Signatures of Mitochondrial Dysfunction and Impaired Fatty Acid Metabolism in Plasma of Patients with Post-Acute Sequelae of COVID-19 (PASC)

Metabolites, Год журнала: 2022, Номер 12(11), С. 1026 - 1026

Опубликована: Окт. 26, 2022

Exercise intolerance is a major manifestation of post-acute sequelae severe acute respiratory syndrome coronavirus infection (PASC, or "long-COVID"). in PASC associated with higher arterial blood lactate accumulation and lower fatty acid oxidation rates during graded exercise tests to volitional exertion, suggesting altered metabolism mitochondrial dysfunction. It remains unclear whether the profound disturbances that have been identified plasma from patients suffering disease 2019 (COVID-19) are also present PASC. To bridge this gap, individuals history previous COVID-19 did not require hospitalization were enrolled at National Jewish Health (Denver, CO, USA) grouped into those developed (n = 29) fully recovered 16). Plasma samples two groups analyzed via mass spectrometry-based untargeted metabolomics compared against metabolic profiles healthy control 30). Observational demographic clinical data retrospectively abstracted medical record. Compared controls who COVID-19, exhibited significantly free- carnitine-conjugated mono-, poly-, highly unsaturated acids, accompanied by markedly levels di- tricarboxylates (pyruvate, lactate, citrate, succinate, malate), polyamines (spermine) taurine. an intermediary phenotype, milder spermine Of note, depletion tryptophan-a hallmark severity COVID-19-is normalized patients, despite normalization kynurenine levels-a tryptophan metabolite predicts mortality hospitalized patients. In conclusion, metabolites indicative dysfunctional mitochondria-dependent lipid catabolism. These obtained rest consistent previously reported dysfunction exercise, may pave way for therapeutic intervention focused on restoring fat-burning capacity.

Язык: Английский

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The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Biochemical Journal, Год журнала: 2022, Номер 479(16), С. 1653 - 1708

Опубликована: Авг. 31, 2022

Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety acute circumstances. We argue here that I-R injury also underpins elements pathology chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be fibrin amyloid microclot blockage capillaries, for instance as exercise started; reperfusion necessary corollary when it finishes. rehearse mechanistic evidence these occurrences here, terms their manifestation oxidative stress, hyperinflammation, mast cell activation, production marker metabolites related activities. Such microclot-based phenomena can explain both breathlessness/fatigue post-exertional malaise observed conditions, many other observables. The recognition processes implies, mechanistically, therapeutic benefit potentially to had from antioxidants, anti-inflammatories, iron chelators, suitable, safe fibrinolytics, and/or anti-clotting agents. review considerable existing consistent with this, biochemical mechanisms involved.

Язык: Английский

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Hemolytic anemia in COVID-19

Annals of Hematology, Год журнала: 2022, Номер 101(9), С. 1887 - 1895

Опубликована: Июль 8, 2022

Язык: Английский

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Coagulation Disorders in Sepsis and COVID-19—Two Sides of the Same Coin? A Review of Inflammation–Coagulation Crosstalk in Bacterial Sepsis and COVID-19

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(2), С. 601 - 601

Опубликована: Янв. 11, 2023

Sepsis is a major cause of morbidity and mortality worldwide. Sepsis-associated coagulation disorders are involved in the pathogenesis multiorgan failure lead to subsequently worsening prognosis. Alongside global impact COVID-19 pandemic, great number research papers have focused on SARS-CoV-2 treatment. Significant progress has been made this regard disturbances were once again found underlie some most serious adverse outcomes infection, such as acute lung injury dysfunction. In attempt untangling mechanisms behind COVID-19-associated coagulopathy (CAC), series similarities with sepsis-induced (SIC) became apparent. Whether they are, fact, same disease not established yet. The clinical picture CAC shows unique feature an initial phase intravascular confined respiratory system. Only later on, patients can develop clinically significant form systemic coagulopathy, possibly consumptive pattern, but, unlike SIC, it key feature. Deepening our understanding remain goal for community, order design validate accurate definitions classification criteria.

Язык: Английский

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Hematological alterations associated with long COVID-19

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Июль 24, 2023

Long COVID-19 is a condition characterized by persistent symptoms lasting beyond the acute phase of COVID-19. produces diverse symptomatology and can impact organs systems, including hematological system. Several studies have reported, in patients, abnormalities. Most these alterations are associated with higher risk severe disease poor outcomes. This literature review identified reporting parameters individuals Findings suggest that range sustained alterations, red blood cells, anemia, lymphopenia, elevated levels inflammatory markers such as ferritin, D-dimer, IL-6. These may contribute to better understanding pathophysiology its symptoms. However, further research needed elucidate underlying mechanisms potential treatments for changes

Язык: Английский

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Long COVID: a narrative review of the clinical aftermaths of COVID-19 with a focus on the putative pathophysiology and aspects of physical activity

