COVID-19 Complications: Oxidative Stress, Inflammation, and Mitochondrial and Endothelial Dysfunction

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14876 - 14876

Published: Oct. 4, 2023

SARS-CoV-2 infection, discovered and isolated in Wuhan City, Hubei Province, China, causes acute atypical respiratory symptoms has led to profound changes our lives. COVID-19 is characterized by a wide range of complications, which include pulmonary embolism, thromboembolism arterial clot formation, arrhythmias, cardiomyopathy, multiorgan failure, more. The disease caused worldwide pandemic, despite various measures such as social distancing, preventive strategies, therapeutic approaches, the creation vaccines, novel coronavirus infection (COVID-19) still hides many mysteries for scientific community. Oxidative stress been suggested play an essential role pathogenesis COVID-19, determining free radical levels patients with may provide insight into severity. generation abnormal oxidants under COVID-19-induced cytokine storm irreversible oxidation macromolecules subsequent damage cells, tissues, organs. Clinical studies have shown that oxidative initiates endothelial damage, increases risk complications post-COVID-19 or long-COVID-19 cases. This review describes radicals mediation mitochondrial dysfunction.

Language: Английский

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Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized controlled trial

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 26, 2023

The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy their derivatives can be used to relieve inflammation these cases. In this study, we aimed evaluate the safety efficacy using mesenchymal stromal cells (MSCs) derived extracellular vesicles COVID-19 patients.

Language: Английский

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Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(4), P. e244386 - e244386

Published: April 4, 2024

Importance Many patients with post-COVID condition (PCC) experience persistent fatigue, muscle pain, and cognitive problems that worsen after exertion (referred to as postexertional malaise). Recommendations currently advise against exercise in this population prevent symptom worsening; however, prolonged inactivity is associated risk of long-term health deterioration. Objective To assess symptoms PCC compared control participants comprehensively investigate the physiologic mechanisms underlying PCC. Design, Setting, Participants In randomized crossover clinical trial, nonhospitalized without concomitant diseases (≥3 months) symptoms, including malaise, SARS-CoV-2 infection were recruited Sweden from September 2022 July 2023. Age- sex-matched also recruited. Interventions After comprehensive characterization, completed 3 trials (high-intensity interval training [HIIT], moderate-intensity continuous [MICT], strength [ST]) a order. Symptoms reported at baseline, immediately exercise, 48 hours exercise. Main Outcomes Measures The primary outcome was between-group differences changes fatigue baseline assessed via visual analog scale (VAS). Questionnaires, cardiopulmonary testing, inflammatory markers, characterization provided information on function Results Thirty-one (mean [SD] age, 46.6 [10.0] years; 24 [77%] women) 31 healthy 47.3 [8.9] 23 [74%] included. Patients more than controls all time points. However, there no difference between groups worsening response different exercises VAS ranks for HIIT: PCC, 29.3 [19.5]; controls, 28.7 [11.4]; P = .08; MICT: 31.2 [17.0]; 24.6 [11.7]; .09; ST: 31.0 [19.7]; 28.1 [12.2]; .49). had greater exacerbation pain HIIT ranks, 33.4 [17.7] vs 25.0 [11.3]; .04) concentration difficulties MICT 33.0 [17.1] 23.3 [10.6]; .03) controls. At showed preserved lung heart but 21% lower peak volume oxygen consumption difference: −6.8 mL/kg/min; 95% CI, −10.7 −2.9 < .001) less isometric knee extension −37 Nm; −67 −7 .02) spent 43% moderate vigorous physical activity difference, −26.5 minutes/d; −42.0 −11.1 .001). Of note, 4 (13%) postural orthostatic tachycardia, 18 29 (62%) signs myopathy determined by neurophysiologic testing. Conclusions Relevance study, generally tolerated cardiovascular aerobic capacity group. They tachycardia myopathy. findings suggest cautious adoption could be recommended further skeletal deconditioning impairment Trial Registration ClinicalTrials.gov Identifier: NCT05445830

Language: Английский

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Early prediction of long COVID-19 syndrome persistence at 12 months after hospitalisation: a prospective observational study from Ukraine

