Estimating SARS-CoV-2 breakthrough infection numbers in the US

By Bhavana KunkalikarMar 16 2022Reviewed by Aimee Molineux

A recent study published in the PLOS One journal estimated the number of symptomatic coronavirus disease 2019 (COVID-19) breakthrough infections in vaccinated individuals in the US.

To date, the US Food and Drug Administration (FDA) has approved three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines for use in the US, namely, the Janssen (Ad.26.COV2.S), Moderna (mRNA-1273), and Pfizer-BioNTech (BNT162b2 mRNA) vaccines. However, with emerging reports of breakthrough infections, estimating the number of SARS-CoV-2 infections in vaccinated individuals can prove crucial.  

About the study

The present study evaluated the number of expected breakthrough SARS-CoV-2 infections in vaccinated individuals in the US, based on existing vaccine efficacy (VE) data, percentage of fully vaccinated populations, and the reported number of COVID-19 cases.

The researchers developed a tool to estimate the probable number of symptomatic SARS-CoV-2 infections among vaccinated people per day in the US using available COVID-19 data. The tool used information including the seven-day average of daily COVID-19 cases reported in the US by the Centers for Disease Control and Prevention (CDC), the aggregate number of individuals fully vaccinated with each approved vaccine, and the VE data of the three approved vaccines.

Breakthrough cases were established as infections observed in individuals 14 days or more post completion of primary vaccination series with an approved COVID-19 vaccine. The average VE of the Moderna and Pfizer-BioNTech vaccines were 94.6%, while that for the Janssen vaccine was 66.9%. For vaccinations administered from January 2021 to May 2021, the calculations were performed using the data of individuals aged 18 years and above while vaccinations post-May 2021 considered calculations for persons aged 12 years or more.

The team calculated the average daily number of SARS-CoV-2 cases observed among individuals eligible for vaccine administration and the proportion of vaccinated individuals among the vaccine eligible population. The number of individuals vaccinated with the Moderna or Pfizer-BioNTech vaccines was estimated using the difference between the total number of vaccinated individuals and the number of Janssen vaccinees.       

The sum total of symptomatic vaccine breakthrough cases expected daily was determined using vaccination coverage in the population and the VE. This was calculated 14 days after the two-vaccine dose series was completed in the US. Weekly estimates and cumulative expected infection count to date were also estimated.

Results

The study results showed that 87.4% of the COVID-19 cases in the US as of the end of July 2021 were observed in persons aged 18 years and above, while 93.7% of the infections were in individuals aged 12 years and above. 

Almost 12 million SARS-CoV-2 cases were observed in the US from January 2021 to July 2021. The average number of daily cases was nearly 210,000 in mid-January and almost 12,000 in late June. On the other hand, the number of symptomatic vaccine breakthrough infections was approximately two per day in January and almost 5000 per day in late July.

In late July, the sum total of symptomatic vaccine breakthrough cases was 198,840 among the 156 million fully vaccinated individuals. From February, the average total of vaccine breakthrough cases escalated by 37% each week, with a slower pace emerging in late April. However, as the spread of the SARS-CoV-2 Delta variant increased in late June, the total symptomatic vaccine breakthrough cases also surged with almost 127 vaccine breakthrough cases reported per 100,000 fully vaccinated individuals.

The researchers found that under different hypothetical scenarios such as doubling the daily average case numbers and assuming VE of all vaccinations as 67%, the number of expected vaccine breakthrough infections varied significantly. The expected vaccine breakthrough cases were proportional to the number of COVID-19 cases and were significantly influenced by VE. In a hypothetical scenario with all VE at 67%, the expected symptomatic breakthrough infection numbers nearly quadrupled without any change in other parameters.

Conclusion

The study findings showed that amid the ongoing scenario of community transmission of SARS-CoV-2 variants along with mass vaccination, vaccine breakthrough infections will likely continue to accumulate.

However, the study showed that the number of infections and related hospitalizations and deaths prevented in vaccinated individuals will exceed the number of vaccine breakthrough infections.