• COVID-19 News Team

NEJM Publishes Brief Report on Breakthrough Infections by Variants of Concern

An emerging brief report published in the New England Journal of Medicine sheds light on breakthrough infections by variants of concern. Though breakthrough infections among vaccinated persons are relatively rare and these persons typically experience mild-to-moderate symptoms, the unvaccinated are at higher risk for severe illness. Keep reading to learn more.


SARS-CoV-2 2019 (also referred to as nCoV-19, "novel coronavirus 2019") is an unsegmented single-stranded RNA Betacoronavirus belonging to the family Coronaviridae, which causes the disease COVID-19 (coronavirus disease 2019) in persons with active infection[1].

According to the World Health Organization's report on the origins of the virus, SARS-CoV-2 2019 is probably zoonotic in origin with spillover originating in Wuhan, China[2]. As SARS-CoV-2 2019 genetic replication is driven by RdRp (RNA-dependent RNA polymerase), there is increasing research at the intersection of variants of concerns and molecular machinery which may drive mutational change.[3]

Interestingly, some variants of concern contain substitutions in the ACE2 dependent RBD (receptor binding domain) region of the SARS-CoV-2 spike protein (N.B., the molecular architecture of SARS-CoV-2 2019 is described in detail by Yao et al. in Cell [4]).

Additionally, the Centers for Disease Control and Prevention have published a schema for variant classification, along with documentation concerning the relevant substitutions, available at SARS-CoV-2 Variant Classifications and Definitions (cdc.gov).[5]

Analysis and New Data from NEJM Brief Report

Hacisuleyman et al. (2021) describe breakthrough infections among vaccinated persons in their brief report published in NEJM. Their observations, "indicate a potential risk of illness after successful vaccination and subsequent infection with variant virus." [6]

The findings of Hacisuleyman et al. (2021) support increasingly urgent calls from public health officials for the unvaccinated to get vaccinated. Intentionally unvaccinated persons in the United States are increasingly becoming a threat to efforts to end the pandemic. In fact, they have been referred to as "variant factories," providing the virus the perfect environment to mutate and potentially develop further mutations.[7]

CDC Director, Dr. Rochelle Walensky, recently warned of a "Pandemic of the Unvaccinated." With vaccination rates devastatingly low in much of the South, risk of infection by Delta, the predominant variant of concern, is all but certain for the unvaccinated. According to NY Times, the Delta variant "accounts for more than half of new infections across the country".[8] Moreover, 99% of new COVID-19 deaths are among the unvaccinated.[9]

An Urgent Call to Get Vaccinated

If you or someone you know has not been vaccinated, North Carolina Health Equity Project, Inc. urges you to fight misinformation, get the facts from trusted sources and trusted messengers (cdc.gov, nih.gov, ncdhhs.gov), and talk to your healthcare provider. Current EUA approved vaccines distributed in the United States are safe.

Resources for North Carolinians

COVID-19 vaccines are available to everyone 12 and older. North Carolinians should visit COVID-19 Vaccine Information | NC COVID-19 (ncdhhs.gov) or call 1-888-675-4567 to find a vaccine location. Transportation and home vaccination information is also provided by NC DHHS at https://covid19.ncddhs.gov/vaccines.


[1] Wang et al., The genetic sequence, origin, and diagnosis of SARS-CoV-2 (nih.gov) Eur J Clin Microbiol Infect Dis. 2020 Apr 24 : 1–7.

[2] WHO, Virus origin / Origins of the SARS-CoV-2 virus (who.int)

[3] Naqvi et al., Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach (nih.gov), Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1; 1866(10): 165878

[4] Yao et al., Molecular Architecture of the SARS-CoV-2 Virus, Cell. 2020. 183:1-9

[5] SARS-CoV-2 Variant Classifications and Definitions (cdc.gov)

[6] Hacisuleyman et al., Vaccine Breakthrough Infections with SARS-CoV-2 Variants | NEJM, N Engl J Med 2021; 384:2212-2218

[7] CNN, Unvaccinated people are 'variant factories,' infectious diseases expert says - CNN

[8] NY Times, C.D.C. Director Warns of a ‘Pandemic of the Unvaccinated’ - The New York Times (nytimes.com)

[9] NPR, COVID-19 Deaths Are Rising, And 99% Of Them Are People Who Are Unvaccinated : NPR

Editorial Note

This article has been independently reviewed for accuracy by our Scientific Advisory Board.

Part of health disparities news and research reporting by North Carolina Health Equity Project, Inc. The views expressed by the authors of any cited publication(s) or external link(s) do not necessarily reflect the views of North Carolina Health Equity Project, Inc., nor are any affiliations or endorsements implied.


The Mission and Vision of North Carolina Health Equity Project, Inc.

North Carolina Health Equity Project, Inc., NCHEALTHEQ™, develops adaptive, intelligent, next-generation technologies to improve health outcomes for all people, especially those in marginalized communities. We leverage the power of cross-disciplinary innovation and disruptive technologies including AI/ML, “accelerating research and saving lives.” Learn more at https://www.nchealtheq.org/.

Contact Us

Corporate and Governmental Affairs

North Carolina Health Equity Project, Inc.


+1 336-283-5094

NCHEALTHEQ™ is a trademark of North Carolina Health Equity Project, Incorporated ("NCHEP"). Governance | Terms | Privacy © 2021, NCHEP or its affiliates.

48 views0 comments