A game-changing study carried out by the prestigious Cleveland Clinic, ranked as the second-best hospital globally, has uncovered a striking correlation: the more COVID-19 vaccine doses a person receives, the higher their risk of contracting the virus.
The research, conducted with a large sample size within the healthcare system, capitalized on the early recognition of the need to maintain an effective workforce during the pandemic.
Participants in the trial were all Cleveland Clinic Health System employees working at any Cleveland Clinic facility in Ohio on September 12, 2022, the first day the bivalent vaccine was made accessible to staff.
The study, which has undergone peer review and has been published, stated:
“The risk of COVID-19 also varied by the number of COVID-19 vaccine doses previously received. The higher the number of vaccines previously received, the higher the risk of contracting COVID-19.”
Furthermore, the study found that the bivalent vaccines demonstrated an overall effectiveness of about 29% in protecting against infection with SARS-CoV-2 when the Omicron BA.4/5 lineages were the predominant circulating strains. Only 29%. However, this effectiveness decreased when the circulating strains were no longer represented in the vaccine. In the case of the XBB lineages, the study could not establish a significant protective effect.
“The multivariable analysis also found that the more recent the last prior COVID-19 episode was, the lower the risk of COVID-19, and the greater the number of vaccine doses previously received, the higher the risk of COVID-19,” according to the study.
Here’s a deeper dive into the study’s findings:
The association of increased risk of COVID-19 with more prior vaccine doses was unexpected. A simplistic explanation might be that those who received more doses were more likely to be individuals at higher risk of COVID-19. A small proportion of individuals may have fit this description. However, the majority of participants in this study were young, and all were eligible to have received ≥3 doses of vaccine by the study start date, which they had every opportunity to do.
Therefore, those who received <3 doses (46% of individuals in the study) were not ineligible to receive the vaccine but rather chose not to follow the CDC’s recommendations on remaining updated with COVID-19 vaccination, and one could reasonably expect these individuals to have been more likely to exhibit risk-taking behavior. Despite this, their risk of acquiring COVID-19 was lower than that of participants those who received more prior vaccine doses.
Ours is not the only study to find a possible association with more prior vaccine doses and higher risk of COVID-19. During an Omicron wave in Iceland, individuals who had previously received ≥2 doses were found to have a higher odds of reinfection than those who had received <2 doses, in an unadjusted analysis.
A large study found, in an adjusted analysis, that those who had an Omicron variant infection after previously receiving 3 doses of vaccine had a higher risk of reinfection than those who had an Omicron variant infection after previously receiving 2 doses.
Another study found, in multivariable analysis, that receipt of 2 or 3 doses of am mRNA vaccine following prior COVID-19 was associated with a higher risk of reinfection than receipt of a single dose.
Immune imprinting from prior exposure to different antigens in a prior vaccine and class switch toward noninflammatory spike-specific immunoglobulin G4 antibodies after repeated SARS-CoV-2 mRNA vaccination have been suggested as possible mechanisms whereby prior vaccine may provide less protection than expected.