The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide. It is transmitted mainly by direct contact with patients who have been infected or by ingesting contaminated water or food. The virus is endemic in low-income countries where sanitary and sociodemographic conditions are poor. Paradoxically, improving sanitary conditions in these countries, which reduces the incidence of HAV infections, can lead to more severe disease in susceptible adults. The populations of developed countries are highly susceptible to HAV, and large outbreaks can occur when the virus is spread by globalization and by increased travel and movement of foodstuffs. Most of these outbreaks occur among high-risk groups: travellers, men who have sex with men, people who use substances, and people facing homelessness. Hepatitis A infections can be prevented by vaccination; safe and effective vaccines have been available for decades. Several countries have successfully introduced universal mass vaccination for children, but high-risk groups in high-income countries remain insufficiently protected. The development of HAV antivirals may be important to control HAV outbreaks in developed countries where a universal vaccination programme is not recommended.

Objective: Hepatitis E virus (HEV), one of the most common agent of acute hepatitis worldwide, is mainly transmitted enterically, via contaminated water for HEV genotypes 1 (HEV1) and HEV2, or by eating raw or undercooked infected meat for HEV genotype 3 (HEV3) and HEV4. However, little is known about how the ingested HEV reaches the liver or its ability to replicate in intestinal cells. Design: We developed human primary cultures of small intestine epithelial cells and intestinal explants obtained from small bowel resections. The epithelial cells were also polarised on transwells. Cells were infected with Kernow-p6 strain or clinically derived virions. Results: Primary intestinal cells supported the growth of Kernow-p6 strain and HEV1 and HEV3 clinically derived virions. Polarised enterocytes infected with HEV1 and HEV3 strains released HEV particles vectorially: mostly into the apical compartment with a little basally. Iodixanol density gradient centrifugation of enterocyte-derived HEV virions gave bands at a density of 1.06–1.08 g/cm³, corresponding to that of quasi-enveloped HEV particles. Ribavirin therapy inhibited HEV excretion from the basal surface but not from the apical side of infected human enterocytes. HEV virions also infected intestinal tissue explants. Lastly, HEV RNA and antigen were detected in the intestinal crypts of a chronically infected patient. Conclusion: HEV can replicate in intestinal cells and reaches the liver as quasi-enveloped virions.

The emergence of the SARS-CoV-2 variants of concern has greatly influenced the immune correlates of protection, and there are little data about the antibody threshold concentrations to protect against infection with SARS-CoV-2 Omicron BA.1 or BA.2. We analyzed the antibody responses of 259 vaccinated healthcare workers, some of whom had been previously infected by SARS-CoV-2. The median follow-up was 179 days (IQR: 171–182) after blood collection. We detected 88 SARS-CoV-2 Omicron infections during the follow-up period, 55 (62.5%) with SARS-CoV-2 BA.1, and 33 (37.5%) with SARS-CoV-2 BA.2. A neutralizing antibody titer below 8 provided no protection against a BA.1 infection, a titer of 16 or 32 gave 73.2% protection, and a titer of 64 or 128 provided 78.4% protection. Conversely, the BA.2 infection rate did not vary as a function of anti-BA.2 neutralizing antibody titers. Binding antibody concentrations below 6000 BAU/mL provided no protection against Omicron BA.1 infection, 6000–20,000 BAU/mL provided 55.6% protection, and 20,000 or more provided 87.7% protection. There was no difference in BA.2 infection depending on the binding antibody concentration. Further studies are needed to investigate the relationship between antibody concentrations and infection with the Omicron BA.4/5 variants that are becoming predominant worldwide.