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Gene Rep . Enhanced endocytosis elevated virulence and severity of SARS-CoV-2 due to hyperglycemia in type 2 diabetic patients

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  • Gene Rep . Enhanced endocytosis elevated virulence and severity of SARS-CoV-2 due to hyperglycemia in type 2 diabetic patients


    Gene Rep


    . 2022 Jan 14;101495.
    doi: 10.1016/j.genrep.2022.101495. Online ahead of print.
    Enhanced endocytosis elevated virulence and severity of SARS-CoV-2 due to hyperglycemia in type 2 diabetic patients


    Kannan Subbaram 1 , P Shaik Syed Ali 1 , Sheeza Ali 1



    Affiliations

    Abstract

    Diabetes mellitus is a metabolic disease that causes hyperglycemia. In COVID-19 patients the severity of the disease depends on myriad factors but diabetes mellitus is the most important comorbidity. The current review was conducted to investigate the virulence of SARS-CoV-2 and disease severity of COVID-19 in type 2 diabetes mellitus patients and relevant treatment. The literature published in PubMed, Scopus, Web of Science, and Google Scholar was reviewed up to September 2021. The keywords including SARS-CoV-2, type 2 diabetes mellitus in COVID-19, hyperglycemia in COVID-19, opportunistic infections in type 2 diabetes mellitus and COVID-19 were used in different combinations. Hyperglycemic individuals over-express ACE-2 receptors in the lungs thus increasing the SARS-CoV-2 susceptibility and replication. Although dipeptidyl peptidase-4 plays an important role in glucose homeostasis, additionally it also stimulates the production of proinflammatory cytokines such as IL-6 and TNF-α creating a cytokine storm. Cytokine storm might be responsible for respiratory insufficiency in severe COVID-19 patients. Type 2 diabetes mellitus is associated with immunosuppression and the patients are prone to get many opportunistic infections. Type 2 diabetes mellitus patients with severe COVID-19 have lymphopenia. Moreover, in type 2 diabetes mellitus patients the neutrophils exhibit decreased chemotaxis, hydrogen peroxide production, and phagocytosis. Reduction in lymphocyte count and defective neutrophil capacity renders them with COVID-19 susceptible to opportunistic bacterial and fungal infections increasing the mortality rate. The opportunistic bacterial infections in COVID-19 patients were due to Staphylococcus aureus, Streptococcus pneumonia, and coagulase-negative Staphylococci, E. coli, Pseudomonas aeruginosa, and Klebsiella sp. In COVID-19 patients with type 2 diabetes mellitus, mucormycosis was found to be the most common fungal infection with a higher predilection to males. Hyperglycemia in COVID-19 patients with type 2 diabetes mellitus enhances the SARS-CoV-2 replication with an adverse outcome. A strong correlation exists between the poor prognosis of COVID-19 and type 2 diabetes mellitus. Proper glycemic control in COVID-19 patients with diabetes mellitus might lessen the severity of the disease.

    Keywords: ACE-2, Angiotensin-converting enzyme 2; ARDS, Acute respiratory distress syndrome; ATP, Adenosine tri phosphate; CLR, C-lectin type receptors; COVID-19; COVID-19, Coronavirus disease 2019; Endocytosis; GRP78, non-immune receptor glucose regulated protein 78; Hyperglycemia; IFN-1, Interferon-1; MERS, Middle East respiratory syndrome; NRP1, neuropilin-1; Opportunistic infections; SARS, Severe acute respiratory syndrome; SARS-CoV-2; SARS-CoV-2, Severe acute respiratory syndrome coronavirus-2; T2DM, Type 2 diabetes mellitus; TLR, toll-like receptors; TMPRSS2, Transmembrane Serine Protease 2; Type 2 diabetes mellitus; WHO, World Health Organization.

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