BMJ Open, Journal Year: 2025, Volume and Issue: 15(1), P. e084311 - e084311

Published: Jan. 1, 2025

To identify the early predictors of a self-reported persistence long COVID syndrome (LCS) at 12 months after hospitalisation and to propose prognostic model its development. A combined cross-sectional prospective observational study. tertiary care hospital. 221 patients hospitalised for COVID-19 who have undergone comprehensive clinical, sonographic survey-based evaluation predischarge 1 month with subsequent 12-month follow-up. The final cohort included 166 had completed visit months. LCS discharge. Self-reported was detected in 76% participants 3 43% Patients reported incomplete recovery year were characterised by higher burden comorbidities (Charlson index 0.69±0.96 vs 0.31±0.51, p=0.001) residual pulmonary consolidations (1.56±1.78 0.98±1.56, p=0.034), worse blood pressure (BP) control (systolic BP 138.1±16.2 132.2±15.8 mm Hg, p=0.041), renal (estimated glomerular filtration rate 59.5±14.7 69.8±20.7 mL/min/1.73 m2, p=0.007) endothelial function (flow-mediated dilation brachial artery 10.4±5.4 12.4±5.6%, p=0.048), in-hospital levels liver enzymes (alanine aminotransferase (ALT) 76.3±60.8 46.3±25.3 IU/L, p=0.002) erythrocyte sedimentation (ESR) (34.3±12.1 28.3±12.6 mm/h, p=0.008), slightly indices ventricular longitudinal (left (LV) global strain (GLS) 18.0±2.4 17.0±2.3%, p=0011) Hospital Anxiety Depression Scale anxiety (7.3±4.2 5.6±3.8, p=0.011) depression scores (6.4±3.9 4.9±4.3, p=0.022) EFTER-COVID study physical symptoms score (12.3±3.8 9.2±4.2, p<0.001). At postdischarge, persisting differences marginally LV GLS, mitral E/e' ratio significantly both resting exertional versus complete recovery. Logistic regression machine learning-based binary classification models been developed predict Compared post-COVID-19 completely recovered hospital discharge, those subsequently 'very long' variety more pronounced abnormalities that mostly subsided month, except steady levels. simple artificial neural networks-based using peak ESR, creatinine, ALT weight loss during acute phase, 6-minute walk distance complex assessment as inputs has shown 92% accuracy an area under receiver-operator characteristic curve 0.931 prediction

Language: Английский

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Modeling Heart Diseases on a Chip: Advantages and Future Opportunities

Circulation Research, Journal Year: 2023, Volume and Issue: 132(4), P. 483 - 497

Published: Feb. 16, 2023

Heart disease is a significant burden on global health care systems and leading cause of death each year. To improve our understanding heart disease, high quality models are needed. These will facilitate the discovery development new treatments for disease. Traditionally, researchers have relied 2D monolayer or animal to elucidate pathophysiology drug responses. Heart-on-a-chip (HOC) technology an emerging field where cardiomyocytes among other cell types in can be used generate functional, beating cardiac microtissues that recapitulate many features human heart. HOC showing great promise as modeling platforms poised serve important tools pipeline. By leveraging advances pluripotent stem cell-derived cardiomyocyte biology microfabrication technology, diseased HOCs highly tuneable generated via different approaches such as: using cells with defined genetic backgrounds (patient-derived cells), adding small molecules, modifying cells' environment, altering ratio/composition microtissues, others. been faithfully model aspects arrhythmia, fibrosis, infection, cardiomyopathies, ischemia, name few. In this review, we highlight recent systems, describing instances these outperformed terms reproducing phenotypes and/or led development.

Language: Английский

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SARS-CoV-2 and the spike protein in endotheliopathy

Trends in Microbiology, Journal Year: 2023, Volume and Issue: 32(1), P. 53 - 67

Published: June 12, 2023

Language: Английский

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Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 10, 2023

Many patients with SARS-CoV-2 infection develop long COVID fatigue as one of the most disabling symptoms. We performed clinical and immune profiling fatigued non-fatigued age- sex-matched healthy controls (HCs).Long symptoms were assessed using patient-reported outcome measures, including assessment scale (FAS, scores ≥22 denote fatigue), followed up to year after hospital discharge. inflammation-related genes in circulating monocytes, serum levels inflammation-regulating cytokines, leukocyte lymphocyte subsets, major monocyte subsets senescent T-lymphocytes, at 3-6 months post-discharge.We included 37 36 42 HCs. Fatigued represented a more severe profile than patients, many concurrent (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p<0.001), signs cognitive failure (41%) depression (>24%). Immune abnormalities that found entire group low grade inflammation (increased inflammatory gene expression increased pro-inflammatory cytokines) T-lymphocyte senescence exhausted CD8+ TEMRA-lymphocytes). profiles did not significantly differ between groups. However, severity (total FAS score) correlated increases intermediate non-classical upregulated CCL2, CCL7, SERPINB2 Galectin-9, higher counts.Long is associated persistent lasting hospitalization. Increased stronger activation potentially point direction monocyte-endothelial interaction. These present against background common patients.

