Where Are We with COVID Boosters?

As we are moving into the Flu season, a raise in infection with a new variant of SARS-CoV-2 is noted. The Food and Drug Administration and the Centers for Disease Control (CDC) have signed off on new COVID vaccine boosters that target the XBB.1.5. Omicron's XBB variant is a recombinant of the previous variants BA2.75 an BJ.1. Overall, XBB variant infection lends to mild-to-moderate symptoms just like previously diagnostic stains. Consequently, vaccine makers have been manufacturing updated vaccines that target XBB variants that include 1.5, EG.5 and FL1.5.1. It is likely that most healthy people will only need one booster until fall 2024. There seems to be little concern about efficacy of the new boosters especially across strains. Interestingly, while it is likely that every year a booster will be recommended much like the flu vaccine, the underlying rational is different. We think more of flu vaccines as strain-matched vaccines as opposed to periodic boosters.

We are not short on variants to think about. Perhaps on the horizon is BA.2.86, nicknamed Pirola, a new omicron sublineage of SARS-CoV-2 that contains many mutations to the spike gene. It was first detected this year in Denmark. ¹ Genomic and surveillance analysis suggests a widespread distribution of BA.2.86 with a high number of mutations conferring what might be considered as having immune-evasive potential. Consequently, the authors suggest that BA.2.86 has the possibility of outcompeting currently dominating variants causing hospitalizations, but not yet. ²

Nearly all the U.S. population has antibodies to SARS-CoV-2 from vaccination, previous infection, or both, and it is probable that these antibodies will continue to provide some protection against severe disease from variants. Vaccines developed so far have consistently shown to provide protection against severe disease, hospitalization, and death. Waning protection is driven by both waning immunity over time since vaccination or initial infection, and the evolution of new variants of SARS-CoV-2. This speaks to durability of the immune response to primary infection agent and its variant variants.^3,4 Yet, the capacity of antibodies to cross neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms. ⁵

While the side effects of updated boosters should be the same as the previous iterations of immunization, with the common side effects that include headache, chills, fever, nausea, and pain or swelling at the injection site, another more subtle viewpoint emerges that is associated with individual benefit analysis relative to potential harm by vaccination. First off, while the CDC indicates on their webpage that basically all individuals starting at age 6 months should be immunized with a COVID-19 vaccine, the United Kingdom defines who is eligible for a seasonal COVID-19 vaccine on an individual's health basis. The U.K. recommendations are well defined from an individual viewpoint. On the other hand, there are suggestions that the U.K. program should be expanded since it leaves a large portion of the Populus inadequately protected against COVID-19. ⁶ It is perceived that this is especially important considering the Long-Covid syndrome. Consequently, messaging is very different between the two countries and with respect to the CDC there is little mention as to why everyone should be immunized.

Second, Risk–Benefit messaging seems a bit confusing. The CDC provides information on their webpage as to various metrics like prevention of hospitalizations, hospital admissions, and death, over several age groups for every million doses of mRNA COVID vaccine. These numbers for example range from like 19–95 hospitalizations for 12–17-year olds for every million doses. However, since Omicron variants seem less severe, a question must be answered very clearly if hospitalizations with Omicron variants is higher than the calculated prevention data. In contrast, reporting rates, for example, of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.73 [95% CI 61.68–81.11] per million doses of the BNT162b2 vaccine) ⁷ suggesting that risk–benefit is not balanced one way or the other.

Alternative viewpoints on risk are out there (Fraiman et al., 2022). ⁸ The CDC could be more helpful in providing detailed severe adverse event number per million doses as they have done for hospitalization metrics. In this way, there could be very clear messaging as to why individuals should be vaccinated to encourage vaccine compliance as opposed to mandates which occurred during the pandemic.