SARS-CoV-2 variants of concern exhibit differential gastro-intestinal tropism and pathogenesis in the Syrian golden hamster model.

Abstract

Severe Acute Respiratory Syndrome Virus-2 (SARS-CoV-2) is a respiratory virus that uses angiotensin-converting enzyme 2 (ACE2) protein as an entry receptor. Thus, ACE2 expression levels in different tissues should dictate viral tropism. Notably, human ACE2 mRNA and protein levels are most abundant in the gastrointestinal tract, a pattern mirrored in Syrian golden hamsters. This prompted us to investigate the gastrointestinal tropism of SARS-CoV-2 variants of concern, including the Wuhan-like Hong Kong strain, highly pathogenic Delta, and highly transmissible but mildly pathogenic Omicron variants in hamsters. Delta was the most pathogenic in the respiratory and gastrointestinal tracts, followed by ancestral Wuhan-like and Omicron strains. In the gastrointestinal tract, viral RNA load was significant in the proximal organs such as the oesophagus and stomach, highest in the SI, and minimal to undetectable in the colon. Additionally, all three variants reduced fecal microbial diversity, with the Delta causing the highest decrease in observed features and phylogenetic diversity. Our findings highlight Deltas stronger preference for the gastrointestinal tract, suggesting a link between high virulence and gastrointestinal tropism of SARS-CoV-2 variants of concern.