Probing long COVID through a proteomic lens: a comprehensive two-year longitudinal cohort study of hospitalised survivors

EBioMedicine, Journal Year: 2023, Volume and Issue: 98, P. 104851 - 104851

Published: Nov. 3, 2023

As a debilitating condition that can impact whole spectrum of people and involve multi-organ systems, long COVID has aroused the most attention than ever. However, mechanisms are not clearly understood, underlying biomarkers affect long-term consequences COVID-19 paramount to be identified.

Language: Английский

---

COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 6, 2023

Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, an image threshold method, postmortem from nine critically ill COVID-19 patients age-matched cadavers healthy individuals. Differentially expressed proteins identified quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, infarction, as well mononuclear cells. Immunostaining activation both astrocytes, severe damage blood-brain barrier (BBB) various degrees perivascular infiltration predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes occasionally CD4+/CD8+ T lymphocytes. Quantitative assays combined bioinformatics analysis upregulated involved immune responses, autophagy cellular metabolism compared control brains. Proteins brain development, neuroprotection, extracellular matrix basement membrane downregulated, potentially caused transforming growth factor β receptor vascular endothelial signaling pathways. Thus, our results define histopathological molecular profiles COVID-19-associated monocytic encephalitis (CAME) suggest therapeutic targets.

Language: Английский

---

Mechanisms of SARS-CoV-2-associated anosmia

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2759 - 2766

Published: June 21, 2023

Anosmia, the loss of sense smell, is one main neurological manifestations COVID-19. Although SARS-CoV-2 virus targets nasal olfactory epithelium, current evidence suggests that neuronal infection extremely rare in both periphery and brain, prompting need for mechanistic models can explain widespread anosmia COVID-19 patients. Starting from work identifying non-neuronal cell types are infected by system, we review effects these supportive cells epithelium brain posit downstream mechanisms through which smell impaired We propose indirect contribute to altered system function COVID-19-associated anosmia, as opposed or neuroinvasion into brain. Such include tissue damage, inflammatory responses immune infiltration systemic circulation cytokines, downregulation odorant receptor genes sensory neurons response local signals. also highlight key unresolved questions raised recent findings.

Language: Английский

---

Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 11(8), P. 726 - 738

Published: July 17, 2023

Despite advances in the treatment and mitigation of critical illness caused by infection with SARS-CoV-2, millions survivors have a devastating, post-acute syndrome known as long COVID. A large proportion patients COVID nervous system dysfunction, which is also seen distinct but overlapping condition post-intensive care (PICS), putting COVID-19-related at high risk long-lasting morbidity affecting multiple organ systems and, result, engendering measurable deficits quality life productivity. In this Series paper, we discuss neurological, cognitive, psychiatric sequelae who survived due to COVID-19. We review current knowledge epidemiology pathophysiology persistent neuropsychological impairments, outline potential preventive strategies based on safe, evidence-based approaches management pain, agitation, delirium, anticoagulation, ventilator weaning during illness. highlight priorities for future research, including possible therapeutic approaches, offer considerations health services address escalating burden

Language: Английский

---

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

Nature Aging, Journal Year: 2023, Volume and Issue: 3(12), P. 1561 - 1575

Published: Nov. 13, 2023

Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) linked to severe neurological manifestations. Senescent cells contribute brain aging, but the impact of virus-induced senescence on neuropathologies unknown. Here we show that senescent accumulate in aged human organoids senolytics reduce age-related inflammation rejuvenate transcriptomic aging clocks. In postmortem brains patients with COVID-19 observed increased cell accumulation compared age-matched controls. Exposure acute respiratory syndrome 2 (SARS-CoV-2) induced cellular senescence, analysis revealed unique SARS-CoV-2 inflammatory signature. Senolytic treatment infected blocked viral replication prevented distinct neuronal populations. human-ACE2-overexpressing mice, improved clinical outcomes, promoted dopaminergic neuron survival alleviated proinflammatory gene expression. Collectively our results demonstrate an important role driving SARS-CoV-2-induced neuropathology, therapeutic benefit senolytic treatments.

Language: Английский

---