Language: Английский

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Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation

Angiogenesis, Journal Year: 2023, Volume and Issue: 26(4), P. 547 - 563

Published: July 28, 2023

Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in high impact on the daily life of patients. Understanding pathophysiology PCS public health priority, it still poses diagnostic treatment challenge for physicians.In this prospective observational cohort study, we analyzed retinal microcirculation using Retinal Vessel Analysis (RVA) patients compared to an age- gender-matched healthy (n = 41, matched out n 204).PCS exhibit persistent endothelial dysfunction (ED), indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% 2.59%; p 0.02), narrower central artery equivalent (CRAE; 178.1 [167.5-190.2] 189.1 [179.4-197.2], 0.01) arteriolar-venular ratio (AVR; (0.84 [0.8-0.9] 0.88 [0.8-0.9], 0.007). When combining AVR vFID, predicted scores reached good ability discriminate groups (area under curve: 0.75). Higher severity correlated (R - 0.37 0.017). The association microvascular changes were amplified exhibiting higher levels inflammatory parameters.Our results demonstrate that prolonged hallmark PCS, impairments seem explain As potential therapies emerge, RVA parameters may become relevant clinical biomarkers diagnosis therapy management.This study was previously registered at ClinicalTrials ("All Eyes PCS-Analysis Microvasculature Patients Syndrome". NCT05635552. https://clinicaltrials.gov/ct2/show/NCT05635552 ). Persistent post-COVID-19 syndrome. Acute SARS-CoV-2 infection indirectly or directly causes endotheliitis N 41 recruited vessel analysis performed assess function. Images SVA DVA are illustrative data analysis. For each patient cohort, diameter three measurement cycles calculated plotted diameter-time curve. exhibited reduced veins (vFID) measured dynamic (DVA) arteriolar (CRAE) (AVR) tendency towards (CRVE) when naïve participants. Created BioRender.com.

Language: Английский

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Microvascular Thrombosis as a Critical Factor in Severe COVID-19

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2492 - 2492

Published: Jan. 27, 2023

Platelet-endothelial interactions have a critical role in microcirculatory function, which maintains tissue homeostasis. The subtle equilibrium between platelets and the vessel wall is disturbed by coronavirus disease 2019 (COVID-19), affects all three components of Virchow's triad (endothelial injury, stasis hypercoagulable state). Endotheliitis, vasculitis, glycocalyx degradation, alterations blood flow viscosity, neutrophil extracellular trap formation microparticle shedding are only few pathomechanisms contributing to endothelial damage microthrombosis resulting capillary plugging ischemia. In following opinion paper, we discuss major pathological processes leading microvascular activation thrombosis as possible adverse factor driving deterioration patient course severe COVID-19.

Language: Английский

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Influence of Immune System Abnormalities Caused by Maternal Immune Activation in the Postnatal Period

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 741 - 741

Published: Feb. 25, 2023

The developmental origins of health and disease (DOHaD) indicate that fetal tissues organs in critical sensitive periods development are susceptible to structural functional changes due the adverse environment utero. Maternal immune activation (MIA) is one phenomena DOHaD. Exposure maternal a risk factor for neurodevelopmental disorders, psychosis, cardiovascular diseases, metabolic human disorders. It has been associated with increased levels proinflammatory cytokines transferred from mother fetus prenatal period. Abnormal immunity induced by MIA includes overreaction or response failure offspring. Immune hypersensitivity system pathogens allergic factor. could not properly fight off various pathogens. clinical features offspring depend on gestation period, inflammatory magnitude, type exposure stimulation, which might induce epigenetic modifications system. An analysis caused intrauterine environments allow clinicians predict onset diseases disorders before after birth.

Language: Английский

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