Search Results (554)

Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4⁺, CD8⁺, and CD14⁺ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4⁺ and CD14⁺ EV were significantly reduced, while CD8⁺ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell–derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host–parasite interactions. Full article

Despite targeting mainly the respiratory tract, SARS-CoV-2 disrupts T cell homeostasis in ways that may explain both acute lethality and long-term immunological consequences. In this study, we aimed to evaluate the T-cell-mediated chain of immunity and formation of TCR via TREC assessment in COVID-19 and long COVID (LC). For this study, we collected 231 blood samples taken from patients with acute COVID-19 (n = 71), convalescents (n = 51), people diagnosed with LC (n = 63), and healthy volunteers (n = 46). With flow cytometry, we assessed levels of CD4+ and CD8+ minor T cell subpopulations (i.e., naïve, central and effector memory cells (CM and EM), Th1, Th2, Th17, Tfh, Tc1, Tc2, Tc17, Tc17.1, and subpopulations of effector cells (pE1, pE2, effector cells)). Additionally, we measured TREC levels. We found distinct changes in immune cell distribution—whilst distribution of major subpopulations of T cells was similar between cohorts, we noted that COVID-19 was associated with a decrease in naïve Th and CTLs, an increase in Th2/Tc2 lymphocyte polarization, an increase in CM cells, and a decrease in effector memory cells 1,3, and TEMRA cells. LC was associated with naïve CTL increase, polarization towards Th2 population, and a decrease in Tc1, Tc2, Em2, 3, 4 cells. We also noted TREC correlating with naïve cells subpopulations. Our findings suggest ongoing immune dysregulation, possibly driven by persistent antigen exposure or tissue migration of effector cells. The positive correlation between TREC levels and naïve T cells in LC patients points to residual thymic activity. The observed Th2/Th17 bias supports the hypothesis that LC involves autoimmune mechanisms, potentially driven by molecular mimicry or loss of immune tolerance. Full article

Sleep deprivation impairs immune function, and melatonin has emerged as a key mediator in this process. This narrative review analyzes 50 studies published between 2000 and 2025 to determine the extent to which reduced melatonin synthesis contributes to immune dysregulation. Consistent sleep loss lowers melatonin levels, which correlates with elevated proinflammatory cytokines (e.g., IL-6 and TNF-α), increased oxidative stress, and reduced immune cell activity, including that of natural killer (NK) cells and CD4+ lymphocytes. Melatonin regulates immune pathways, including NF-κB signaling. It also supports mitochondrial health and helps maintain gut barrier integrity. These effects are particularly relevant in vulnerable populations, including older adults and shift workers. Experimental findings also highlight melatonin’s therapeutic potential in infections like SARS-CoV-2, where it modulates inflammatory responses and viral entry mechanisms. Despite the heterogeneity of study methodologies, a consistent correlation emerges between circadian disruption, melatonin suppression, and immune imbalance. These findings underscore melatonin’s dual role as a chronobiotic and immunomodulator. Addressing sleep loss and considering melatonin-based interventions may help restore immune homeostasis. More clinical trials are needed to determine the best dosing, long-term efficacy, and population-specific strategies for supplementation. Promoting healthy sleep is crucial for preventing chronic inflammation and diseases associated with immune dysfunction. Full article

Post-viral conditions, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC), share > 95% of their symptoms, but the connection between disturbances in their underlying molecular biology is unclear. This study investigates DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from patients with ME/CFS, LC, and healthy controls (HC). Reduced Representation Bisulphite Sequencing (RRBS) was applied to the DNA of age- and sex-matched cohorts: ME/CFS (n = 5), LC (n = 5), and HC (n = 5). The global DNA methylomes of the three cohorts were similar and spread equally across all chromosomes, except the sex chromosomes, but there were distinct minor changes in the exons of the disease cohorts towards more hypermethylation. A principal component analysis (PCA) analysing significant methylation changes (p < 0.05) separated the ME/CFS, LC, and HC cohorts into three distinct clusters. Analysis with a limit of >10% methylation difference and at p < 0.05 identified 214 Differentially Methylated Fragments (DMF) in ME/CFS, and 429 in LC compared to HC. Of these, 118 DMFs were common to both cohorts. Those in promoters and exons were mainly hypermethylated, with a minority hypomethylated. There were rarer examples with either no change in methylation in ME/CFS but a change in LC, or a methylation change in ME/CFS but in the opposite direction in LC. The differential methylation in a number of fragments was significantly greater in the LC cohort than in the ME/CFS cohort. Our data reveal a generally shared epigenetic makeup between ME/CFS and LC but with specific, distinct changes. Differences between the two cohorts likely reflect the stage of the disease from onset (LC 1 year vs. ME/CFS 12 years), but specific changes imposed by the SARS-CoV-2 virus in the case of the LC patients cannot be discounted. These findings provide a foundation for further studies with larger cohorts at the same disease stage and for functional analyses to establish clinical relevance. Full article

