Cleveland Clinic Bombshell 48.2K Healthcare Employee Study—The More Doses with COVID-19 mRNA Vaccine, the Higher the Infection Risk

Nabin Shrestha, MD, MPH, infectious disease staff physician, and colleagues at Cleveland Clinic have been conducting ongoing research involving healthcare workers during the COVID-19 pandemic. In past studies they found the possibility that the more participants were vaccinated with mRNA COVID-19 vaccines the more susceptible they were in some cases to infection. In this latest investigation published in the peer-reviewed journal Clinical Infectious Diseases, the Cleveland Clinic team studies the overall ability of the COVID-19 mRNA vaccine to protect against COVID-19. Again, monitoring employee participants involving vaccination with the 2023–2024 formulation of the COVID-19 mRNA vaccines, the authors prospectively examined cumulative incidence of COVID-19 over the following 17 weeks. Analyzing as a time-dependent covariate actual protection afforded by COVID-19 mRNA vaccination, the Cleveland Clinic physician-investigators utilized Cox proportional hazards regression, with time-dependent coefficients separating effects before and after the JN.1 lineage became dominant. Dr. Shrestha and colleagues also adjusted for the propensity to get tested, age, sex, the pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses as key variables. What were the findings? The Cleveland Clinic concluded the working-age adults employed at Cleveland Clinic and participating in this study were afforded modest protection at best with the 2023-2024 COVID-19 mRNA formula prior to the predominant circulation of JN.1, and not very good protection thereafter. TrialSite has chronicled this study group and their findings, and now the outcomes are yet again validated—risk for COVID-19 infection rises with the number of mRNA COVID-19 vaccine doses.

The Findings

Involving 48 210 Cleveland Clinic employees, the study’s authors report a total of 2462 (5.1%) COVID-19 cases during the 17 weeks of observation. When calculating the multivariable analysis, Dr. Shrestha and team report the 2023-2024 formula vaccinated state was associated with a significantly lower risk of COVID-19 before the JN.1 lineage became dominant (hazard ratio = .58; 95% confidence interval [CI] = .49–.68; P < .001), and lower risk but one that did not reach statistical significance after (hazard ratio = .81; 95% CI = .65–1.01; P = .06).

Cleveland Clinic

Source: Cleveland Clinic

With an estimated vaccine effectiveness of 42% (95% CI = 32–51) prior to the JN.1 lineage emerging as predominant, this number precipitously dropped to 19% (95% CI = −1–35) after, even going into negative territory like with previous studies.

Not surprisingly, persons who were previously infected with an XBB or more recent strain of SARS-CoV-2 faced a lower risk of infection. As with previous studies, the risk of COVID-19 infection “increased with the number of vaccine doses previously received.”

This latest study, now peer-reviewed and published in a reputable journal (previous studies were only preprint), leads to what TrialSite describes as a bombshell revelation that should not be ignored.

Limitations

The study, like all observational studies, this one must be understood in the context of constraints. Although the group has been studying this large cohort of healthcare employees throughout the pandemic, a major assumption of the Cox proportional hazards model, for example, is that the effect of a given covariate does not change over time. The study does not establish causation but does show association.

Nabin K Shrestha, MD, MPH, Corresponding Author

Lead Research/Investigator

• Nabin K Shrestha, MD, MPH, Corresponding Author
• Patrick C Burke, Infection Prevention
• Amy S Nowacki, PhD, Quantitative Health Sciences
• Steven M Gordon, MD, Infectious Diseases

Call to Action: TrialSite recommends purchase of the study.