In a recent study published in Nature Communications, a team of researchers from Israel conducted a retrospective analysis of the severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) reverse transcriptase – quantitative polymerase chain reaction (RT- qPCR) test measurements.

Study: Waning of SARS-CoV-2 booster viral-load reduction effectiveness. Image Credit: Studio Romantic/Shutterstock

The researchers determined the association of the Pfizer/BioNTech BNT162b2 coronavirus disease 2019 (COVID-19) booster vaccine with reduced viral load over time during the SARS-CoV-2 Delta-variant-dominant period in Israel.

The Pfizer/BioNTech BNT162b2 COVID-19 vaccine is highly effective in the prevention of infection and reducing the viral loads of breakthrough infections (BTIs). Recently, various studies have shown that the effectiveness of SARS-CoV-2 vaccines declines mildly in preventing COVID-19-related severeness, while the vaccine effectiveness declines strongly in the protection against infection and for reducing viral loads in BTIs. However, COVID-19 boosters or third dose administration was linked to the re-establishment of lost effectiveness against infection and reduction of viral loads in BTIs.

The duration for which the regained effectiveness of the COVID-19 booster vaccine will last, and the requirement of supplementary COVID-19 booster vaccine shots in the future is unknown. To fill this gap, the present study is designed to monitor the effectiveness of the BNT162b2 vaccine booster dose with time in reducing the viral load.

Study design

In the current study, the researchers retrieved cycle threshold (Ct) values of SARS-CoV-2 RT-qPCR tests of all COVID-19-positive patients tested at the Maccabi Healthcare Services (MHS) Central Laboratory from 28 June, 2021, to 29, November, 2021. Patient parameters like sex, birth year, COVID-19-induced hospitalization, and baseline immunosuppression condition were collected.

MHS centralized database was accessed for gathering COVID-19 vaccination data of patients. Nasopharyngeal swab samples of patients were collected and Ct values for three SARS-CoV-2 genes – envelope (E), nucleocapsid (N), and ribonucleic acid (RNA)-dependent RNA polymerase (RdRp) genes – and the internal control for each test were estimated by Seegene software for the Allplex 2019- Ncov assay.

Linear regression of the untransformed Ct values for each of the three viral genes was calculated as a function of time, sex, age, calendric date, and a quadratic variable of calendric date. Regression models were implemented through the Python statsmodels library and scipy library.

The researchers calculated the change in Ct values in post-vaccination time bins by applying a linear regression model. Log transformation of Ct values was performed to calculate the viral load reduction factor. The researchers fitted the exponential decline model with the Ct data to estimate the decay rate. Statistical confidence intervals (CIs) were estimated by bootstrapping with restricting bounds.


The findings of the study demonstrated 5,229 infections in unvaccinated individuals, 16,038 BTIs in COVID-19 second-dose-vaccinated individuals, and 1,390 BTIs in COVID-19 booster-dose-vaccinated individuals.

Multivariable linear regression analysis demonstrated that COVID-19 second dose-vaccinated individuals showed Ct regression coefficients of 4.2 for BTIs, post 7-30 days of second-vaccine dose compared to unvaccinated individuals. The regression coefficient decayed over time and vanished at six months or longer post-vaccination (for RdRP, N, and E gene).

COVID-19 booster vaccination increased Ct value by 2.7 for BTIs post 7-30 days of booster dose which corresponded to a six-fold decrease in the viral load. However, the effectiveness of the booster vaccine in reducing the viral load for BTIs declined rapidly to 1.3 and 0.8 post 31-60 days and 61-120 days of a booster dose, respectively.

The researchers applied the time differential model and observed a difference of 2.6 and 1.4 between the Ct values of infections in the first (7-30 days) and second (31-60 days) time bins, post-second dose and booster dose, respectively. These differences corresponded to a similar reduction in Ct values within a month by 62% and 52% post second and booster dose, respectively.


This study demonstrated the rapid waning of the effectiveness of the SARS-CoV-2 BNT162b2 mRNA booster vaccine in reducing viral loads within months post booster dose administration. The rate and magnitude of the reduction in the vaccine effectiveness post-booster dose mirrored the decline observed post-second vaccination dose. This decline in the effectiveness of booster dose possibly affects the community-level transmission of the SARS-CoV-2.

However, this research work has limitations in that the correlation between viral loads and transmissibility was not developed. The study has a probability of biased results due to the variations in health-seeking behaviors of patients that affect the timings of the COVID-19 test. Moreover, the estimation of waning was based on Ct value differences in the vaccinated individuals that probably canceled out some health-seeking biases.

Lastly, the study only considered the SARS-CoV-2 Delta-variant-dominant period, and additional data to understand the waning immunity during the dominance of the SARS-CoV-2 Omicron variant are needed.

The researchers warrant the need to consider the long-term effectiveness of the BNT162b2 mRNA vaccine and further studies to explore the probability of benefits and anticipated duration of protection provided by the additional booster dose.


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