Are High Antibody Levels Enough to Prevent Omicron Infection?

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There was a lower risk of Omicron infection for each 10-fold increase in preinfection IgG, and for each 2-fold increase in neutralizing antibody titers.

There was a lower risk of Omicron infection for each 10-fold increase in preinfection IgG, and for each 2-fold increase in neutralizing antibody titers.

Image courtesy of Adobe Stock: Studio-FI

High levels of antibodies, generated by either COVID-19 vaccination or a prior infection, were proven to reduce the risk of infection with the Wuhan wild-type, Alpha, and Delta variants. However, there is a need to determine whether this applies to the Omicron variant, which is associated with high rates of breakthrough infections.

One study, recently published in JAMA Network Open, sought to determine whether high antibody levels in individuals who received at least 3 doses of a messenger RNA (mRNA) COVID-19 vaccine protect against Omicron infection and disease.

The prospective cohort study utilized serial real time-polymerase chain reaction (RT-PCR) and serological data from January and May 2022, assessing the correlation between preinfection immunoglobin G (IgG) and neutralizing antibody titers with Omicron variant infection, symptomatic disease, and infectivity.

Included participants were health care workers who had received 3 or 4 doses of an mRNA COVID-19 vaccine. The participants were split into 3 different cohorts for 3 different analyses: 2310 patients in the protection from infectivity analysis (4689 exposure events; average age 50 years; 76.6% female), 667 patients in the symptomatic disease analysis (average age 46.28 years; 75.8% female), and 532 patients in the infectivity analysis (average age average 48 years; 75.8% female).

Investigators analyzed the data from May-August 2022. Multivariable analysis, accounting for age, sex, receipt of a fourth vaccine dose, time from last vaccination, and calendar time, estimated that higher IgG and neutralizing antibody titers were associated with a reduced probability of infection.

The investigators found a 30% lower risk of infection for each 10-fold increase in preinfection IgG, and an 11% reduced infection risk for each 2-fold increase in neutralizing antibody titers. Infectivity, however, did not significantly decrease as IgG or neutralizing antibody titers increased.

A high humoral response, regardless of the number of booster doses of time since vaccination, reduced the risk of Omicron infection and symptomatic disease. This indicates serological markers could be used to assess the risk of infection at both the individual and population level.

The investigators argued these findings can help inform the necessity and timing of booster vaccinations, even at a time of heightened Omicron infectivity.

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Paul Tambyah, MD, president of ISID
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