Current Research on Breakthrough Infections by COVID-19 Variants

July 19, 2021

Although tremendous progress has been made in the fight against SARS-CoV-2 with the authorization of vaccines, emerging variants of SARS-CoV-2 are of clinical concern [1]. The rise of viral variants, particularly in the S gene, threaten the continued efficacy of the current vaccines [1]. These concerns have pushed researchers to understand the ability of variants to evade vaccine-induced immunity and cause breakthrough COVID-19 infections or illness [1].

Efforts to track viral variants are ongoing [2]. Many research groups are sequencing viral isolates and sharing their data on public databases, such as the Global Initiative on Sharing All Influenza Data (GISAID), allowing for collaboration between scientists to track the ways in which SARS-CoV-2 is evolving [2]. At present, there are four variants of concern with increased transmissibility that have contributed to the reversal of the decreases in SARS-CoV-2 infection rates that occurred in many countries earlier this year: B.1.1.7 (alpha), P.1 (gamma), B.1.351 (beta), and B.1.617.2 (delta) [2]. According to recent data released by the Centers for Disease Control and Prevention (CDC), the highly contagious delta variant now accounts for more than 51% of SARS-CoV-2 infection in the United States [3].

Breakthrough cases are SAR-CoV-2 infections that bypass vaccine-induced immunity [6]. They are rare and most times asymptomatic [6]. The CDC stopped counting all breakthrough cases after May 1, 2021 and currently only tracks those that result in hospitalization or death [6]. As of April 30, 2021, a total of 10,262 COVID-19 vaccine breakthrough infections had been reported from 46 U.S. states and territories [4]. At that time, roughly 101 million people in the country had been fully vaccinated against SARS-CoV-2 [5]. Among these breakthrough cases, 63% occurred in females, and the median patient age was 58 years old [4]. Only 10% of cases resulted in hospitalization, and 2% of cases resulted in death [4]. The median age of patients who died was 82 years old [4].

Dr. Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia, emphasizes the need for people to continue to get vaccinated despite the breakthrough cases [7]. Although some of the variants, particularly beta, may be more likely to evade vaccine-induced protection, the current vaccines have demonstrated good protection against the variants overall [7]. The Massachusetts Department of Public Health revealed that, as of June 12, there were 3,791 breakthrough infections among more than 3.7 million fully vaccinated people [5]. With an even lower breakthrough case rate, the California Department of Health reported that, as of June 2, there were 5,723 breakthrough cases among more than 17.5 million fully vaccinated people [7].

According to Dr. William Schaffner, medical director of the National Foundation of Infectious Diseases, breakthrough infections are likely to decrease as more people get vaccinated and community transmission rates fall [7]. Efforts to advance a new vaccine booster may also aid in protection against emerging SARS-CoV-2 variants [1].


  1. Hacisuleyman, E., Hale, C., Saito, Y. etc. (2021). Vaccine breakthrough infections with SARS-CoV-2 variants. New England Journal of Medicine384(23), 2212-2218. doi:10.1056/NEJMoa2105000
  2. Krause, P., Fleming, T., Longini, I. etc. (2021). SARS-CoV-2 Variants and Vaccines. New England Journal of Medicine. doi:10.1056/NEJMsr2105280
  3. Greenhalgh, J., & Stein, R. (2021). Delta Is Now the Dominant Coronavirus Variant in The U.S. Retrieved 7 July 2021, from
  4. CDC COVID-19 Vaccine Breakthrough Case Investigations Team (2021). COVID-19 Vaccine Breakthrough Infections Reported to CDC – United States, January 1-April 30, 2021. MMWR. Morbidity and mortality weekly report70(21), 792–793. doi:10.15585/mmwr.mm7021e3
  5. Markos, M. (2021). Nearly 4,000 Breakthrough COVID Infections Have Now Been Reported in Mass. Retrieved from
  6. Mendez, R. (2021). CDC says roughly 4,100 people have been hospitalized or died with Covid breakthrough infections after vaccination. Retrieved from
  7. Anthes, E. (2021). Reports of Severe Covid or Death After Vaccination Are Rare, but Not Unexpected. Retrieved from