Background/Objectives: The COVID-19 pandemic has caused sickness and death among many health care workers. However, the apparent resistance of health care workers to SARS-CoV-2 infection despite their high-risk work environment remains unclear. To investigate if inflammation and circadian disruption contribute to resistance or diminished susceptibility to the SARS-CoV-2 virus, we retrospectively evaluated a cohort of volunteer hospital nurses (VHNs). Methods: A total of 246 apparently healthy VHNs (mean age 37.4 ± 5.9 years) who had received the BNT162b2 mRNA vaccine were asked to report their sleep quality, according to the Pittsburgh Sleep Quality Index, and number of SARS-CoV-2 infections during the observational study period (from the end of December 2020 to April 2025). The expression of inflammation-associated mediators and circadian transcription factors in peripheral blood mononuclear cells, as well as sleep quality, were examined. Results: Our findings revealed no anthropometric, biochemical, or inflammation-associated parameters but demonstrated significantly greater levels of NFE2L2, also known as nuclear factor erythroid-derived 2-like 2 (NFR2), gene expression in peripheral blood mononuclear cells among VHNs who had never been infected with SARS-CoV-2 (n = 97) than in VHNs with only one (n = 119) or with two or more (n = 35) prior SARS-CoV-2 infections (p < 0.01). This result was confirmed through one-to-one propensity score matching (p < 0.01). Moreover, NRF2 gene expression was not associated with the number of COVID-19 vaccinations (p = 0.598). Finally, NRF2 gene expression was higher among participants who reported better sleep quality (p < 0.01). Conclusions: Our findings suggest possible interactions among NRF2 gene expression, protection against SARS-CoV-2 infection, and the modulation of COVID-19 vaccination efficacy. Full article

The main objective of proton beam therapy is to precisely irradiate diseased tissue while minimizing damage to healthy cells. For effective treatment, the linear energy transfer (LET) is a key parameter in ensuring the destruction of diseased cells, and both the dose and LET are typically represented as functions of depth. The distribution of dose and LET in the target depends on the beam properties, including beam energy, energy spread, beam size, and beam emittance. The aim of this work is to present the method used to characterize the proton beam properties obtained from the machine employed in the simulation and to determine the dose and dose-averaged LET (LET_d) values, including their peak positions in depth. These results are used to predict the dose and LET_d at different depth positions under experimental conditions. We utilized GEANT4, a Monte Carlo (MC) simulation-based software, to examine the integral depth-dose position and the peak position of the LET_d. The proton source was obtained from a cyclotron accelerator, specifically the Varian ProBeam Compact spot scanning system at King Chulalongkorn Memorial Hospital in Bangkok, Thailand. The system provides proton energies ranging from 70 MeV to 220 MeV. In this study, four proton energies—70 MeV, 100 MeV, 150 MeV, and 220 MeV—were chosen to characterize the beam properties. The 80%–20% distal fall-off obtained from the simulation was used to determine the energy spread for each selected energy by matching the depth-dose peak with the measurement data. The optimal energy spreads were found to be 1.5%, 1.25%, 1%, and 0.5% for proton energies of 70 MeV, 100 MeV, 150 MeV, and 220 MeV, respectively. These energy spreads ensure that the difference in the depth-dose profile is below 1% when comparing the simulated and measured depth-dose profiles. Furthermore, the peak LET_d was found to be approximately 1 mm away from the R₈₀ position, a depth that corresponds to 80% of maximum dose, for each energy. This information can be used to guide the desired LET_d position by utilizing the R₈₀ depth position. Full article

