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.

Background/aims: 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.
Methods: 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.
Results: 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.
Conclusions: 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.