The neurobiology of long COVID

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3484 - 3496

Published: Oct. 7, 2022

Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 represent major component the post-acute syndrome, also known as long COVID. Here, we review what is understood about pathobiology impact on CNS discuss possible neurobiological underpinnings cognitive affecting survivors. We propose chief mechanisms that may contribute to this emerging health crisis.

Language: Английский

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The immunology of long COVID

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(10), P. 618 - 634

Published: July 11, 2023

Language: Английский

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Molecular and spatial signatures of mouse brain aging at single-cell resolution

Cell, Journal Year: 2022, Volume and Issue: 186(1), P. 194 - 208.e18

Published: Dec. 28, 2022

The diversity and complex organization of cells in the brain have hindered systematic characterization age-related changes its cellular molecular architecture, limiting our ability to understand mechanisms underlying functional decline during aging. Here, we generated a high-resolution cell atlas aging within frontal cortex striatum using spatially resolved single-cell transcriptomics quantified gene expression spatial major types these regions over mouse lifespan. We observed substantially more pronounced state, expression, non-neuronal neurons. Our data revealed signatures glial immune activation aging, particularly enriched subcortical white matter, identified both similarities notable differences cell-activation patterns induced by systemic inflammatory challenge. These results provide critical insights into inflammation brain.

Language: Английский

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Serotonin reduction in post-acute sequelae of viral infection

Cell, Journal Year: 2023, Volume and Issue: 186(22), P. 4851 - 4867.e20

Published: Oct. 1, 2023

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses formulated explain the etiology PASC, including viral persistence, chronic inflammation, hypercoagulability, autonomic dysfunction. Here, we propose mechanism that links all four in single pathway provides actionable insights for therapeutic interventions. We find PASC are associated with serotonin reduction. Viral infection type I interferon-driven inflammation reduce through three mechanisms: diminished intestinal absorption precursor tryptophan; platelet hyperactivation thrombocytopenia, which impacts storage; enhanced MAO-mediated turnover. Peripheral reduction, turn, impedes activity vagus nerve thereby impairs hippocampal responses memory. These findings provide possible explanation neurocognitive symptoms persistence Long COVID, may extend other post-viral syndromes.

Language: Английский

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Distinguishing features of Long COVID identified through immune profiling

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 10, 2022

SARS-CoV-2 infection can result in the development of a constellation persistent sequelae following acute disease called post-acute COVID-19 (PASC) or Long COVID 1-3 . Individuals diagnosed with frequently report unremitting fatigue, post-exertional malaise, and variety cognitive autonomic dysfunctions ; however, basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping conjunction machine learning methods identify key immunological features distinguishing COVID. Marked differences noted specific circulating myeloid lymphocyte populations relative matched control groups, as well evidence elevated humoral responses directed against among participants Further, unexpected increases observed antibody non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis mediators various hormones also revealed pronounced differences, levels cortisol being uniformly lower groups. Integration data into unbiased models identified significant critical accurate classification COVID, decreased most individual predictor. These findings will help guide additional studies pathobiology may aid future objective biomarkers

Language: Английский

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ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: June 2, 2023

Some patients remain unwell for months after "recovering" from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance other symptoms that greatly interfere with their ability to function can leave some people housebound disabled. The illness (Long COVID) is similar myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well persisting illnesses follow a wide variety of infectious agents following major traumatic injury. Together, these are projected cost the U.S. trillions dollars. In this review, we first compare ME/CFS Long COVID, noting considerable similarities few differences. We then in extensive detail underlying pathophysiology two conditions, focusing on abnormalities central autonomic nervous system, lungs, heart, vasculature, immune gut microbiome, energy metabolism redox balance. This comparison highlights how strong evidence each abnormality, illness, helps set priorities future investigation. review provides current road map literature biology both illnesses.

Language: Английский

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Innate immune evasion strategies of SARS-CoV-2

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 11, 2023

Language: Английский

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Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 22, 2023

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, cognitive dysfunction that last for months impact everyday functioning, is referred to Long COVID under the general category post-acute sequelae SARS-CoV-2 infection (PASC). PASC highly heterogenous may be associated multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular neuropsychiatric disorders, pulmonary damage, renal failure, stroke, vascular endothelial dysregulation. A better understanding pathophysiologic mechanisms underlying essential guide prevention treatment. This review addresses potential hypotheses connect long-term health consequences. Comparisons between other virus-initiated chronic syndromes myalgic encephalomyelitis/chronic fatigue syndrome postural orthostatic tachycardia will addressed. Aligning identifying potentially regulated common underlining pathways necessary true nature PASC. The discussed contributors include from injury one or more organs, reservoirs replicating virus its remnants in several tissues, re-activation latent pathogens Epstein-Barr herpes viruses COVID-19 immune-dysregulated environment, interactions host microbiome/virome communities, clotting/coagulation dysfunctional brainstem/vagus nerve signaling, dysautonomia autonomic dysfunction, ongoing activity primed immune cells, autoimmunity due molecular mimicry pathogen proteins. individualized suggests different therapeutic approaches required best manage specific patients.

Language: Английский

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Long COVID science, research and policy

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(8), P. 2148 - 2164

Published: Aug. 1, 2024

Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system be severely disabling. The cumulative global incidence long around 400 million individuals, which estimated to have an annual economic impact approximately $1 trillion-equivalent about 1% economy. Several mechanistic pathways are implicated in COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement endothelial inflammation microbiome dysbiosis. devastating impacts on individual lives and, due its complexity prevalence, also has major ramifications for systems economies, even threatening progress toward achieving Sustainable Development Goals. Addressing challenge requires ambitious coordinated-but so far absent-global research policy response strategy. In this interdisciplinary review, we provide synthesis state scientific evidence assess human health, systems, economy metrics, forward-looking roadmap.

Language: Английский

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Long Covid: where we stand and challenges ahead

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 7, 2022

Abstract Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially Long Covid, has been defined a constellation signs symptoms which persist for weeks or months after the initial infection. PASC affects wide range diverse organs systems, with manifestations involving lungs, brain, cardiovascular system other such kidney neuromuscular system. The pathogenesis is complex multifactorial. Evidence suggests that seeding persistence in different organs, reactivation, response to unrelated viruses EBV, autoimmunity, uncontrolled inflammation are major drivers PASC. relative importance pathogenetic pathways may differ tissue organ contexts. vaccination, addition protecting against disease, reduces breakthrough infection although its actual impact remains be defined. represents formidable challenge health care systems dissecting mechanisms pave way targeted preventive therapeutic approaches.

Language: Английский

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