Based in Ohio, USA, Cleveland Clinic is considered a leader in clinical research, education and care. With tens of thousands of employees, they are uniquely placed to investigate outcomes of staff vaccination policy including covid and influenza vaccine mandates.
In 2022, Cleveland Clinic researchers led by Dr. Nabin Shrestha and Dr. Steven Gordon at the Department of Infectious Diseases followed over 51,000 employees. They found that the proportional risk for covid infection increased with the number of covid vaccine doses an individual received.
This is known as negative efficacy and can be due to a multitude of factors, including but not limited to:
- the fact that RNA viruses (including coronaviruses and influenza) mutate rapidly, rendering vaccines targeting prior strains useless. This is known as immune imprinting, or “original antigenic sin”;
- immune suppression caused by persistence of circulating covid vaccine-induced spike protein can increase the risk of infection as well as other immune-related disorders;
- repeated exposure to vaccine-induced spike protein can result in antibodies switching from protective IgG1, IgG2 and IgG3, to the less protective and immune-suppressing IgG4 class, which is also associated with other risks.
Influenza is also an RNA virus, but with haemagglutinin (“HA”) and neuraminidase (“NA”) proteins on its surface, rather than the spike proteins present on coronaviruses. As with the spike protein, HA and NA proteins mutate rapidly. This forms the theory behind annual updates to influenza vaccines as manufacturers attempt to predict evolutionary changes to the HA and NA proteins.
In a recent study, the same Cleveland Clinic researchers followed over 53,000 employees through the 2024-2025 US influenza season, which lasted for 25 weeks from 1 October 2024. The preprint of their study was published at ‘Effectiveness of the Influenza Vaccine During the 2024-2025 Respiratory Viral Season’.
Cleveland Clinic employees are mandated either to receive an annual influenza vaccine or to seek an exemption on medical or religious grounds. By the end of the study, 82.1% of the study cohort had received an influenza vaccine, and 98.7% of these received an inactivated 3-valent influenza vaccine.
A proportional hazards model was used to calculate the relative risk between vaccinated and unvaccinated people, adjusting for age, sex, clinical nursing job and location to minimise potential bias. Participants were only counted as vaccinated seven days after receiving a single dose of influenza vaccine.
The outcome for influenza-vaccinated employees by the end of the study was a statistically significant 26.9% increased risk of testing positive for influenza compared with employees who did not receive the seasonal vaccine.
Hellbound and Down 