A scientific detective story connecting asymptomatic hepatitis E cases to COVID-19 vaccination in a Korean factory
In the spring of 2022, a routine health check at a Korean food manufacturing factory revealed something startling—several employees had tested positive for hepatitis E virus (HEV) infection. Yet, none showed the typical symptoms of the disease: no fever, no fatigue, no jaundice. This was the beginning of a scientific detective story that would eventually connect these surprising findings to an unexpected source—COVID-19 vaccination 2 6 .
Tested positive for HEV IgM antibodies
No typical hepatitis symptoms observed
Strong correlation with COVID-19 vaccination
Hepatitis E virus is a significant global health concern, responsible for approximately 20 million infections worldwide each year, leading to an estimated 44,000 deaths annually 1 6 . Traditionally associated with developing countries and contaminated water supplies, HEV has increasingly appeared in developed nations through foodborne transmission, typically from undercooked meat products, especially pork and wild game 5 .
When the first cases appeared, Korean public health authorities launched a comprehensive investigation at the food manufacturing facility. The scope was extensive—646 employees were tested for HEV IgM antibodies, representing virtually the entire workforce 6 .
| Characteristic | Details | Significance |
|---|---|---|
| Number of Cases | 24 out of 646 employees (3.7%) | Higher than expected background rate |
| Symptom Profile | All asymptomatic | Unusual for typical HEV outbreak |
| Demographics | Median age 42.5 years, 76.5% male | No specific age or gender clustering |
| Workplace Distribution | Spread sporadically across facility | Not concentrated in specific departments |
Spring 2022 - Routine health checks reveal HEV IgM positive employees
All 646 employees tested for HEV IgM antibodies
Water, surfaces, food products tested using qRT-PCR - all negative for HEV RNA 5 6
Cafeteria meal records analyzed - inconsistent with point-source outbreak 6
2-3 months later - some developed HEV IgG but no HEV RNA detected 5
As the environmental investigation yielded puzzling results, researchers turned their attention to a novel hypothesis: could COVID-19 vaccination be influencing the HEV test results? This line of investigation proved to be the most revealing aspect of the entire study 6 .
Multiple regression models confirmed that both multiple COVID-19 vaccinations and receipt of the Moderna vaccine remained significantly associated with HEV IgM positivity, suggesting a potential effect on the immune system that might influence diagnostic test results 6 .
The investigation of this unusual outbreak relied on several sophisticated laboratory techniques and reagents. Here are the key tools that enabled researchers to unravel this medical mystery:
| Tool/Method | Function | Role in this Investigation |
|---|---|---|
| abia HEV IgM ELISA Kit | Detects IgM antibodies against HEV | Initial screening of employees for HEV infection |
| PowerChek HEV Virus qRT-PCR Kit | Amplifies and detects HEV RNA genetic material | Testing blood and environmental samples for actual virus |
| TaqMan Analysis | Quantitative method to measure specific DNA sequences | Detecting and quantifying HEV RNA in environmental samples |
| ORF 2/3 Region Primers/Probes | Target specific regions of the HEV genome | Ensuring specific detection of HEV rather than other viruses |
These tools collectively enabled researchers to distinguish between actual infection (which would show both IgM antibodies and viral RNA) and apparent seropositivity (IgM antibodies without detectable virus), which proved crucial to understanding the unusual nature of this outbreak 6 .
With conflicting evidence from different investigative approaches, researchers faced the challenging task of interpreting these findings. The central question remained: were these results evidence of a genuine HEV outbreak, or were they reflecting something more complex?
The investigation ultimately concluded that while some true HEV infections couldn't be definitively excluded, the evidence strongly suggested that COVID-19 vaccination—particularly multiple doses and the Moderna vaccine—might induce a cross-reactive immune response that could be detected as positive on HEV IgM tests without actual infection 6 .
This unusual outbreak investigation carries significant implications for public health practices, particularly in the post-pandemic era:
The findings highlight potential challenges in interpreting traditional diagnostic tests in recently vaccinated populations. As the study authors noted, "anti-HEV IgM tests show a low concordance rate among the different test kits and false-positive results" in various conditions 6 . The COVID-19 vaccination may represent another factor that can influence these results.
The investigation underscores the critical importance of confirming positive antibody tests with molecular methods like PCR when possible. Had researchers relied solely on IgM testing, they might have incorrectly concluded a genuine HEV outbreak occurred. The combination of serological and molecular testing provided a more complete picture 6 .
This case suggests that future outbreak investigations may need to consider vaccination history as a potential factor in unexpected serological findings. This is particularly relevant as new vaccine platforms and technologies continue to emerge.
While this investigation occurred in Korea, the findings have global implications. With billions of people worldwide receiving COVID-19 vaccinations, similar phenomena might occur in different populations and with different diagnostic tests. Recognizing this potential can prevent misinterpretations and unnecessary public health interventions.
The story of the Korean factory outbreak represents more than just an isolated incident—it illustrates the complex interplay between emerging infectious diseases, diagnostic technologies, and massive global vaccination efforts. While the precise biological mechanism behind the association between COVID-19 vaccination and HEV IgM positivity remains to be fully elucidated, the epidemiological evidence strongly suggests a relationship worthy of further investigation 2 6 .