Post-acute sequelae of SARS-CoV-2 infection (long COVID) present with persistent fatigue, cognitive impairment, and autonomic and multisystem dysfunctions that often go unnoticed by standard diagnostic tests. Increasing evidence suggests that mitochondrial dysfunction and oxidative stress are central drivers of these post-viral sequelae. Viral infections, particularly SARS-CoV-2, disrupt mitochondrial bioenergetics by altering membrane integrity, increasing mitochondrial reactive oxygen species (mtROS), and impairing mitophagy, leading to sustained immune activation and metabolic imbalance. This review synthesizes an understanding of how mitochondrial redox signaling and impaired clearance of damaged mitochondria contribute to chronic inflammation and multisystem organ symptoms in both long COVID and post-vaccine injury. We discuss translational biomarkers and non-invasive techniques, exploring therapeutic strategies that include pharmacological, non-pharmacological, and nutritional approaches, as well as imaging modalities aimed at assessing and restoring mitochondrial health. Recognizing long COVID as a mitochondrial disorder that stems from redox imbalance will open new options for personalized treatment and management guided by biomarkers. Future clinical trials are essential to validate these approaches and translate mitochondrial resuscitation into effective care for patients suffering from long COVID and related post-viral syndromes.

Background: Septic shock is a heterogeneous syndrome with diverse clinical presentations and pathophysiology, yet current management guidelines largely treat it as a homogenous entity. Early risk stratification relies on lactate and different predictive scoring systems, which may not capture the underlying heterogeneity in host responses. Aim: To identify discrete subphenotypes of septic shock using admission demographics and laboratory parameters, and to evaluate their relationship with in-hospital outcomes. Methods: We conducted a retrospective multicenter cohort study of 10,462 adult patients with ICD-10-defined septic shock admitted to intensive care units between 2014 and 2015. We used Two-Step Cluster Analysis using log-likelihood distance and the Bayesian Information Criterion to identify two distinct phenotypes. We compared clusters on baseline characteristics, in-hospital outcomes including mortality, days on mechanical ventilation, vasopressor use, acute kidney injury (AKI), AKI requiring renal replacement therapy (RRT), and ICU and hospital lengths of stay. Results: We identified two clusters (Cluster 1, n = 5355 and Cluster 2, n = 5107) in our study. Cluster 1 showed greater biochemical severity at presentation, including higher median lactate (2.40 vs. 2.20 mmol L⁻¹; p < 0.001), serum creatinine (1.39 vs. 1.20 mg dL⁻¹; p < 0.001), blood urea nitrogen (28 vs. 25 mg dL⁻¹; p < 0.001), and neutrophil-to-lymphocyte ratio (11.12 vs. 10.38; p < 0.001), and a higher mean SOFA score (7.05 ± 3.85 vs. 6.76 ± 3.87; p < 0.001). Despite this, Cluster 1 required mechanical ventilation more frequently (46.1% vs. 42.2%; p < 0.001) and had a higher incidence of AKI (58.1% vs. 55.6%; p = 0.009), including more stage 3 AKI (17.2% vs. 15.2%; p < 0.001) and dialysis (6.6% vs. 5.2%; p = 0.005), yet experienced similar in-hospital mortality (15.4% vs. 15.8%; p = 0.615) and comparable ICU (2.18 vs. 2.26 days; p = 0.254) and hospital lengths of stay (6.63 vs. 6.80 days; p = 0.251). Conclusions: Two septic shock phenotypes were identified, one with marked early organ dysfunction (Cluster 1) and another with milder initial derangements (Cluster 2), yet both showed convergent short-term mortality and lengths of stay despite divergent support needs. These results challenge reliance on single-parameter severity markers and underscore the need for phenotype-guided risk stratification and personalized management strategies in septic shock.

