The United States Centers for Disease Control and Prevention (CDC) updated their guidance on coronavirus disease 2019 (COVID-19) vaccination in April 2023. All individuals above the age of six who had received at least one dose of a COVID-19 bivalent vaccine were considered to be “up-to-date” with COVID-19 vaccination. Conversely, individuals were considered to be not “up-to-date” if they had not received a single dose of a COVID-19 bivalent vaccine.
Study: Risk of Coronavirus Disease 2019 (COVID-19) among Those Up-to-Date and Not Up-to-Date on COVID-19 Vaccination. Image Credit: ONGUSHI / Shutterstock.com
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Recent research has not been able to document the efficacy of the bivalent vaccine, while the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB variants were the dominant circulating strains. Given that these viral variants remain the dominant circulating strains, it is reasonable to ask whether “up-to-date” individuals, with a vaccine of inconclusive effectiveness, are protected against COVID-19 as compared to their not “up-to-date” counterparts.
Addressing this issue, a recent study posted to the medRxiv* preprint server investigates whether not “up-to-date” individuals had a higher risk of COVID-19 than “up-to-date” individuals.
About the study
The current retrospective cohort study was conducted at the Cleveland Clinic Health System (CCHS). The COVID-19 bivalent messenger ribonucleic acid (mRNA) vaccine was first offered to employees on September 12, 2022. The start date of this study was January 23, 2023, which was when XBB lineages first became the dominant circulating strains in Ohio.
Study participants were CCHS employees in any location on September 12, 2022, and remained employed when the XBB lineages became dominant. Individuals were excluded if their age and sex data were unavailable.
The outcome variable was time to COVID-19, which was defined as a positive SARS-CoV-2 nucleic acid amplification test (NAAT). The study participants were closely monitored until May 10, 2023, which allowed for the evaluation of outcomes up to 100 days from the inception of the study.
Key findings
A total of 48,344 participants were considered, 1,445 of whom were censored because of termination of employment. Within the study cohort, 12,841 were “up-to-date” on COVID-19 vaccination by the end of the study.
Of these individuals, 11,187 received the Pfizer vaccine and 1,654 received the Moderna vaccine. A total of 1,475 employees were infected with SARS-CoV-2 during the 100-day study period.
The population was relatively young, with a mean age of 43 years. About 46% had a previous history of COVID-19 and 34% were infected by the Omicron variant. Moreover, 87% of the study cohort received at least one vaccine dose and 92% were exposed to SARS-CoV-2 by infection or vaccination.
The risk of COVID-19 was lower in the “not up-to-date” group as compared to the “up-to-date” group. On analyzing tertiles of propensity to get tested for SARS-CoV-2 infection, the not “up-to-date” group was not more likely to contract COVID-19.
The classification for risk of COVID-19 was more appropriately provided by considering prior infection status. A significantly lower risk of COVID-19 was observed in individuals who were least affected by the Omicron BQ or BA.4/BA.5 variants. However, no clear difference was noted between “up-to-date” and “not up-to-date” individuals when stratified by the most recent infection date.
One reason why being “up-to-date,” based on the CDC definition, was not associated with a lower risk of COVID-19 was that the bivalent vaccine was less effective against the XBB lineages of the Omicron variant. Another reason could be that the CDC definition ignores the protective effect of immunity acquired from prior infection.
Conclusions
The current study reports that being not “up-to-date” on vaccination was associated with a lower risk of COVID-19 than being “up-to-date.” These findings demonstrate the challenges of gauging vaccine protection when efficacy wanes over time and the method of classifying risk is only based on the receipt of a vaccine of questionable effectiveness.
The key strengths of this study include its large sample size and that it was conducted in a country that devoted significant resources to accurately tracking the progression of the pandemic. Additionally, the methodology of treating vaccination status as a time-dependent covariate enabled the determination of vaccine efficacy in real time.
The present study focused on all detected infections and did not distinguish between asymptomatic and symptomatic infections. Several asymptomatic and mildly symptomatic infections could have been accidentally ignored, which would make information on prior COVID-19 incomplete.
Furthermore, the question of whether being “up-to-date” decreased the severity of illness could not be studied due to the rarity of severe illnesses. Lastly, owing to the young study population, the effects on immunocompromised subjects could not be studied.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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