Table 1.

Overview of examined samples, patients, and research question

Subject	Sample type	Viral load (IU/mL)	Description	Research question / challenge	Background described in
1	CSF	6.15E+03	patient had encephalitis of unknown origin with atypical symptoms, HEV infection retrospectively identified through HTS	Typing, Virus variant/mutation causative for CNS symptomatic?	this study (study previously mentioned in [39])
2	FFPE sample from a liver biopsy	~1E+04*	liver biopsy obtained after rejection of transplant, stored as FFPE mounted on a microscope slide for >5 years at room temperature	Typing, Sequencing of HEV from a degraded FFPE sample stored under improper conditions	Hillebrandt et al., unpublished
3	serum	4.18E+04	HEV detected in an Irish blood donation, subtyping through fragment sequencing failed	Typing, New variant/genotype that caused subtyping to fail?	[30]
4	serum	6,96E+03	HEV genotype 7 from a camel sampled in 1983	Obtaining a genome of a serum sample as old as ~ 40 years with repeated freeze-thaw cycles	[40]
5a	serum	2.46E+06	chronic HEV infection in a n immunocompromised patient with fatal outcome	Compartment-specific subpopulation that contributed to patients’ clinical outcome? (Subpopulation with) ribavirin resistance mutations? Intra-host viral evolution? High background of host nucleic acids.	unpublished/this study
5b	duodenum	1.74E+06
5c	liver	1.86E+06
5d	medulla oblongata	5.62E+06

^*Due to the FFPE fixation this concentration is an estimate.