Several vaccines have been rapidly developed to help control the COVID-19 pandemic, including the BNT162b2 vaccine (Pfizer/BioNTech). This severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has been shown in both clinical trials and in the real world to be highly efficacious in preventing infection, symptoms, hospitalizations, severe disease, and death related to coronavirus disease (COVID-19).
Also, previous research has demonstrated a reduction in breakthrough infections due to the BNT162b2 vaccine. Following the national vaccination campaigns that occurred globally, there was a significant reduction in new SARS-CoV-2 infections, which led to hopes of herd immunity and disease eradication. For example, in Israel, almost no new cases of COVID-19 were detected following their vaccine campaign from April to June 2021.
However, there has been a surge of new SARS-CoV-2 infections within highly vaccinated countries, including Israel. This recent surge in infection rate is occurring alongside the global spread of the SARS-CoV-2 Delta variant and possible diminishing vaccine-induced immune response, raising questions of vaccine effectiveness (VE) against the Delta variant over time. Recent studies have shown that VE against infection begins to decline six months post-vaccination. Although, protection against severe COVID-19-related complications appears to be sustained.
A team of researchers from various institutions within Israel performed a retrospective analysis on reverse transcription-quantitative polymerase chain reaction (RT-qPCR) test measurements of three SARS-CoV-2 genes (E, N, and RdRp) from laboratory-confirmed positive tests collected from patients from Maccabi Healthcare Services. This study focussed infections in adults over the age of twenty between 28 June and 9 September 2021, when the Delta variant was the most prominent strain in Israel.
This study is available as a Brief Communication in the Nature Medicine journal.
The study
This study demonstrates that the BNT162b2 vaccine is initially effective in reducing the viral load of Delta variant breakthrough infections with a magnitude of ten-fold, which is consistent with initial effectiveness against the other variants. However, the VE against viral load reduces with time after vaccination, significantly declining three months post-vaccination and almost disappearing six months post-vaccination.
In Israel, as the Delta variant emerged, a large proportion of the population who were vaccinated were past the two-month post-vaccination period, so the population-wide average effect of the BNT162b2 vaccine on the viral load of the Delta variant was negligible, which explains the reports of no difference in cycle threshold (Ct) value between vaccinated and unvaccinated individuals. The authors discovered with the utilization of a booster vaccination, it is possible to regain viral load reduction even against the Delta variant, suggesting the restoration of vaccine-associated mitigation of transmissibility.
These results collectively suggest that the VE in reducing viral loads of the Delta variant breakthrough infections is similar to its observed effectiveness in previous non-Delta surges. The vaccine's efficacy is diminished from the time of initial vaccination but can be restored via a third booster inoculation.
There were several limitations associated with the study. Firstly, although the viral load is a typical indicator of infectiousness, a positive PCR test does not always mean a viable virus is present, and a relationship between infectiousness and viral load is yet to be established. Secondly, results from recent studies suggest that vaccinated individuals display a faster decline in viral load when compared to unvaccinated, which can have a differentiation effect on Ct values for samples taken an extended time after the onset of symptoms.
Therefore, it is also possible that differences in Ct values between the vaccinated and unvaccinated individuals is not only a representation of an initial difference in viral loads but also a difference in viral load decay among the two groups. Thirdly, the authors did not know the number of asymptomatic and symptomatic cases within the study, and it is a possibility that the proportion of symptomatic cases within the unvaccinated could be much higher.
Implications
It remains unknown the length of time of the booster vaccine's renewed effect on the reduction of breakthrough infections and whether additional booster doses will be needed in the future against the variants that are present now or new emerging variants.
Moreover, VE against severe infections may diminish at varying time scales and could be affected differently by booster vaccines. However, to date, there has only been a slight decline observed in preventing severe COVID-19. However, the lower viral load observed in booster-vaccinated Delta breakthrough infections indicates a reduction in infectiousness, which means if this is accompanied by other precautions such as mask-wearing, it could help control the spread of the pandemic.
Levine-Tiefenbrun, M., Yelin, I., Alapi, H. et al. Viral loads of Delta-variant SARS-CoV-2 breakthrough infections after vaccination and booster with BNT162b2. Nat Med (2021). https://doi.org/10.1038/s41591-021-01575-4
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