Dataset Information

Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID-19.

ABSTRACT:

Aims

Several reports indicate that diabetes determines an increased mortality risk in patients with coronavirus disease 19 (COVID-19) and a good glycaemic control appears to be associated with more favourable outcomes. Evidence also supports that COVID-19 pneumonia only accounts for a part of COVID-19 related deaths. This disease is indeed characterised by abnormal inflammatory response and vascular dysfunction, leading to the involvement and failure of different systems, including severe acute respiratory distress syndrome, coagulopathy, myocardial damage and renal failure. Inflammation and vascular dysfunction are also well-known features of hyperglycemia and diabetes, making up the ground for a detrimental synergistic combination that could explain the increased mortality observed in hyperglycaemic patients.

Materials and methods

In this work, we conduct a narrative review on this intriguing connection. Together with this, we also present the clinical characteristics, outcomes, laboratory and histopathological findings related to this topic of a cohort of nearly 1000 subjects with COVID-19 admitted to a third-level Hospital in Milan.

Results

We found an increased mortality in subjects with COVID-19 and diabetes, together with an altered inflammatory profile.

Conclusions

This may support the hypothesis that diabetes and COVID-19 meet at the crossroads of inflammation and vascular dysfunction. (ClinicalTrials.gov NCT04463849 and NCT04382794).

SUBMITTER: Bolla AM

PROVIDER: S-EPMC9349661 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID-19.

Bolla Andrea Mario AM Loretelli Cristian C Montefusco Laura L Finzi Giovanna G Abdi Reza R Ben Nasr Moufida M Lunati Maria Elena ME Pastore Ida I Bonventre Joseph V JV Nebuloni Manuela M Rusconi Stefano S Santus Pierachille P Zuccotti Gianvincenzo G Galli Massimo M D'Addio Francesca F Fiorina Paolo P

Diabetes/metabolism research and reviews 20220722 7

<h4>Aims</h4>Several reports indicate that diabetes determines an increased mortality risk in patients with coronavirus disease 19 (COVID-19) and a good glycaemic control appears to be associated with more favourable outcomes. Evidence also supports that COVID-19 pneumonia only accounts for a part of COVID-19 related deaths. This disease is indeed characterised by abnormal inflammatory response and vascular dysfunction, leading to the involvement and failure of different systems, including sever ...[more]

PMID: 35830597

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Project description:A wide range of cardiac symptoms have been observed in COVID-19 patients, often significantly influencing the clinical outcome. While the pathophysiology of pulmonary COVID-19 manifestation has been substantially unraveled, the underlying pathomechanisms of cardiac involvement in COVID-19 are largely unknown. In this multicentre study, we performed a comprehensive analysis of heart samples from 24 autopsies with confirmed SARS-CoV-2 infection and compared them to samples of age-matched Influenza H1N1 A (n = 16), lymphocytic non-influenza myocarditis cases (n = 8), and non-inflamed heart tissue (n = 9). We employed conventional histopathology, multiplexed immunohistochemistry (MPX), microvascular corrosion casting, scanning electron microscopy, X-ray phase-contrast tomography using synchrotron radiation, and direct multiplexed measurements of gene expression, to assess morphological and molecular changes holistically. Based on histopathology, none of the COVID-19 samples fulfilled the established diagnostic criteria of viral myocarditis. However, quantification via MPX showed a significant increase in perivascular CD11b/TIE2 + -macrophages in COVID-19 over time, which was not observed in influenza or non-SARS-CoV-2 viral myocarditis patients. Ultrastructurally, a significant increase in intussusceptive angiogenesis as well as multifocal thrombi, inapparent in conventional morphological analysis, could be demonstrated. In line with this, on a molecular level, COVID-19 hearts displayed a distinct expression pattern of genes primarily coding for factors involved in angiogenesis and epithelial-mesenchymal transition (EMT), changes not seen in any of the other patient groups. We conclude that cardiac involvement in COVID-19 is an angiocentric macrophage-driven inflammatory process, distinct from classical anti-viral inflammatory responses, and substantially underappreciated by conventional histopathologic analysis. For the first time, we have observed intussusceptive angiogenesis in cardiac tissue, which we previously identified as the linchpin of vascular remodeling in COVID-19 pneumonia, as a pathognomic sign in affected hearts. Moreover, we identified CD11b + /TIE2 + macrophages as the drivers of intussusceptive angiogenesis and set forward a putative model for the molecular regulation of vascular alterations.

Dataset Information

Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID-19.

Aims

Materials and methods

Results

Conclusions

Publications

Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID-19.

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