How could we forget immunometabolism in SARS-CoV2 infection or COVID-19?

Kumar, Vijay

doi:10.1080/08830185.2020.1840567

Cited by 34 publications

(53 citation statements)

References 267 publications

(401 reference statements)

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“…In such metabolic reprogramming, increased expression of hypoxia-1 alpha-inducing factor (HIF-1α) protein contributes to the previously mentioned decreased activity of pyruvate dehydrogenase by inhibiting the pyruvate dehydrogenase complex (Andrejeva and Rathmell, 2017;Kumar, 2020). This explains the inhibition of oxidative phosphorylation, giving rise to aerobic glycolysis or hyperglycolysis (Figure 1) (Bergsneider et al, 1997;Andrejeva and Rathmell, 2017;Kumar, 2020).…”

Section: The Glycolytic Pathwaymentioning

confidence: 99%

“…In the situations involving metabolic reprogramming described above, there is thus an enzymatic redefinition that involves decreased pyruvate dehydrogenase activity and increased lactate dehydrogenase (LDH) levels (Figure 1) (Seheult et al, 2017). In such metabolic reprogramming, increased expression of hypoxia-1 alpha-inducing factor (HIF-1α) protein contributes to the previously mentioned decreased activity of pyruvate dehydrogenase by inhibiting the pyruvate dehydrogenase complex (Andrejeva and Rathmell, 2017;Kumar, 2020). This explains the inhibition of oxidative phosphorylation, giving rise to aerobic glycolysis or hyperglycolysis (Figure 1) (Bergsneider et al, 1997;Andrejeva and Rathmell, 2017;Kumar, 2020).…”

Section: The Glycolytic Pathwaymentioning

confidence: 99%

“…The second component involves a decrease, or, at least a significant delay, in production of type 1 Interferons (IFN) by SARS-CoV-2-infected cells, namely respiratory epithelial cells and macrophages (Jafarzadeh et al, 2020;Kumar, 2020;Merad and Martin, 2020). Such a deficiency in type 1 IFN is crucial to progression of COVID-19 disease since the anti-viral role of this type of interferons is essential to dealing with the infection (Jafarzadeh et al, 2020;Paces et al, 2020;Gustine and Jones, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Changes in Glycolytic Pathway in SARS-COV 2 Infection and Their Importance in Understanding the Severity of COVID-19

et al. 2021

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COVID-19 is an infectious disease caused by Coronavirus 2 (SARS-CoV-2) that may lead to a severe acute respiratory syndrome. Such syndrome is thought to be related, at least in part, to a dysregulation of the immune system which involves three main components: hyperactivity of the innate immune system; decreased production of type 1 Interferons (IFN) by SARS-CoV-2-infected cells, namely respiratory epithelial cells and macrophages; and decreased numbers of both CD4+ and particularly CD8+ T cells. Herein, we describe how excessive activation of the innate immune system and the need for viral replication in several cells of the infected organism promote significant alterations in cells’ energy metabolism (glucose metabolism), which may underlie the poor prognosis of the disease in severe situations. When activated, cells of the innate immune system reprogram their metabolism, and increase glucose uptake to ensure secretion of pro-inflammatory cytokines. Changes in glucose metabolism are also observed in pulmonary epithelial cells, contributing to dysregulation of cytokine synthesis and inflammation of the pulmonary epithelium. Controlling hyperglycolysis in critically ill patients may help to reduce the exaggerated production of pro-inflammatory cytokines and optimise the actions of the adaptive immune system. In this review, we suggest that the administration of non-toxic concentrations of 2-deoxy-D-glucose, the use of GLUT 1 inhibitors, of antioxidants such as vitamin C in high doses, as well as the administration of N-acetylcysteine in high doses, may be useful complementary therapeutic strategies for these patients, as suggested by some clinical trials and/ or reports. Overall, understanding changes in the glycolytic pathway associated with COVID-19 infection can help to find new forms of treatment for this disease.