The use of postbiotics for dietary fortification in aquaculture is gaining increasing attention due to their potential immunomodulatory and gut health benefits. In this study, we evaluated the effects of postbiotics derived from Vibrio proteolyticus DCF12.2 on intestinal histology, microbiota composition, and the expression of genes related to epithelial integrity and inflammation in juvenile gilthead seabream (Sparus aurata). Fish were fed either a control (CRTL) diet or the postbiotic-supplemented diet (VP) for 62 days. At the end of the feeding trial, a lipopolysaccharide (LPS) challenge was conducted to evaluate the immune response in fish. Histological analysis revealed a healthy mucosa in both groups, though fish fed the VP diet reduced fold height and mucosal layer thickness, alongside a significant increase in goblet cells. Microbiota profiling indicated higher alpha diversity and significant shifts in community composition in the VP group, including enrichment of potentially beneficial genera (Pseudomonas, Sphingomonas) and depletion of opportunistic taxa (Enterococcus, Stenotrophomonas). After the feeding trial, fish fed the VP diet exhibited downregulation of pro-inflammatory markers (tnfα, cox2). Following LPS challenge, cdh1—a key epithelial adhesion protein required for maintaining intestinal barrier integrity—expression was upregulated significantly in the VP group, suggesting enhanced epithelial resilience. These findings demonstrate that dietary fortification with V. proteolyticus-derived postbiotics supports mucosal health as well as modulates the intestinal microbiota and immune responses in gilthead seabream juveniles, offering a promising strategy for functional aquafeed development in sustainable aquaculture. Full article

Background/Objective: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death and tumors with an extremely poor prognosis. In the present study, novel biomarker candidates useful for the early diagnosis and prognosis of human invasive PDAC were investigated. Methods: Biomarker candidates were first selected based on the proteomic/bioinformatic and clinico-pathological analyses of 10 and 100 patients with PDAC, respectively, operated at Osaka Metropolitan University Hospital (Exp. 1). Next, the expression and secretion of the target protein and its EV mRNA were investigated in pancreatic cancer cells in vitro and in a Balb/c nude mouse model. In addition, the protein and EV mRNA levels of candidate molecules were measured in the blood serum of 36 PDAC and 10 IPMN patients, and diagnostic significance was assessed (Exp. 2). Results: A significant elevation of peroxiredoxin 3 (PRX3), a mitochondrial matrix protein, was found in PDAC via LC-Ms/Ms analysis. In Exp. 1, PRX3 overexpression was found in PDAC and PanIN lesions and was associated with a tumor infiltrative growth pattern (INFc) and poor overall 1-year patient survival. The prognostic value was significantly improved when PRX3 was combined with serum SPan-1 and DUPAN-2 markers in survival analyses. Furthermore, the PRX3 protein and its extracellular vesicle (EV: exosome and oncosome)-incorporated mRNA were secreted at detectable levels from PANC-1, MIAPaCa-2, and SW1990 cells into the blood of Balb/c nude mice bearing tumors. The overexpression of PRX3 was positively correlated with that of cancer stem cell marker CD44 variant 9 (CD44v9), P-Nrf2, and FOXO3a, as well as the generation of reactive oxygen species. In Exp. 2, a significant increase in PRX3 protein and EV mRNA was detected in the blood serum of PDAC subjects compared to IPMN patients and healthy controls. Significantly higher PRX3 protein levels were found in the IPMN group. The elevation of PRX3 EV mRNA was significantly associated with poor patient survival. Conclusions: These results indicate that PRX3 may become a novel early biomarker for PDAC diagnosis and prognosis. Full article

