Type 1 Diabetes Mellitus in Domestic Cats Infected with SARS-CoV-2: Pancreatic Pathogenesis and Antiviral Therapeutics

In recent years, significant research has established that remdesivir and its parent nucleoside analog GS-441524 substantially improve clinical outcomes and reduce viral shedding in cats suffering from coronavirus-induced feline infectious peritonitis (FIP). Similarly, molnupiravir - another potent nucleoside analog - has gained prominence for its dual utility in treating FIP in veterinary medicine and COVID-19 in humans. In Japan, molnupiravir has been approved for clinical use since late 2021. Experimental animal models have provided insights into these mechanisms. Immunohistochemical (IHC) analysis has identified the expression of the SARS-CoV-2 nucleocapsid protein (NP) within pancreatic islet cells of humans and in infected cats, with NP expression increasing in a time-dependent manner following infection. Notably, IHC analysis also revealed NP staining within pancreatic ductal epithelial cells. Given that ductal epithelial cells serve as progenitors that differentiate into islet cells during development, this suggests a possible pathway for direct viral invasion of the endocrine islets. While the precise mode of viral entry remain to be elucidated, these findings underscore the potential for SARS-CoV-2 to directly compromise pancreatic integrity and endocrine function. Hence, antiviral drugs could counteract also the diabetogenic effect of coronaviruses in both animals and humans.