Morphological prediction of lethal outcomes in the evaluation of lung tissue structural changes in patients on respiratory support with СOVID-19: Ukrainian experience.

The impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on lung tissue in patients on respiratory support is of significant scientific interest in predicting mortality. This study aimed to analyze post-mortem histological changes in the lung tissue of COVID-19 patients on respiratory support using vital radiology semiotics. A total of 41 autopsies were performed on patients who died of SARS-CoV-2 and had confirmed COVID-19 by polymerase chain reaction (PCR) and radiological evidence of lung tissue consolidation and ground glass opacity. The results showed that the duration of COVID-19 in patients on respiratory support was significantly associated with the development of all stages of diffuse alveolar damage, acute fibrous organizing pneumonia, pulmonary capillary congestion, fibrin thrombi, perivascular inflammation, alveolar hemorrhage, proliferating interstitial fibroblasts, and pulmonary embolism. The prediction model for lethal outcomes based on the duration of total respiratory support had a sensitivity of 68.3% and a specificity of 87.5%. In conclusion, for COVID-19 patients on long-term respiratory support with radiological signs of ground glass opacity and lung consolidation, post-mortem morphological features included various stages of diffuse alveolar lung damage, pulmonary capillary congestion, fibrin clots, and perivascular inflammation.

Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential.

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has become a serious challenge for medicine and science. Analysis of the molecular mechanisms associated with the clinical manifestations and severity of COVID-19 has identified several key points of immune dysregulation observed in SARS-CoV-2 infection. For diabetic patients, factors including higher binding affinity and virus penetration, decreased virus clearance and decreased T cell function, increased susceptibility to hyperinflammation, and cytokine storm may make these patients susceptible to a more severe course of COVID-19 disease. Metabolic changes induced by diabetes, especially hyperglycemia, can directly affect the immunometabolism of lymphocytes in part by affecting the activity of the mTOR protein kinase signaling pathway. High mTOR activity can enhance the progression of diabetes due to the activation of effector proinflammatory subpopulations of lymphocytes and, conversely, low activity promotes the differentiation of T-regulatory cells. Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK. Therefore, activation of AMPK and/or inhibition of the mTOR-mediated signaling pathway may be an important new target for drug therapy in COVID-19 cases mostly by reducing the level of pro-inflammatory signaling and cytokine storm. These suggestions have been partially confirmed by several retrospective analyzes of patients with diabetes mellitus hospitalized for severe COVID-19.