The potential use of lactate blockers for the prevention of COVID-19 worst outcome, insights from exercise immunology

AbdelMassih, Antoine; Menshawey, Rahma; Hozaien, Rafeef; Kamel, Aya; Mishriky, Fady; Husseiny, Reem; Hanoura, Aia Mohamed; Yacoub, Elaria; AlShehry, Nada; Menshawey, Esraa; El-Husseiny, Nadine; Yasser, Reem; Arsanyous, Mariem; Nathan, Lauren; Seyam, Mahmoud; Massoud, Doaa; Ali, Nada; Kassim, Assem; AmanAllah, Mostafa; El-Sayed, Rokaya; Sheashaa, Hesham; Husseiny, Yousef; Hassan, Nourhan; Badr, Kirollos; Elkhateb, Amr; Fouad, Verina; Elfishawy, Mayada; Medhat, Omar; Mustafa, Mai; Khalil, Noha M.; Elsayed, Rawan; Nada, Youssef; Elshawarbi, Passant; Abdelmoneim, Noha; Gamal, Nada; Messiha, Mariam; Ghazy, Marihan; Abdelfatah, Emmy; Nasry, Febronia; Gayed, Ramy; Eesa, Marian; Luis, Merna; Eskandar, Estfana; Yacoub, Shenoda; Saud, Alaa; Rajab, Maram; Abdelaziz, Mariam; Elgamal, Nadine; Jaber, Hutaf; Tayssir, Sara; Michael, Mark; Sabry, Ahmed; Shehata, Joseph; Abdelaziz, Rania; Rateb, Sherry; El‐Maghraby, A. A.; Mahjoub, Yara; Amr, Alaa; Mabrouk, Amin; Kelada, Peter; Ragab, Shahd; Eltaher, Basant; Galal, Rahma Hassan; Aly, Omnya Mahmoud; Aly, Taquwa; AbdelHaleem, Rana; ElShaarawy, Areeg; Mohamed, Omnia

doi:10.1016/j.mehy.2021.110520

Cited by 7 publications

(8 citation statements)

References 39 publications

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“…Despite the findings from our analyses, no significant correlation between lactic acid and proinflammatory cytokines levels was identified, but some evidence suggests that there is a pathogenic connection between lactic acid and the immune response, with high lactate levels being strongly associated with a poor outcome and severe adverse effects of COVID-19 [39]. In fact, the novel lactate blockers approach is hypothesized to be potentially beneficial for COVID-19 complications [39,40].…”

Section: Discussioncontrasting

confidence: 66%

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

Caterino

Costanzo

Fedele

et al. 2021

IJMS

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COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.

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Section: Discussioncontrasting

confidence: 66%

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

Caterino

Costanzo

Fedele

et al. 2021

IJMS

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“…Since high amounts of lactate production during high-intensity anaerobic exercise can influence NK cells, macrophages, DCs, and cytotoxic T cells, as well as immunological indicators including serum IL-6, it is recommended that other lactate-blocking strategies should be employed in inflammatory therapies, in addition to beta-blockers, for treatment of COVID-19 patients [ 104 ].…”

Section: Lactate–a Key Player In the Inflammatory Responsementioning

confidence: 99%

The Lactate and the Lactate Dehydrogenase in Inflammatory Diseases and Major Risk Factors in COVID-19 Patients

Gupta

2022

Inflammation

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— Lactate dehydrogenase (LDH) is a terminating enzyme in the metabolic pathway of anaerobic glycolysis with end product of lactate from glucose. The lactate formation is crucial in the metabolism of glucose when oxygen is in inadequate supply. Lactate can also be formed and utilised by different cell types under fully aerobic conditions. Blood LDH is the marker enzyme, which predicts mortality in many conditions such as ARDS, serious COVID-19 and cancer patients. Lactate plays a critical role in normal physiology of humans including an energy source, a signaling molecule and a pH regulator. Depending on the pH, lactate exists as the protonated acidic form (lactic acid) at low pH or as sodium salt (sodium lactate) at basic pH. Lactate can affect the immune system and act as a signaling molecule, which can provide a “danger” signal for life. Several reports provide evidence that the serum lactate represents a chemical marker of severity of disease similar to LDH under inflammatory conditions. Since the mortality rate is much higher among COVID-19 patients, associated with high serum LDH, this article is aimed to review the LDH as a therapeutic target and lactate as potential marker for monitoring treatment response of inflammatory diseases. Finally, the review summarises various LDH inhibitors, which offer potential applications as therapeutic agents for inflammatory diseases, associated with high blood LDH. Both blood LDH and blood lactate are suggested as risk factors for the mortality of patients in serious inflammatory diseases.

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“…Lactate is not only a valuable biomarker but also a critical signaling molecule in critical illness, including COVID-19. Thus, it is proposed that both reduced lactate production and inhibition of lactate-mediated signaling could improve COVID-19 ( 194 ). In this context, application of glycolysis inhibitors, such as 2-deoxy-D-glucose (2-DG), may have beneficial effects on COVID-19-infected patients.…”

Section: Discussionmentioning

confidence: 99%

“…We recently reported that blocking lactate influx by MCT1 inhibitor, as well as suppression of GPR81 signaling, decreased HMGB1 release from macrophages ( 13 ). Therefore, similar therapeutic strategies, either inhibition of lactate/GPR81 signaling or block lactate influx by MCT inhibitors, could also be used to abolish the detrimental effects of lactate in SARS-CoV-2 infection ( 194 ). On the other hand, priming the immune system with immunomodulatory components such as glucans may protect cardiovascular dysfunction in COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Dysfunction in COVID-19: Association Between Endothelial Cell Injury and Lactate

et al. 2022

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Coronavirus disease 2019 (COVID-19), an infectious respiratory disease propagated by a new virus known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has resulted in global healthcare crises. Emerging evidence from patients with COVID-19 suggests that endothelial cell damage plays a central role in COVID-19 pathogenesis and could be a major contributor to the severity and mortality of COVID-19. Like other infectious diseases, the pathogenesis of COVID-19 is closely associated with metabolic processes. Lactate, a potential biomarker in COVID-19, has recently been shown to mediate endothelial barrier dysfunction. In this review, we provide an overview of cardiovascular injuries and metabolic alterations caused by SARS-CoV-2 infection. We also propose that lactate plays a potential role in COVID-19-driven endothelial cell injury.

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The potential use of lactate blockers for the prevention of COVID-19 worst outcome, insights from exercise immunology

Cited by 7 publications

References 39 publications

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

The Lactate and the Lactate Dehydrogenase in Inflammatory Diseases and Major Risk Factors in COVID-19 Patients

Cardiovascular Dysfunction in COVID-19: Association Between Endothelial Cell Injury and Lactate

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