# Long-lasting IgM and declining IgG levels: a serologic 5-year follow-up study in healthy blood donors infected with hepatitis E virus

## TL;DR

This study tracks HEV antibody levels in blood donors over five years, revealing long-lasting IgM and declining IgG, with implications for understanding immunity and blood safety.

## Contribution

The study identifies long-term IgM positivity and IgG seroreversion in HEV infections, highlighting sex-based immune differences and assay variability.

## Key findings

- 7.3% of donors remained IgM-positive for HEV over five years.
- 9.1% of donors showed IgG seroreversion after five years.
- Women exhibited stronger and longer-lasting humoral immune responses to HEV.

## Abstract

Hepatitis E virus (HEV) has attracted increasing attention in transfusion medicine in recent years. Mandatory testing regimes in Europe have resulted in not only ensuring the safety of blood products, but also providing information on the spread and immunology of HEV infections. We tracked a cohort of 497 donors identified as HEV RNA-positive during blood donation. Several follow-up samples were collected and serologically analyzed for 370 of them, up to five years after the index donation. In addition to the expected increase in immunoglobulins M (IgM) and G (IgG) titers at the beginning and the decrease over the years, we observed a proportion of 7.3% with positive anti-HEV IgM (long-term IgM-positive) and 9.1% with negative anti-HEV IgG (seroreversion) in five-year follow-ups, determined by serological tests from three different manufacturers. Both phenomena have an impact on the assessment of the correlation between incidence and seroprevalence. They are dependent on the sensitivity and specificity of serologic assays used and have a sex bias, which indicates a stronger, longer-lasting humoral immune response in women. These data offer new insights into the long-term development of immunity to HEV and thus complement short-term epidemiological data on the incidence and seroprevalence that have been obtained so far.