Third Dose Prevents Infection

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Science-Based Medicine

Steven Novella on November 3, 2021

The evidence is in. Booster shots work.

We seem to be on the other side of the delta wave of the COVID-19 pandemic, but the pandemic overall is far from over. The world has just surpassed 5 million dead from the illness, although the true number, especially if we consider all downstream consequences, is likely much higher. We have probably not seen the last of new variants. Expert opinion seems to be moving in the direction that it is likely COVID-19 will become endemic, like the flu, that we will have to deal with chronically.

The good news, of course, is that we have many highly effective vaccines. This good news is mitigated by irrational anti-vaccine propaganda, and we will have to keep up the fight against that as well. There is also a little bit of a debate about how necessary a third dose or booster shot is, and if countries with early vaccination programs should be prioritizing boosters or getting the rest of the world vaccinated. The official US position is that we will do both, with a pledge of 1 billion doses donated in 2022.

Some recent evidence helps inform this decision, confirming the effectiveness of a third dose for those vaccines that originally required two doses. One study, published recently in The Lancet, is the largest observational study of vaccine effectiveness for COVID-19 to date. The study is based on a large public dataset from Israel, which was one of the earliest countries to achieve high levels of vaccination. The study had two arms, those who had received a third dose of the Pfizer-BioNTech vaccine at least 7 days prior, and those who had received only two doses with the second dose at least 5 months prior. Each arm had 728,321 demographically matched individuals. The observational period, from July 30, 2020 to Sept 23, 2021, was during a wave dominated by the delta variant.

The study found that, compared to those who received two doses, there was a 93% decrease in infections, a 95% decrease in hospitalizations, a 92% decrease in severe disease, and an 81% decrease on COVID-related deaths. The study also included a population-level evaluation. They found that 7-10 days following each age group becoming eligible for a third dose, infection rates began to drop in that age group. This is overall impressive vaccine efficacy, and remarkable when compared to those with only two doses at least five months earlier. This is strong evidence in favor of giving a third dose.

Another study out of Oxford, currently in preprint, looked at rated of transmission with both the alpha variant and delta variant following two doses of either the Pfizer-BioNTech vaccine or the AstraZeneca vaccine. This is a retrospective cohort study looking at contact tracing for those with positive tests for COVID-19, comparing the fully vaccinated (two doses) with unvaccinated individuals. They found that the Pfizer vaccine reduced transmission of the alpha variant with an odds ratio of 0.18, while AstraZeneca had an odds ratio of 0.37. For the delta variant the numbers were 0.35 and 0.64 respectively.

Therefore, both vaccines reduced the chances of spreading COVID-19 (not just getting it), although not as much for the delta variant. They also found that this risk reduction waned over time, giving more evidence in support of a third dose.

Until recently scientists for organizations like the CDC were saying that the evidence for the need of a third dose is “weak”. Early evidence was based entirely on antibody titers, with studies showing that these titers do decrease over time from completion of vaccination. However, it was not clear whether these declining antibody levels would translate to decreased clinical effectiveness. Of course, it was both highly plausible and anticipated that titers and immunity would correlate, but scientists were being honest in saying that we did not know for sure. This was also happening during the most recent wave of the pandemic dominated by the delta variant. In the face of spiking case numbers and waning antibody numbers, many countries opted for booster shots.

Now we have good data that this calculated expense paid off. Giving a third dose or booster shot of any of the COVID-vaccines reduces the risk of getting infected, getting a severe illness, being hospitalized, and dying. Further, it reduces the chance of passing the illness along to contacts, probably from reduced viral loads (although this does not explain all of the reduction in risk of transmission). In light of this there is now a very strong case to be made for offering booster shots, and anyone eligible should avail themselves of the extra immunity.

The benefits are both individual and societal. The individual benefits are obvious from the numbers above – reduced risk of dying is a huge benefit. But even for those who would not have died, severe illness and hospitalization results in significant morbidity and the possibility of long COVID with significant reduction in quality of life and productivity.

Further, getting fully vaccinated clearly protects those around you. The flip side of this is that failing to get vaccinated puts your family and friends at unnecessary risk. At the societal level, reducing transmission and infection rates is the best way of bringing this pandemic under control (even if it does become endemic). Reduced infections will reduce the probability of new variants emerging, that could spawn entirely new waves of illness. Reducing hospitalizations has a profound effect on the use of hospital resources, including front-line workers. This is one of the hard-to-quantify results of the pandemic, those who suffered because they could not get their elective surgery, or who avoided the ER or could not get an ICU bed because of COVID patients.

In the middle of a pandemic like COVID, individual decisions affect everyone.