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Section: The Glycolytic Pathwaymentioning

confidence: 99%

Section: The Glycolytic Pathwaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes in Glycolytic Pathway in SARS-COV 2 Infection and Their Importance in Understanding the Severity of COVID-19

et al. 2021

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“…Interestingly, displacement of HK2 from mitochondria of dendritic cells was proposed to be involved in their death during SARS-CoV2 infection [ 47 ].…”

Section: Hk2 Regulation: Where How and Whymentioning

confidence: 99%

Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

Ciscato

Ferrone

Masgras

et al. 2021

IJMS

106

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Hexokinases are a family of ubiquitous exose-phosphorylating enzymes that prime glucose for intracellular utilization. Hexokinase 2 (HK2) is the most active isozyme of the family, mainly expressed in insulin-sensitive tissues. HK2 induction in most neoplastic cells contributes to their metabolic rewiring towards aerobic glycolysis, and its genetic ablation inhibits malignant growth in mouse models. HK2 can dock to mitochondria, where it performs additional functions in autophagy regulation and cell death inhibition that are independent of its enzymatic activity. The recent definition of HK2 localization to contact points between mitochondria and endoplasmic reticulum called Mitochondria Associated Membranes (MAMs) has unveiled a novel HK2 role in regulating intracellular Ca2+ fluxes. Here, we propose that HK2 localization in MAMs of tumor cells is key in sustaining neoplastic progression, as it acts as an intersection node between metabolic and survival pathways. Disrupting these functions by targeting HK2 subcellular localization can constitute a promising anti-tumor strategy.

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“…Little is known about the durability and nature of the humoral immune response to SARS-CoV-2 in individuals with diabetes ( 11 , 12 ) and cases of COVID-19 recurrences have been indeed described in subjects with diabetes ( 13-17 ). More generally, whether hyperglycemia modulates the antibody response to a virus and its durability, it is still a matter of discussion ( 18 , 19 ). Decreased immunological response to the hepatitis B vaccine was consistently reported in individuals with diabetes ( 20 ), while less consistent responses were noted for varicella zoster and influenza vaccines ( 21 , 22 ).…”

mentioning

confidence: 99%

Robust Neutralizing Antibodies to SARS-CoV-2 Develop and Persist in Subjects with Diabetes and COVID-19 Pneumonia

Dispinseri

Lampasona

Secchi

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Purpose The aim of this study was to characterise the kinetics and durability of neutralizing antibody (Nab) response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of hyperglycemia. Methods Using a lentiviral-vector-based SARS-CoV-2 neutralization assay to measure Nabs, we characterised 150 patients randomly selected from a cohort of 509 patients with confirmed COVID-19 pneumonia. We analysed Nab response according to the presence of diabetes or hyperglycaemia, at the time of hospitalisation and during the post discharge follow-up, i.e., 1, 3 and 6 months outpatient visits. Results Among 150 randomly selected patients 40 (26.6%) had diabetes. Diabetes (HR 8.9, p < 0.001), glucose levels (HR 1.25 x 1.1 mmol/L, p < 0.001) and glucose variability (HR 1.17 x 0.6 mmol/L, p < 0.001) were independently associated with an increased risk of mortality. The neutralizing activity of SARS-CoV-2 antibodies in patients with diabetes was superimposable, as for kinetics and extent, to that of patients without diabetes. It was similar across glucose levels and correlated with the humoral response against the SARS-CoV-2 spike protein. Positivity for Nabs at the time of hospital admission conferred protection on mortality, both in the presence (HR 0.28, p=0.046) or absence of diabetes (HR 0.26, p=0.030). The longevity of the Nab response was not affected by diabetes. Conclusions Diabetes and hyperglycaemia do not affect the kinetics and durability of the neutralizing antibody response to SARS-CoV-2. These findings provide the rational to include patients with diabetes in the early phase of the vaccination campaign against SARS-CoV-2.

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How could we forget immunometabolism in SARS-CoV2 infection or COVID-19?

Cited by 34 publications

References 267 publications

Changes in Glycolytic Pathway in SARS-COV 2 Infection and Their Importance in Understanding the Severity of COVID-19

Changes in Glycolytic Pathway in SARS-COV 2 Infection and Their Importance in Understanding the Severity of COVID-19

Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

Robust Neutralizing Antibodies to SARS-CoV-2 Develop and Persist in Subjects with Diabetes and COVID-19 Pneumonia

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