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact on public health continue to demand attention as the virus continues to evolve, demonstrating a remarkable ability to adapt to diverse selective pressures including immune responses, therapeutic treatments, and prophylactic interventions. The SARS-CoV-2 variant landscape remains dynamic, with new subvariants continuously emerging, many harboring spike protein mutations linked to immune evasion. In this study, we characterized a panel of live SARS-CoV-2 strains, including those key subvariants implicated in recent waves of infection. Our findings revealed a significant variability in mutation patterns in the spike protein across the strains analyzed. Commercial antibodies and human convalescent plasma (HCoP) samples from unvaccinated donors were ineffective in neutralizing the most recent Omicron subvariants, particularly after the emergence of JN.1 subvariant. Using human airway epithelial cells derived from healthy bronchiolar tissue (hBAEC), we established both monoinfections and coinfections involving SARS-CoV-2, Influenza A virus H1N1 (IFAV_H1N1) and Respiratory Syncytial Virus (RSV). Assessments were conducted to compare viral infectivity and the production and release of immune mediators in the apical and basolateral compartments. Notably, Omicron KP.3.1.1 subvariant induced a more pronounced cytopathic effect in hBAEC compared to its parental strain JN.1 and even surpassed the impact observed with the ancestral wild-type virus (WA1/2020, Washington strain). Furthermore, the coinfection of KP.3.1.1 subvariant with IFAV_H1N1 or RSV did not attenuate SARS-CoV-2 infectivity; instead, it significantly exacerbated the pathogenic synergy in the lung epithelium. Our study demonstrated that pro-inflammatory cytokines IL-6, IFN-β, and IL-10 were upregulated in hBAEC following SARS-CoV-2 monoinfection with recent Omicron subvariants as well as during coinfection with IFAV_H1N1 and RSV. Taken together, our findings offer new insights into the immune evasion strategies and pathogenic potential of evolving SARS-CoV-2 Omicron subvariants, as well as their interactions with other respiratory viruses, carrying important implications for therapeutic development and public health preparedness. Full article

HIKESHI-related hypomyelinating leukodystrophy (HHL) is a life-threatening disorder caused by homozygous pathogenic variants in HIKESHI. Symptoms include infantile onset progressive spastic dystonic quadriplegia, nystagmus, failure to thrive, diffused hypomyelination, and severe morbidity or death following febrile illness. V54L variants in HIKESHI are particularly prevalent within the Ashkenazi Jewish population. Here, we identified a novel P78S disease-causing variant in HIKESHI in a patient of Christian Arab origin, presenting with clinical and radiologic features characteristic of HHL. In silico analysis suggests that the mutated residue may affect the HIKESHI protein’s dimerization domain. We generated a comprehensive set of induced pluripotent stem cells (iPSCs) from the index case and two additional HHL patients. To investigate mechanisms potentially linked to febrile illness in HHL, we used these cells to study the heat shock (HS) response. HHL-iPSCs showed dramatically decreased levels of HIKESHI compared with healthy controls following HS. In addition, they exhibited increased HSP70 mRNA levels in response to HS, suggesting an increased sensitivity. HHL-iPSCs had impaired HSP70 translocation to the nucleus. Our results provide a human-relevant model for HHL. Full article

Objectives: Patients with interstitial lung disease (ILD) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at high risk of severe coronavirus disease 2019. It is unclear whether anti-viral cellular and humoral immunity is impacted in patients with ILD in the presence of immune disorders and immunosuppressive therapy. This results in poor control of viral infections following SARS-CoV-2 infection. We aimed to highlight the clinical management of patients with ILD with regard to the adjustment of anti-inflammatory therapy during SARS-CoV-2 infection. Methods: We compared viral clearance, antibody levels, and T-cell immune response between healthy controls and patients with connective tissue disease-related ILD (CTD-ILD) or interstitial pneumonia with autoimmune features (IPAF). Results: Patients with ILD exhibited a higher viral load than the control group (1.58 × 10⁶ vs. 2.37 × 10³ copies/mL, p = 0.018), as well as a significantly lower level of neutralizing antibodies against the wild-type (WT) virus (7.01 vs. 625.6, p < 0.0001) and Omicron BA.5 (7.19 vs. 128.4, p < 0.001). Similarly, a lower virus-specific T-cell (VST) immune response was observed 14 days post-symptom onset in the ILD group (CD4⁺ VSTs: 0.018 vs. 0.082, p = 0.005; CD8⁺ VSTs: 0.0008 vs. 0.047, p = 0.004). The ILD group had no other heightened inflammatory biomarkers compared with the control group. Conclusions: Our study provides novel evidence of the underlying interaction between virus clearance and host immune status and sheds light on the clinical management of patients with ILD with regard to the adjustment of anti-inflammatory therapy during SARS-CoV-2 infection. Full article

