A Silent Outbreak of Hepatitis E Virus (HEV) Infection or False-Positive Reaction of Anti-HEV IgM after COVID-19 Vaccination? Epidemiological Investigation of an Outbreak in a Korean Factory Complex in 2022.

Abstract

To investigate a reported outbreak of presumed hepatitis E virus (HEV) infection in a Korean food manufacturing facility and to explore the association between anti-HEV immunoglobulin M (IgM) positivity and coronavirus disease 2019 (COVID-19) infection or vaccination. Twenty-four cases of anti-HEV IgM positivity were reported among 646 workers at the facility in 2022. An epidemiological investigation was conducted, comprising HEV-RNA testing of blood and environmental samples, analysis of group meal records, and an association between anti-HEV IgM positivity and confirmed COVID-19 infection or vaccination. All 24 patients were asymptomatic, with cases spread sporadically across the facility. HEV RNA was not detected in the serum or environmental samples. Four out of 340 meals (1.2%) showed a significantly higher proportion of anti-HEV positivity in each meal intake group than in the non-intake group on certain days. Although the cumulative rate of COVID-19 infection showed no difference, the anti-HEV IgM positive group showed significantly higher proportions of >2 doses of COVID-19 vaccination (83.3% vs 48.7%, p=0.021), vaccination within 90 days (45.8% vs 19.7%, p=0.008), and having the Moderna vaccine administered as the last vaccine (75.0% vs 14.5%, p<0.001) than those of the anti-HEV negative group. In four multivariable models, three or more COVID-19 vaccinations and the Moderna vaccine as the last vaccine were consistently associated with anti-HEV IgM positivity, while the specific day group meal intake was also a significant factor. This epidemiological investigation showed that anti-HEV IgM positivity may occur as a false-positive result related to COVID-vaccination over three times and use of the Moderna vaccine, although a portion of true HEV infection may not be excluded.