Does the Updated COVID-19 Booster help Protect against Recent SARS-CoV-2 Variants?

We are currently experiencing what appears to be the second-highest COVID-19 wave of infections since the beginning of the pandemic. Some countries, and now one U.S. state, are reporting more hospitalizations for COVID-19 than at any prior time in the pandemic. It is hard to attribute this to any one particular factor, but likely contributing factors are:

1. Waning immunity. The evidence is now clear that immunity wanes over months whether generated by infection, immunization or both, however, fortunately, the protection against severe disease, hospitalization and death does appear to last longer.
2. Low uptake of the updated COVID-19 booster that was released in September 2023. The latest CDC dashboard (as of December 23, 2023) showed that only 18.9% of all adults, shockingly only 11.2% of pregnant women, and only 7.9% of children have received the updated COVID booster.
3. The near abandonment of mitigation measures allowing for high levels of transmission.
4. The emergence of variants with enhanced immune escape. RNA viruses such as SARS-CoV-2 are prone to acquire mutations and the likelihood for consequential mutations increases with increasing transmission. It is very likely that some of the major new variants have arisen from chronic infections in immunocompromised persons, however, there is also growing concern for spillback of infections with more diverse mutations from the enormous range of animals that humans have infected with SARS-CoV-2.
5. Some early reports that show evidence in vitro (in the laboratory) that while the early Omicron variants showed more of a propensity for upper respiratory tract infection, the new globally dominant circulating variant (JN.1) may have developed greater tropism (cells for which the virus has affinity) for the lung. This has created concern (but not proof) that the current circulating variant may have higher likelihood of causing more severe disease. It likely will take a while to determine whether this is the case.

There are many things we can do to protect ourselves from infection, however, immunization has always been foundational to protecting against severe disease if one does become infected. Thus, it is important to examine the effectiveness of the newly updated booster in light of the current variant that has much greater immune escape capabilities than prior variants.

Further, in view of the rapid evolution of variants, it has been concerning to note that even infection has provided protection for a briefer period of time than earlier in the earlier years of the pandemic. For example, an infection with the variant XBB.1.5 which was on a steep rise in the U.S. one year ago, was reported in several studies not to produce the degree of antibody response needed to protect against infections with subsequent variants that developed as off-shoots of this variant. This concern has been heightened in light of recent studies once again confirming that the risks of long-term health consequences (e.g., Long COVID) increase with each infection. That rightly raises the question as to whether the updated booster would then be effective against recent variants.

Investigators just published their findings https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00784-3/fulltext yesterday.

The investigators compared the immune responses to the updated booster in two groups of study participants – one group had no known prior COVID infection and the other group had a confirmed case of COVID with any XBB subvariant prior to receiving the booster. They assessed neutralizing antibody levels prior to vaccination and then 3-4 weeks following the booster dose. Those who had an XBB infection followed by the booster had a statistically significant rise (1.8 – 3.6-fold) in antibody levels against all subvariants tested (XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, HK.3 and BA.2.86 [this latter one being the immediately preceding and closest related variant to the current JN.1]).

Those boosted who had no known prior COVID-19 also had a statistically significant rise (2.1 – 3.9-fold) in antibody levels against all of the same variants. However, some individuals failed to mount an adequate response following their booster dose.

Of note, when antibody levels were tested on the pre-booster samples for both groups, those with recent XBB infection had 5.7 – 10.4-fold higher neutralizing antibody titers against these recent variants compared to those who had never been infected.

What were some of the limitations of this study?

1. The study groups were very small. This limits the confidence that these results are generalizable to the entire population.
2. It is not clear which vaccine brands participants had received, and we cannot be sure that these same results would occur with all three vaccines (Pfizer, Moderna and Novavax). Further, some not previously infected participants had received 5 vaccines prior to the booster, and others 6.
3. It did appear that there was a bias introduced in that some of the not previously infected participants were much older (one was 81 and one was 89) and we know that people of this age group don’t mount as robust an antibody response to almost anything compared to younger individuals.

What should we take away from this study and other recently published studies.

1. It does appear increasingly clear that if you have not had a recent infection or the updated booster this Fall, you likely are more susceptible to infection from the newly predominant variant than those who have.
2. If your last COVID immunization was with the versions of the vaccine prior to the newly updated booster, you likely have much less protection against this new variant than you did against prior variants.
3. We will listen and watch closely as the FDA’s vaccine advisory group meets this year to consider the next formulation of vaccine booster whether they will recommend a new variant serve as the basis for the next booster and whether they will recommend a second dose of the current booster formulation this spring for those with underlying medical conditions, those who are older, and/or those without prior known infection.

For now, get the newly updated booster if you haven’t done so already. As a side note, and I will write about this in an upcoming blog post, the data just recently published shows that kids have a much better and longer lasting immune response from the COVID vaccines than adults!