWR Series, including material to be considered for publication, to Editor,
MMWR Series, Mailstop V25-5, CDC, 1600 Clifton Rd., N.E., Atlanta, GA 30329-4027 or to [email protected].

MMWR  /  May 25, 2021  /  Vol. 70 3