mRNA COVID-19 vaccines are less effective against Omicron infections than other variants. A study published December 1 in the open-access journal PLOS Medicine by Margaret L. Lind at the Yale School of Public Health and colleagues suggests that the additional protection offered by the original booster shot may be reduced among people with a previous COVID-19 infection.
Evidence indicates that primary (two-dose) and original booster mRNA (third dose) vaccination significantly reduces the risk of Omicron-related infection and severe outcomes in the general population. However, the benefit of mRNA COVID-19 vaccination in people who have previously experienced infection remains unclear.
In order to estimate the effectiveness of mRNA vaccination against Omicron infection among people with a prior documented infection, the researchers conducted a test-negative case control study using health records obtained through a COVID-19 study of vaccine-eligible people older than five who had at least one SARS-CoV-2 test in the Yale New Haven Health system electronic medical records.
The study group included 11,307 people who tested positive for SARS-CoV-2 between November 1, 2021 and April 30, 2022 as well as 130,041 control cases who tested negative in the same time period. The researchers then estimated vaccine effectiveness against infection and additionally whether an original booster dose was associated with increased protection beyond primary vaccination. This was achieved by comparing the odds of infection between boosted and booster-eligible people with and without a documented prior infection.
The researchers found that primary vaccination provided protection against Omicron infection among people with and without a documented prior infection. While original booster vaccination was associated with additional protection against Omicron infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection.
“This study is an example of how leveraging rich data from a health care system such as Yale New Haven Health, can address key questions during the pandemic,” said Dr. Wade Schulz, an assistant professor of laboratory medicine and a computational health researcher at the Yale School of Medicine. Schulz is a co-author on the study.
The researchers emphasize that while the original booster may not provide additional benefits in preventing Omicron infection in some people, it still offers the best protection against severe illness and hospitalization, according to previous studies.
This study was limited to Omicron infections and should be considered alongside other existing and future studies examining the relative benefits of booster doses against severe COVID-19 disease among people with and without prior infections. Additionally, this analysis was conducted prior to the distribution of the bivalent COVID-19 booster and the findings are limited to associations between the original vaccines and Omicron infection.
“In this retrospective study, we found that primary mRNA vaccination provides moderate protection against Omicron (BA.1 lineage) infection regardless of prior infection history,” said Lind, a postdoctoral associate at the Yale School of Medicine and the study’s lead author. “However, the relative benefits of an original booster dose against Omicron infection may be affected by a person’s history of prior SARS-CoV-2 infection.”
Yale School of Public Health epidemiologist Dr. Albert Ko, also a co-author, said the study findings emphasize the need for better vaccines to block SARS-CoV-2 infection.
“This study underscores the need for improved vaccines that prevent infections and reduce the possibility that new variants will emerge,” said Ko, Yale’s Raj and Indra Nooyi Professor of Public Health, and a professor of epidemiology (microbial diseases) and of medicine (infectious diseases). “Although current vaccines provide protection against severe disease, their effectiveness against infection was low regardless of whether people had or did not have a prior infection.”
Content from a PLOS Medicine news release was used in this article with permission.