ABSTRACT
AIMS: COVID-19 patients with type 2 diabetes mellitus (T2DM) show both poorer clinical outcomes and have an increased risk of death. SARS-CoV-2 virus infection requires simultaneous expression of the SARS-CoV-2 cell entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2) in the same cell. The aim of the study was to explore the underlying mechanisms of a COVID-19 infection in patients with T2DM. METHODS: The distribution and expression of AEC2 and TMPRSS2 in different pancreatic cell types in clinical samples of T2DM patients and diabetic mouse models were analysed by single-cell sequencing, bioinformatics analysis and basic experiments. RESULTS: The results showed that ACE2 and TMPRSS2 are expressed in the ducts of the human pancreas. These findings suggest that SARS-CoV-2 can infect ductal cells in vivo through ACE2 and TMPRSS2. T2DM can promote the co-expression of ACE2 and TMPRSS2 in exocrine ducts, including in the human pancreas. We hypothesize that ACE2 expression levels are associated with increased numbers of lymphocytes in vivo. CONCLUSIONS: Increased blood glucose levels are associated with increased ACE2 expression and an increased number of lymphocytes. At the same time, lymphocytes can promote ACE2 expression.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the global coronavirus disease 2019 (COVID-19) pandemic. Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression. In the present study, we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-CoV-2. Results revealed that SARS-CoV-2 replication was delayed in hypertensive mouse lungs. In contrast, SARS-CoV-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-CoV-2-infected normotensive mice. Furthermore, antihypertensive treatment alleviated lung inflammation induced by SARS-CoV-2 replication (interleukin (IL)-1ß up-regulation and increased immune cell infiltration). No differences in lung inflammation were observed between the SARS-CoV-2-infected normotensive mice and hypertensive mice. Our findings suggest that captopril treatment may alleviate COVID-19 progression but not affect viral replication.