Oxford Open Immunology, Год журнала: 2022, Номер 3(1)

Опубликована: Янв. 1, 2022

The pandemic coronavirus disease 2019 (COVID-19) can cause multi-systemic symptoms that persist beyond the acute symptomatic phase. post-acute sequelae of COVID-19 (PASC), also referred to as long COVID, describe persistence and/or long-term complications 4 weeks from onset and are estimated affect at least 20% individuals infected with SARS-CoV-2 regardless their severity. multi-faceted clinical picture COVID encompasses a plethora undulating manifestations impacting various body systems such fatigue, headache, attention disorder, hair loss exercise intolerance. physiological response testing is characterized by reduced aerobic capacity, cardiocirculatory limitations, dysfunctional breathing patterns an impaired ability extract use oxygen. Still, this day, causative pathophysiological mechanisms remain be elucidated, organ damage, immune system dysregulation endotheliopathy being among hypotheses discussed. Likewise, there still paucity treatment options evidence-based strategies for management symptoms. In sum, review explores different aspects maps literature on what known about its manifestations, potential mechanisms, options.

Язык: Английский

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Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 4, 2023

Abstract The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways critically ill adults compared to non-COVID using a multiomics approach. Mechanistic in-vitro studies, microvasculature-on-chip devices, reveal that plasma from induces fibrinogen-dependent red blood cell aggregation mechanically damages glycocalyx. This mechanism appears unique COVID-19, sepsis patients demonstrates greater membrane stiffness but less significant overall rheology. Multiomics analyses pediatric or post-infectious multi-inflammatory syndrome children (MIS-C) demonstrate little overlap cytokine metabolite changes adult patients. Instead, MIS-C strongly upregulation. These findings link high fibrinogen endotheliopathy highlight differences key mediators between populations.

Язык: Английский

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Advances in Microfluidics for Single Red Blood Cell Analysis

Biosensors, Год журнала: 2023, Номер 13(1), С. 117 - 117

Опубликована: Янв. 9, 2023

The utilizations of microfluidic chips for single RBC (red blood cell) studies have attracted great interests in recent years to filter, trap, analyze, and release erythrocytes various applications. Researchers this field highlighted the vast potential developing micro devices industrial academia usages, including lab-on-a-chip organ-on-a-chip systems. This article critically reviews current state-of-the-art advances microfluidics analyses, integrated sensors platforms microscopic/tomographic/spectroscopic trapping arrays (including bifurcating channels), dielectrophoretic agglutination/aggregation studies, as well clinical implications covering cancer, sepsis, prenatal, Sickle Cell diseases. Microfluidics based microarrays, sorting/counting techniques acoustic, dielectrophoretic, hydrodynamic, magnetic, optical techniques) are also reviewed. Lastly, organs on chips, multi-organ drug discovery involving described. limitations drawbacks each technology addressed future prospects discussed.

Язык: Английский

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The oxygen dissociation curve of blood in COVID-19–An update

Frontiers in Medicine, Год журнала: 2023, Номер 10

Опубликована: Фев. 27, 2023

An impressive effect of the infection with SARS-Co-19 is impairment oxygen uptake due to lung injury. The reduced diffusion may potentially be counteracted by an increase in affinity hemoglobin. However, hypoxia and anemia associated COVID-19 usually decrease a rise [2,3-bisphosphoglycerate]. As such, related changes dissociation curve critical for supply, but are hard predict. A Pubmed search lists 14 publications on COVID-19. While some investigations show no changes, three large studies found increased that was good prognosis. Exact causes remain unknown. cause under discussion. Erythrocytes structural alterations membrane cytoskeleton have been observed, virus binding Band 3 also ACE2 receptors erythroblasts has proposed. presentation moderate many subjects suffering from sickle cell disease. possible explanation counteracts unfavorable right shift these patients. Under discussion therapy mainly affinity-increasing drugs.

Язык: Английский

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COVID-19 and Anemia: What Do We Know So Far?

Hemoglobin, Год журнала: 2023, Номер 47(3), С. 122 - 129

Опубликована: Май 4, 2023

On 11 March 2020, the World Health Organization (WHO) declared novel SARS-CoV-2 virus responsible for causing COVID-19, a global pandemic. The primarily targets respiratory system but can also affect other systems, notably hematological pathologies. Anemia, common hematologic disorder, is characterized by reduced oxygen-carrying capacity of red blood cells. existing literature has suspected link between anemia and severe COVID-19 cases. Researchers are currently investigating long-term complications in anemic patients, as these may play crucial role predicting patient prognosis. Anemic individuals at higher risk experiencing infections due to several contributing pathophysiological mechanisms, including thrombotic, hemorrhagic, autoimmune etiologies. primary effect mechanisms decrease circulating hemoglobin levels, reducing oxygen availability This exacerbates hypoxia caused COVID-19-induced acute distress syndrome (ARDS). review offers comprehensive overview evidence regarding patients.

Язык: Английский

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