How COVID vaccines protected Americans against the Delta variant

Current vaccines against the coronavirus disease 2019 (COVID-19) are considered to be highly effective in preventing severe illness caused by infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Study: Covid-19 Rates by Time since Vaccination during Delta Variant Predominance. Image Credit: Mirza Kadic /


However, breakthrough infections still occur due to reduced vaccine effectiveness (VE) against new SARS-CoV-2 variants and waning immunity. In fact, data from six months follow-up of clinical trials reported a 6% reduction in VE every two months for the Pfizer-BioNTech BNT162b2 vaccine, while no such reduction was observed in the case of the Moderna mRNA-1273 vaccine.

The United States Food and Drug Administration (FDA) recently authorized vaccine boosters, which accounts for a total of three vaccine doses, for adults who are 18 years of age or older at least six months after they had received their initial messenger ribonucleic acid (mRNA) vaccination. Individuals who received the Johnson & Johnson adenovirus vector Ad26.COV2.S vaccine, which was originally a single-dose vaccine, was also advised to get a booster two months post-vaccination. However, data on the extent of waning immunity against SARS-CoV-2 infection and death are limited especially for mRNA-1273 and Ad26.COV2.S vaccines.

A new study published in The New England Journal of Medicine Evidence analyzed the COVID-19 breakthrough case and death rates among fully vaccinated individuals who were 12 years of age or above based on months of completing the primary COVID-19 vaccine series as a proxy for waning immunity. The current study was conducted during the period when the Delta variant was the dominant circulating strain in the United States.

About the study

The current study included COVID-19 cases and vaccination data from 15 jurisdictions of the United States that included Arizona, Arkansas, Florida, Georgia, Idaho, Indiana, Massachusetts, Michigan, Nebraska, New Jersey, New Mexico, New York City, Tennessee, Utah, and Wisconsin.

All jurisdictions were divided into several regions such as West, Midwest, South, and Northeast. Individuals vaccinated with Ad26.COV2.S vaccine between January to February 2021, as well as all persons 12 to 17 years of age who were vaccinated with either the mRNA-1273 or Ad26.COV2.S vaccines were excluded from the study.

A fully vaccinated person was defined as those who had passed 14 or more days since the completion of the primary series of an FDA authorized COVID-19 vaccine. A breakthrough infection was defined as a SARS-CoV-2 infection in a person who had passed 14 or more days since the completion of the primary series of an FDA-authorized COVID-19 vaccine. A COVID-19 associated death was defined as the death of a person who had been diagnosed with COVID-19 and where COVID-19 was determined to be a vital cause of death.

The vaccine administration data provided weekly counts of vaccinated persons who were stratified according to the Morbidity and Mortality Weekly Report (MMWR) week of completion of the primary vaccine series, age group, vaccine product, and jurisdiction. Finally, person-level vaccination data was combined with COVID-19 cases for fully vaccinated people, while vaccination data corresponding to cases occurring within the MMWR week, vaccine product, and age group were removed to obtain one record for each vaccinated person.

Study findings

The results of the study indicated that across 15 jurisdictions, 411,661 cases, 6322 deaths, and 48,832,299 vaccinated persons were reported from January 3 to September 4, 2021. The overall cases from January 3 to September 4, 2021, were found to be higher among individuals who were 18 to 49 years of age from the Southern region and had received the Ad26.COV2.S vaccine.

The median time required for infection among vaccinated people was reported to be 111 days for the BNT162b2 vaccine, 118 days for the mRNA-1273, and 102 days for the Ad26.COV2.S.

For the Ad26.COV2.S vaccine, peaks in cases were reported at 14 to 42 days after vaccination, as well as at 120 to 160 days. Comparatively, for the other two vaccines, peaks in cases occurred only once at approximately 120 to 160 days. Higher hazardous rates were also observed after July as compared to January to June among the vaccinated cohort due to the emergence of the Delta variant.

The results reported that from August 1 to September 4, 2021, the rate of SARS-CoV-2 infection was highest among individuals with a longer time since vaccination. The overall case rates were reported to be 168.8 among those vaccinated between January and February, 123.5 among those vaccinated between March and April, 83.6 among those vaccinated between May and June, and 63.1 among those who were recently vaccinated in July.

The death rates from January 3 to September 4, 2021, were reported to be quite low across all ages and vaccine products. The death rates were observed to be highest among individuals who were 80 years of age or older, among those who resided in the Southern region of the U.S., and among those who received the Ad26.COV2.S vaccine.

The death rates from August 1 to September 4, 2021, were found to be higher for individuals who had been vaccinated earlier in the year as compared to July. Furthermore, the death rates by age group were found to be higher among those who had received the Ad26.COV2.S vaccine recipients in July.

The current study was, therefore, able to demonstrate that booster doses can reduce the risk of severe SARS-CoV-2 infections, as well as the transmission of variants among all individuals, particularly older individuals. However, vaccinating the unvaccinated population remains a major priority since all vaccines were found to reduce severe disease and death.

Another reason why vaccination of the unvaccinated is of importance is that although waning of protection is observed in the case of vaccination, sustained protection against death remains in vaccinated individuals younger than 65 years of age.


The current study had certain limitations. First, the study was unable to adjust for different testing and prevention behaviors by age and was also unable to account for geographic heterogeneity. Second, the study could not identify reinfections.

Third, earlier vaccination was aimed at older age groups, while the later stages of vaccination were for the general population, thereby suggesting that the earlier results could not be generalized. Fourth, the different databases utilized for the study lacked a common unique identifier.

Finally, the overall rates can be underestimated in the study, as individuals could have tested positive between 0 to 13 days after the primary series.

Journal reference:
  • Paz-Bailey, G., Sternberg, M., Kugeler, K., et al. (2021). Covid-19 Rates by Time since Vaccination during Delta Variant Predominance. NEJM Evidence. doi:10.1056/EVIDoa2100057.
Suchandrima Bhowmik

Written by

Suchandrima Bhowmik

Suchandrima has a Bachelor of Science (B.Sc.) degree in Microbiology and a Master of Science (M.Sc.) degree in Microbiology from the University of Calcutta, India. The study of health and diseases was always very important to her. In addition to Microbiology, she also gained extensive knowledge in Biochemistry, Immunology, Medical Microbiology, Metabolism, and Biotechnology as part of her master's degree.


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