Background: Cardiorenal syndrome (CRS) reflects bidirectional heart–kidney injury whose mechanisms extend far beyond hemodynamics. High-throughput genomics and multi-omics now illuminate the molecular circuits that couple cardiac and renal dysfunction. Methods: We narratively synthesize animal and human studies leveraging transcriptomics, proteomics, peptidomics, metabolomics, and non-coding RNA profiling to map convergent pathways in CRS and to highlight biomarker and therapeutic implications. Results: Across acute and chronic CRS models, omics consistently converge on extracellular matrix (ECM) remodeling and fibrosis (e.g., FN1, POSTN, collagens), immune–inflammatory activation (IL-6 axis, macrophage/complement signatures), renin–angiotensin–aldosterone system hyperactivity, oxidative stress, and metabolic/mitochondrial derangements in both organs. Single-nucleus and bulk transcriptomes reveal tubular dedifferentiation after cardiac arrest-induced AKI and myocardial reprogramming with early CKD, while quantitative renal proteomics in heart failure demonstrates marked upregulation of ACE/Ang II and pro-fibrotic matricellular proteins despite near-normal filtration. Human translational data corroborate these signals: urinary peptidomics detects CRS-specific collagen fragments and protease activity, and circulating FN1/POSTN and selected microRNAs (notably miR-21) show diagnostic potential. Epigenetic and microRNA networks appear to integrate these axes, nominating targets such as anti-miR-21 and anti-fibrotic strategies; pathway-directed repurposing exemplifies dual-organ benefit. Conclusions: Genomics and multi-omics recast CRS as a systems disease driven by intertwined fibrosis, inflammation, neurohormonal and metabolic programs. We propose a translational framework that advances (i) composite biomarker panels combining injury, fibrosis, and regulatory RNAs; (ii) precision, pathway-guided therapies; and (iii) integrated, longitudinal multi-omics of well-phenotyped CRS cohorts to enable prediction and personalized intervention.

Background: Melatonin has antioxidant and anti-inflammatory properties that may attenuate ischemia-reperfusion injury, but randomized cardiovascular trial data remain inconsistent. Objectives: This study sought to evaluate the association of melatonin supplementation with cardiovascular outcomes across randomized trials. Methods: We performed a systematic review and meta-analysis of randomized trials comparing melatonin with placebo, usual care, or no melatonin in patients with cardiovascular disease. PubMed, Embase, and CENTRAL were searched from inception to 1 January 2026. Random-effects models with Hartung–Knapp–Sidik–Jonkman confidence intervals were used. Prespecified outcomes included left ventricular ejection fraction (LVEF), change in LVEF, troponin, infarct size by cardiac magnetic resonance, heart failure outcomes, inflammatory and oxidative stress biomarkers, and adverse events. Results: A total of 14 randomized controlled trials involving 1027 participants were included. Melatonin significantly improved change in LVEF from baseline to follow-up (mean difference: 3.95 percentage points; 95% CI: 1.70–6.20; p < 0.001), with the most consistent signal in coronary artery bypass grafting studies (mean difference: 4.65 percentage points; 95% CI: 2.56–6.74). Final LVEF was numerically higher with melatonin but not statistically significant. Troponin reduction was not significant. Narrative synthesis suggested lower inflammatory and oxidative stress markers after coronary artery bypass grafting and improvement in heart failure symptoms and quality of life, whereas infarct size findings in ST-segment elevation myocardial infarction were mixed and timing-dependent. Conclusions: Melatonin was associated with improved LVEF change, particularly in coronary artery bypass grafting settings, but benefit was not consistently demonstrated across final LVEF, troponin, or infarct size outcomes.

Background: Cardiogenic shock is a heterogeneous syndrome in which systemic inflammation may contribute to cardiovascular risk and adverse outcomes beyond hemodynamic compromise alone. Methods: We conducted a retrospective multicenter cohort study using the eICU Collaborative Research Database (2014–2015) to identify inflammatory phenotypes among adults admitted to intensive care units with cardiogenic shock. Inflammatory indices derived from admission hematologic parameters (including NLR, PLR, MLR, NPAR, SII, SIRI, and AISI) were analyzed using principal component analysis, followed by hierarchical and k-means clustering to identify biologically distinct inflammatory phenotypes. Clinical characteristics and short-term outcomes were compared across clusters. Results: Among 419 patients, two phenotypes were identified. Cluster 1 (n = 52) was characterized by older age, a higher prevalence of chronic kidney disease (CKD), more advanced renal and hepatic dysfunction, along with a hyperinflammatory, lymphopenic profile. Cluster 2 (n = 367) exhibited comparatively lower inflammatory indices and less biochemical derangement. There was a significant difference in the prevalence of CKD, the need for mechanical ventilation, and history of malignancy between clusters. Despite clear biological separation, short-term clinical outcomes, including rates of acute kidney injury requiring renal replacement therapy, vasopressor use, hospital length of stay, and in-hospital mortality, were similar across clusters. Conclusions: These findings suggest that cardiogenic shock encompasses distinct inflammatory phenotypes, but inflammatory clustering based on routine admission laboratory data alone may have limited utility for short-term risk stratification.