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

Abstract The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken its toll on worldwide public health infrastructure. SARS-CoV-2 is reported to exhibit wide tissue tropism, contributing to its severe pathogenicity that often culminates in multiple-organ failure. The onslaught of this disease has intensified due to the emergence of variants of concern (VOC), such as Delta and Omicron. These variants have been linked to gastrointestinal (GI) symptoms, suggesting a potential fecal-oral route of viral transmission. Here we compared the broad tissue tropism of ancestral Hong-Kong SARS-CoV-2 (SARS-CoV-2 HK) against Delta and Omicron VOCs in aa hamster model by analyzing tissue samples collected from the upper and lower respiratory system and the GI tract. We observed an overall increase in vRNA load and pro- inflammatory cytokines, especially in GI tracts of animals infected with Delta virus, indicating selective virus tropism and pathology in these tissues. However, no apparent spike in Delta viral load was observed in the large intestine and fecal matter. Overall, our research investigates the wide range of tissues that various SARS-CoV-2 strains can infect in hamsters and presents evidence supporting the increased preference of Delta VOCs for infecting the GI tract.