In a compelling counter-narrative to prevailing views on COVID-19 immunization, a recent study from the Cleveland Clinic Health System reveals that individuals not considered “up-to-date” with their COVID-19 vaccinations, as per the Centers for Disease Control’s (CDC) definition, may have a lower risk of contracting the virus compared to their “up-to-date” counterparts.
This unexpected finding emerges as the dominant XBB lineages of the virus circulate, leading researchers to question the efficacy of bivalent vaccines against these new variants and the existing CDC guidelines for determining vaccination adequacy.
The research in question is a retrospective cohort study carried out at the Cleveland Clinic Health System (CCHS), dating back to January 23, 2023. The point of reference was when the XBB lineages became the dominant strains in Ohio. It concentrated on CCHS employees, specifically those present when the XBB lineages took center stage.
The study’s fundamental outcome was time to COVID-19, defined as the time it took for a positive SARS-CoV-2 test result to emerge. The subjects were under close observation until May 10, 2023, facilitating an evaluation period of 100 days from the study’s onset.
The study included 48,344 participants, from which 1,445 were omitted due to employment termination. By the study’s conclusion, 12,841 participants were “up-to-date” with their COVID-19 vaccination. Most received the Pfizer vaccine, while a smaller group was administered the Moderna vaccine. Over the study period, 1,475 employees tested positive for SARS-CoV-2.
Participants were relatively young, with an average age of 43 years. Around 46 percent had previous COVID-19 history, and the Omicron variant infected 34 percent. Notably, 87 percent of the study population received at least one vaccine dose, and 92 percent had been exposed to SARS-CoV-2 either via vaccination or infection.
The study concluded that the risk of contracting COVID-19 was 23 percent lower in the “not up-to-date” group as compared to their “up-to-date” counterparts. The study found no apparent difference in COVID-19 risk between the two groups when stratified by the most recent infection date.
According to the study authors, “There are two reasons why not being “up-to-date” on COVID-19 vaccination by the CDC definition was associated with a lower risk of COVID-19.”
Firstly, the efficacy of the bivalent vaccine against the XBB lineages of the Omicron variant was lower than anticipated. COVID-19 vaccines were designed to target the spike protein of the virus. As new variants emerge, changes to this spike protein may reduce the effectiveness of vaccines, which appears to be the case with the XBB lineages.
Secondly, the CDC’s definition of “up-to-date” may not fully account for the immunity gained from previous COVID-19 infections. Research indicates that individuals who have recovered from a SARS-CoV-2 infection develop robust immunity.
A 2023 study published in The Lancet reports, “Although protection from past infection wanes over time, the level of protection against re-infection, symptomatic disease, and severe disease appears to be at least as durable, if not more so, than that provided by two-dose vaccination with the mRNA vaccines for ancestral, alpha, delta, and omicron BA.1 variants.”
There were limitations of the current study. The demographic consisted primarily of relatively young healthcare workers who might have better health behavior and access to medical resources.
The study did not consider the varying levels of exposure to the virus in different job roles or the individual’s health status, which could affect the risk of infection. Moreover, the study observed the participants for only 100 days, a relatively short period.
COVID-19, caused by the SARS-CoV-2 virus, has spawned numerous variants since the pandemic’s onset in November 2019. Notably, the Omicron variant and its potent subvariants, like the XBB lineages, have proven dominant, thanks to their genetic mutations, which allow for enhanced transmissibility.
The Omicron saga began with the initial strain (BA.1), first identified in Botswana and South Africa in November 2021. It proliferated rapidly, sending U.S. daily case numbers soaring into the millions by December of that year. As 2022 dawned, omicron generated several subvariants, cementing its place as the predominant SARS-CoV-2 strain in the U.S. By January 2023, a new subvariant, XBB.1.5, was leading the pack in U.S. infections.
“Viruses constantly change through mutation and sometimes these mutations result in a new variant of the virus,” the CDC explains. “Some changes and mutations allow the virus to spread more easily or make it resistant to treatments or vaccines. As the virus spreads, it may change and become harder to stop.”
To navigate this shifting landscape, understanding vaccines is paramount. Many COVID-19 vaccines, such as Pfizer and Moderna, utilize mRNA technology. They instruct our cells to produce a piece of the spike protein found on the SARS-CoV-2 virus surface, initiating an immune response.
In contrast, a bivalent vaccine is engineered to guard against two separate virus strains. In the context of COVID-19, the vaccine targets two distinct SARS-CoV-2 variants, attempting to provide broader protection.
“The bivalent booster is the most recent version of the COVID-19 vaccine. It contains both the original vaccine strain [of the virus] and a strain derived from the BA.5 omicron variant, which is currently dominating here in the U.S.,” reports the Johns Hopkins Bloomberg School of Public Health.”
However, as the study underlines, the efficacy of such a multi-target approach may vary as viral strains evolve.
The narrative of COVID-19 vaccines has been a tumultuous ride since their first FDA Emergency Use Authorization in December 2020. The pandemic’s dynamic nature and changing knowledge about the virus led to a sequence of evolving recommendations throughout 2021 and 2022.
Grappling with different viral variants and fluctuating infection rates, the FDA recommended boosters in September 2021. These recommendations kept adapting in an effort to tailor to various age groups and risk profiles.
By August 2022, the FDA had broadened the vaccine playing field by authorizing bivalent vaccines as a single booster dose two months post the initial vaccination. The next day, the CDC endorsed the first update for the bivalent COVID-19 booster.
By April 2023, the CDC further refined its guidance. To be considered “up-to-date” with COVID-19 vaccination, individuals over the age of six now needed at least one dose of a COVID-19 bivalent vaccine. This relentless evolution of guidelines encapsulates the struggle to stay current with a virus that has been anything but static.
According to the American Medical Association (AMA), as of May 2023, very few Americans have received the bivalent booster. “Overall, only 16.7 percent of the U.S. population has received a dose of the updated booster. And only about 43 percent of those 65 and older have received the bivalent booster,” said AMA Board Chair, liaison to the Advisory Committee on Immunization Practices (ACIP), and member of ACIP’s COVID-19 Vaccine Workgroup, Sandra Adamson Fryhofer, MD.
In a win for vaccine makers this week, the FDA recommended that COVID manufacturers make a single-strain vaccine for the upcoming fall that targets the XBB.1.5 omicron subvariant, a task they’d already been working on.
“Based on the totality of the evidence, FDA has advised manufacturers who will be updating their COVID-19 vaccines, that they should develop vaccines with a monovalent XBB 1.5 composition,” the FDA said in a release. This new recommendation would shift away from the bivalent booster, although the timing has yet to be determined.