Role of diabetes mellitus in the clinical course and outcome of SARS-CoV-2 infected patients.

PURPOSE: Our aim was to study patients with diabetes mellitus and SARS-CoV-2-infection diagnosed during the first pandemic wave in Greece. METHODS: Cases were retrieved from the national database of SARS-CoV-2 infections. RESULTS: We studied 2624 SARS-CoV-2 infected cases, including 157 with diabetes. Patients with diabetes more often had other comorbidities (68.8 vs. 24.1%; p-value < 0.001). Among patients with diabetes, 149 (94.9%) developed symptomatic disease (COVID-19) compared to 1817 patients (73.7%) without diabetes (p-value < 0.001). A total of 126 patients with diabetes and COVID-19 were hospitalized and 41 died (27.5% case-fatality rate compared to 7.5% among patients without diabetes; p-value < 0.001). Patients with diabetes more often were hospitalized, developed complications, were admitted to the intensive care unit (ICU), received invasive mechanical ventilation, and died compared to patients without diabetes (p-values < 0.001 to 0.002 for all comparisons). Multivariate logistic regression analyses revealed that diabetes, having other comorbidities, and older age were significantly associated with higher risk for hospitalization, ICU admission, invasive mechanical ventilation, and death, and that obesity was significantly associated with higher risk for hospitalization, ICU admission, and mechanical intubation, while female gender protected against these outcomes. CONCLUSION: COVID-19 is associated with increased rates of serious morbidity and adverse outcome in patients with diabetes and represents a severe illness for them.

Induction of innate immune responses by KPC-producing Klebsiella pneumoniae of the pandemic sequence type 258-clade I.

Klebsiella pneumoniae -carbapenemase-producing K. pneumoniae (KPC) sequence-type 258 (ST258) has emerged as an important human pathogen throughout the world. Although lacking known virulence factors, it is associated with significant morbidity and high mortality rates. The pathogenicity of KPC K. pneumoniae ST258 strains has not been fully elucidated yet. We sought to investigate the interactions of the KPC K. pneumoniae ST258-clade I with different components of innate immunity. Human serum was used to evaluate the serum bactericidal activity and the J774A.1 murine (BALB/c mice) macrophage cell-line was used to examine phagocytosis, mRNA expression and production of the pro-inflammatory cytokines IL-1ß, TNF-α and IL-6. L-78, a KPC-producing K. pneumoniae ST258-clade I strain was used as representative of the strains circulating in Greek hospitals. K. pneumoniae ATCC 43816, a virulent K2 strain, was used for comparison. Strain L-78 was susceptible to human serum and rapidly phagocytosed by J774A.1 cells, in contrast to the virulent K2 strain, which was serum-resistant and slowly phagocytosed. Stimulation of the J774A.1 cells with the L-78 strain induced production of IL-1ß at concentration levels significantly higher compared to K2, whereas production of TNF-α and IL-6 levels were comparable by the two strains. L-78 was able to induce IL-1ß mRNA and NLRP3 mRNA expression. Our findings indicate that K. pneumoniae ST258-clade I is serum sensitive, rapidly phagocytosed and is capable of eliciting adequate innate immune response in terms of production of pro-inflammatory cytokines.