There is a growing interest in using agri-food by-products and a demand for natural substances that might help maintain healthy honey bee colonies. We investigated a by-product of the wine industry, a grape pomace (GP) of the autochthonous Prokupac grape cultivar from Serbia. A hydroethanolic extract (50% (w/v) ethanol) of GP (Prokupac GP extract) obtained by the pressurized liquid extraction (PLE) method was subjected to qualitative profiling of phenolic composition by liquid chromatography with OrbiTrap Exploris 120 mass spectrometer. Then, the extracts’ antioxidant and redox-modulatory activities were evaluated through Electron Paramagnetic Resonance (EPR) spectroscopy. Finally, the extract’s potential to modulate cellular redox status was evaluated using cultured AmE-711 honey bee cells. The results show that the Prokupac GP extract contains a wide array of flavonoids, anthocyanins, stilbenes, and their various conjugated derivatives and that anthocyanins, particularly malvidin-based compounds, dominate. EPR measurements showed strong scavenging activity against superoxide anion (O₂^•−) and hydroxyl radicals (^•OH), with inhibition efficiencies of 84.37% and 81.81%, respectively, while activity against the DPPH radical was lower (17.75%). In the cell-based assay, the Prokupac GP extract consistently provided strong antioxidant protection and modulated the cellular response to oxidative stress by over 14%. In conclusion, while the Prokupac GP extract demonstrated antioxidant properties and the ability to modulate cellular responses to oxidative stress, in vivo studies on honey bees are required to confirm its efficacy and safety for potential use in beekeeping practice. Full article

In poultry production, antibiotics have been excessively used as growth promoters to support well-being and decrease mortality caused by pathogenic microorganisms. The overuse of antibiotics has led to the emergence of antibiotic-resistant bacteria and the presence of antibiotic residues in poultry products. To counteract this problem, probiotics could be used as adjuncts or as substitutes for preserving a diverse and balanced microflora to prevent the colonization and multiplication of pathogenic bacteria in the GI tract. This study aimed to isolate and characterize the potential probiotic properties of lactic acid bacteria from the small intestine of 23-week-old broiler breeders, with the goal of identifying potential probiotic candidates. Four phenotypically healthy broiler breeders were selected, and intestinal contents were aseptically collected and cultured on MRS agar. From the initial pool of 39 colonies, six isolates were identified based on Gram-positive and catalase-negative characteristics and further classified using 16S rRNA sequencing as Levilactobacillus brevis (n = 3), Pediococcus pentosaceus (n = 2), and Streptococcus salivarius (n = 1). These strains were further evaluated for probiotic properties such as transit resistance to simulated upper gastrointestinal conditions, antagonist activity, haemolytic activity, and cell surface properties such as autoaggregation, co-aggregation and hydrophobicity, in vitro. L. brevis NKFS8 showed good tolerance to pH 3, while P. pentosaceus NKSF10 exhibited good tolerance to pH 4 acidic conditions. All isolates demonstrated good survivability in bile salt concentration of 3% (w/v), with P. pentosaceus NKSF10 exhibiting the highest tolerance. The isolates showed a wide range of antagonistic activity against the test pathogens Pseudomonas aeruginosa (ATCC 27853), Salmonella typhimurium, Salmonella enterica (ATCC 13314), Staphylococcus aureus (ATCC 29213), and Listeria monocytogenes (ATCC 7644). Furthermore, these strains exhibited good auto-aggregation, co-aggregation, and hydrophobicity properties. In conclusion, lactic acid bacteria from the small intestine of broiler breeders present a valuable prospect for the development of effective probiotics. These probiotics can be utilized as a supplementary inclusion in poultry feed, obviating the need for antibiotics as growth promoters. Nevertheless, additional in vivo studies are required to closely monitor and assess the effects of probiotics on the gastrointestinal system of chickens. Full article

Environmental pollution by heavy metals (HMs) has become a serious threat in recent years due to their potential consequences for human health and life. One such metal is vanadium (V). Despite its numerous benefits—including antibacterial, antifungal, and anticancer properties—V induces cellular damage through oxidative stress. Epigallocatechin gallate (EGCG), a potent antioxidant found in large quantities in green tea, is considered an effective protector against the damaging effects of HMs on cells. The aim of this study was to evaluate the possible effect of EGCG on CHO-K1 cells exposed to V. This is the first experiment of its kind on healthy cells. Cells were treated with V and EGCG for 24 h, either in combination or separately. The doses were selected in a preliminary stage of the experiment (V 50 and 100 µM; EGCG 0.5 and 1 µM). As part of the study, the cell viability, total ROS activity, and mitochondrial membrane potential were assessed. The results showed that at the tested concentrations, EGCG did not reduce the toxic effect of V on cells, but in fact exacerbated its adverse effects on cells. Further studies are needed to understand the exact mechanism of V–EGCG interaction in mammalian cells. Full article

