Odds of Positive Test Results for COVID After BNT162b2 Booster
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
With the evidence of waning immunity of the mRNA vaccine BNT162b2 (Pfizer-BioNTech), a nationwide third-dose (booster) vaccination campaign was initiated in Israel during August 2021; other countries have begun to administer a booster shot as well.
Objective
To evaluate the initial short-term additional benefit of a 3-dose vs a 2-dose regimen against infection of SARS-CoV-2.
Design, Setting, and Participants
This preliminary retrospective case-control study used 2 complementary approaches: a test-negative design and a matched case-control design. Participants were included from the national centralized database of Maccabi Healthcare Services, an Israeli healthcare maintenance organization covering 2.5 million members. Data were collected between March 1, 2020, and October 4, 2021, and analyses focused on the period from August 1, 2021, to October 4, 2021, because the booster dose was widely administered from August 1 onward.
Exposures
Either 2 doses or 3 doses of the BNT162b2 vaccine.
Main Outcomes and Measures
The reduction in the odds of a positive SARS-CoV-2 polymerase chain reaction (PCR) test at different time intervals following receipt of the booster dose (0-6, 7-13, 14-20, 21-27, and 28-65 days) compared with receiving only 2 doses.
Results
The study population included 306 710 members of Maccabi Healthcare Services who were 40 years and older (55% female) and received either 2 or 3 doses of the BNT162b2 vaccine and did not have a positive PCR test result for SARS-CoV-2 prior to the start of the follow-up period. During this period, there were 500 232 PCR tests performed, 227 380 among those who received 2 doses and 272 852 among those who received 3 doses, with 14 989 (6.6%) and 4941 (1.8%) positive test results in each group, respectively. Comparing those who received a booster and those who received 2 doses, there was an estimated odds ratio of 0.14 (95% CI, 0.13-0.15) 28 to 65 days following receipt of the booster (86% reduction in the odds of testing positive for SARS-CoV-2).
Conclusion and Relevance
Previous studies have demonstrated that vaccine-derived protection against SARS-CoV-2 wanes over time. In this case-control analysis, we showed an association between receipt of the booster dose and a reduction in the odds of testing positive for SARS-CoV-2, potentially counteracting waning immunity in the short term. Further monitoring of data from this population is needed to determine the duration of immunity following the booster.
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Additional Info
Disclosure statements are available on the authors' profiles:
Odds of Testing Positive for SARS-CoV-2 Following Receipt of 3 vs 2 Doses of the BNT162b2 mRNA Vaccine
JAMA Intern Med 2021 Nov 30;[EPub Ahead of Print], T Patalon, S Gazit, VE Pitzer, O Prunas, JL Warren, DM WeinbergerFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The third shot – is it useful?
With the world in a panic about Omicron, there is a sense of doom and gloom. A virus with many new mutations, which spreads quickly and could evade our antibodies. Unfortunately, the hope of an Omicron-specific vaccine is at least 4 months away. So, what is the game plan? The traditional mask, distance, and good ventilation will still work. But what about vaccines? Could we give a third shot of the current vaccine which is not an Omicron-specific one and still get protection against Omicron? Obviously, we don’t have the answer to that yet. We will have to watch and see what happens in countries like Israel where there are a significant number of people with 3 shots.
However, we can look at what happened with the Delta variant and speculate if the same thing will happen with Omicron. Remember that we do not have a Delta-specific vaccine. The vaccines we are using now were based on the first spike protein mutation (D614G), which had dominated the world at the beginning of the pandemic. This vaccine, based on this old spike protein, has helped us deal with Alpha, Beta, Gamma and currently the dominant Delta variant. So, can we give a third shot of a non-Delta vaccine and still get better protection? If the answer is yes, then maybe the same will be true with Omicron.
Israel has been leading the world in vaccinations. They were the first to give boosters en masse to their population. These two studies from Israel tell us what happens when you give 3 shots of a non-Delta vaccine – was there increased protection against the Delta variant?
The first study looked at whether a third shot of the original vaccine could reduce hospitalization and death. They used the database from Clalit Health Services, which looks after half of the population in Israel. They matched up patients who had 3 doses to patients who had 2 doses.
For admission to hospital, there was a reduction of 93% (231 vs 29 events; 95% CI, 88–97) in favor of 3 doses. For severe disease, the reduction was 92% (157 vs 17 events; 95% CI, 82–97). For COVID-19 related death, the reduction was 81% (44 vs 7 events; 95% CI, 59–97). This clearly shows that a non–variant-specific vaccine given as a third dose can provide profound protection.
That was the prevention of invasive COVID disease, but what about just getting the virus? One of the issues with Delta and with Omicron is that fully vaccinated people could pick up and grow the virus in their nasal passages, which means that they can spread the virus to others. So, preventing them from getting the virus would be critical in stopping the spread.
To answer this question, this second study looked at PCR tests in patients with 3 shots versus 2 shots. They used the data from the Maccabi Healthcare Services. During the study period, there were 500,232 PCR tests performed. There were 227,380 PCR tests done on patients who had 2 doses and there were 272,852 PCR tests done in those who had 3 doses.
With this large database, they showed that the 2-dose patients had 14,989 positive tests, which is 6.6%. On the other hand, the 3-dose patients had 4941 positive tests, which is only 1.8%. Therefore, we can infer that the third shot was able to reduce infection rates as well. This means that fewer vaccinated people were carrying the virus in their nose, and hence, less likely to spread it to others.
Both of these studies were done when Delta was the main variant. Therefore, these two studies showed that giving a non–delta-specific vaccine was able to reduce infection by Delta and protect against hospitalization and death. This gives us hope that a third shot might also be useful against Omicron.
There are many possible explanations for this, but two of them seems to make the most sense. The first is that we don’t make just one antibody to the spike protein, we make a few that target different parts of the spike protein. Although Omicron has 30 mutations on the spike protein, there are still many that are the same as the original spike protein. With each shot, we get a chance to produce antibodies that target those common areas. That might be why a non-Delta vaccine can give such good protection.
Another explanation has to do with our T cells. The T cells are boosted up every time we get a shot. These T cells can differentiate into T killer (CD8+ cytotoxic) cells which could recognize and destroy Delta- or Omicron-infected cells. The T cells that differentiate into T helper cells (CD4+) could direct the army towards the Delta or Omicron virus despite their mutations. These T cells would do their job even if the spike proteins looked a bit different from one virus to the next.
The bottom line is that these two studies show us that a non–variant-specific vaccine could still be useful. This gives us great hope that with a third shot, we could protect the world from Omicron or whatever “cron” might be coming in the future. Also, if the concept of attacking the common part of the virus holds up, then maybe we don’t need a shot for every single mutation and the future is hopeful again.