The kinetics of asymptomatic hepatitis E virus infections in healthy individuals

Transfusion-transmitted hepatitis E virus (HEV) infection has attracted increasing attention as a cause of complications in immunocompromised patients and organ donation recipients, while infection in apparently healthy people, such as blood donors, is usually asymptomatic. Although testing of blood products for HEV is mandatory in Germany since 2020, little is known about the course of asymptomatic infections due to the immediate restriction of donors.

Samples from blood donations collected before initiation of mandatory testing were screened retrospectively for HEV RNA. Donations were made with few days distance, resulting in dense data on viral load progression. Screening involved pooling 96 samples for HEV RNA, followed by RNA extraction and polymerase chain reaction for nucleic acid detection. Viral load was quantified using internal kit standards, allowing calculation of doubling time in the first half of infection and half-life in the second half using the formula n=log(2)*log(Nt/N0). Seroconversion in HEV RNA-positive blood donors was traced by evaluating HEV IgM and IgG titers using HEV ELISA Kits.

Viremia was analyzed in 32 HEV RNA-positive individuals with a median of four days between donations. A typical median infection proceeded as follows: detectable viremia lasted for 36 days (IQR 19 – 49 days) with a maximum viral load of 2.0 ×104 IU/ml (IQR 2.0×103 – 1.5×105 IU/ml) at day 22 (IQR 10 – 27 days). A weak correlation was observed between maximum viral load and duration of infection (r = 0.5642, p = 0.0018). The average doubling time was 2.4 days (IQR 1.7 – 3.7 days; n=21), the half-life 1.6 days (IQR 0.8 – 2.2 days; n=14). HEV IgM and IgG started to rise around day 32 to 33 (IQR 24 – 40 days) and peaked on day 36 (IQR 28 – 54 days) and 53 (IQR 32 – 72 days). While HEV IgG titers were stable, IgM titers became undetectable in 40 % of the cases on median at day 85 (IQR 59 – 108 days).

Our data provide insight into the kinetics of asymptomatic HEV infections. While key characteristics such as humoral immune response, maximum and duration of viremia confirm previous studies, doubling time and half-life were additionally determined allowing a baseline evaluation of self-limiting HEV infection. By taking secondary factors (e.g. age or immune status) into account, we might determine risk factors influencing the kinetics of the infection in future studies.

Funding statement: D.T. was supported by the German Federal Ministry of Education and Research (BMBF, project: VirBio, Grant number: 01KI2106). E.S. and T.V. were supported by the German Federal Ministry of Education and Research (BMBF, project HepEDiaSeq — FKZ 01EK2106A).