Cardiovascular complications are a hallmark of Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC), yet the mechanisms driving persistent cardiac dysfunction remain poorly understood. Emerging evidence implicates mitochondrial dysfunction in immune cells as a key contributor. This study investigated whether CD14⁺⁺ monocytes from long COVID patients exhibit bioenergetic impairment, mitochondrial DNA (mtDNA) damage, and defective oxidative stress adaptation, which may underlie cardiovascular symptoms in PASC. CD14⁺⁺ monocytes were isolated from 14 long COVID patients with cardiovascular symptoms (e.g., dyspnea, angina) and 10 age-matched controls with similar cardiovascular risk profiles. Mitochondrial function was assessed using a Seahorse Agilent Analyzer under basal conditions and after oxidative stress induction with buthionine sulfoximine (BSO). Mitochondrial membrane potential was measured via Tetramethylrhodamine Ethyl Ester (TMRE) assay, mtDNA integrity via qPCR, and reactive oxygen species (ROS) dynamics via Fluorescence-Activated Cell Sorting (FACS). Parallel experiments exposed healthy monocytes to SARS-CoV-2 spike protein to evaluate direct viral effects. CD14⁺⁺ monocytes from long COVID patients with cardiovascular symptoms (n = 14) exhibited profound mitochondrial dysfunction compared to age-matched controls (n = 10). Under oxidative stress induced by buthionine sulfoximine (BSO), long COVID monocytes failed to upregulate basal respiration (9.5 vs. 30.4 pmol/min in controls, p = 0.0043), showed a 65% reduction in maximal respiration (p = 0.4035, ns) and demonstrated a 70% loss of spare respiratory capacity (p = 0.4143, ns) with significantly impaired adaptation to BSO challenge (long COVID + BSO: 9.9 vs. control + BSO: 54 pmol/min, p = 0.0091). Proton leak, a protective mechanism against ROS overproduction, was blunted in long COVID monocytes (3-fold vs. 13-fold elevation in controls, p = 0.0294). Paradoxically, long COVID monocytes showed reduced ROS accumulation after BSO treatment (6% decrease vs. 1.2-fold increase in controls, p = 0.0015) and elevated mitochondrial membrane potential (157 vs. 113.7 TMRE fluorescence, p = 0.0179), which remained stable under oxidative stress. mtDNA analysis revealed severe depletion (80% reduction, p < 0.001) and region-specific damage, with 75% and 70% reductions in amplification efficiency for regions C and D (p < 0.05), respectively. In contrast, exposure of healthy monocytes to SARS-CoV-2 spike protein did not recapitulate these defects, with preserved basal respiration, ATP production, and spare respiratory capacity, though coupling efficiency under oxidative stress was reduced (p < 0.05). These findings suggest that mitochondrial dysfunction in long COVID syndrome arises from maladaptive host responses rather than direct viral toxicity, characterized by bioenergetic failure, impaired stress adaptation, and mitochondrial genomic instability. This study identifies persistent mitochondrial dysfunction in long COVID monocytes as a critical driver of cardiovascular complications in PASC. Key defects—bioenergetic failure, impaired stress adaptation and mtDNA damage—correlate with clinical symptoms like heart failure and exercise intolerance. The stable elevation of mitochondrial membrane potential and resistance to ROS induction suggest maladaptive remodeling of mitochondrial physiology. These findings position mitochondrial resilience as a therapeutic target, with potential strategies including antioxidants, mtDNA repair agents or metabolic modulators. The dissociation between spike protein exposure and mitochondrial dysfunction highlights the need to explore host-directed mechanisms in PASC pathophysiology. This work advances our understanding of long COVID cardiovascular sequelae and provides a foundation for biomarker development and targeted interventions to mitigate long-term morbidity. Full article