Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19 DOI Creative Commons
Michael J. Peluso,

Dylan Ryder,

Robert R. Flavell

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 31, 2023

ABSTRACT The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in cohort 24 participants at time points ranging from 27 to 910 days acute using novel radiopharmaceutical agent, [ 18 F]F-AraG, highly selective tracer allows for anatomical quantitation activated T lymphocytes. Tracer uptake the COVID group, which included those with without Long symptoms, was significantly higher compared pre-pandemic controls many regions, including brain stem, spinal cord, bone marrow, nasopharyngeal hilar lymphoid tissue, cardiopulmonary tissues, gut wall. Although cell activation tended be imaged closer illness, increased up 2.5 years infection. observed cord wall associated presence symptoms. In addition, lung tissue persistent pulmonary Notably, these tissues also individuals COVID. Given high F]F-AraG detected gut, we obtained colorectal situ hybridization RNA immunohistochemical studies subset identified cellular rectosigmoid lamina propria all participants, 158 676 initial COVID-19 suggesting could long-term immunological perturbations.

Language: Английский

Long COVID: major findings, mechanisms and recommendations DOI Open Access
Hannah Davis, Lisa McCorkell, Julia Moore Vogel

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(3), P. 133 - 146

Published: Jan. 13, 2023

Language: Английский

Citations

2875
The neurobiology of long COVID DOI Creative Commons
Michelle Monje, Akiko Iwasaki

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

Citations

304
Long COVID: pathophysiological factors and abnormalities of coagulation DOI Creative Commons
Simone Turner, Asad Khan, David Putrino

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(6), P. 321 - 344

Published: April 19, 2023

Acute COVID-19 infection is followed by prolonged symptoms in approximately one ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host (chronic inflammation, metabolic endocrine dysregulation, immune autoimmunity); downstream impacts (tissue damage from the initial infection, tissue hypoxia, dysbiosis, autonomic nervous system dysfunction). These mechanisms culminate long-term persistence disorder characterized a thrombotic endothelialitis, endothelial hyperactivated platelets, fibrinaloid microclots. abnormalities blood vessels coagulation affect every organ represent unifying pathway for various

Language: Английский

Citations

154
Proteomics of fibrin amyloid microclots in long COVID/post-acute sequelae of COVID-19 (PASC) shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system DOI Creative Commons
Arneaux Kruger,

Maré Vlok,

Simone Turner

et al.

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Sept. 21, 2022

Post-acute sequelae of COVID-19 (PASC), also now known as long COVID, has become a major global health and economic burden. Previously, we provided evidence that there is significant insoluble fibrin amyloid microclot load in the circulation individuals with these microclots entrap substantial number inflammatory molecules, including those might prevent clot breakdown. Scientifically, most challenging aspect this debilitating condition traditional pathology tests such serum CRP (C-reactive protein) may not show any abnormal markers, albeit measure only soluble molecules. Elevated, or biomarkers IL-6, D-Dimer fibrinogen indicate an increased risk for thrombosis host immune response COVID-19. The absence standard tests, result amount confusion patients clinicians, are extremely sick even bed-ridden but no regular identifiable reason their disease. Biomarkers currently available cannot detect molecules present identified therefore unable to confirm presence mechanisms drive formation.

Language: Английский

Citations

120
A review of cytokine-based pathophysiology of Long COVID symptoms DOI Creative Commons

Russell N. Low,

Ryan Low, Athena Akrami

et al.

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

Published: March 31, 2023

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase illness, in whom recovery is prolonged, or new are developed over months. Here, we propose a description pathophysiology COVID presentation based on inflammatory cytokine cascades and p38 MAP kinase signaling pathways that regulate production. In this model, SARS-CoV-2 viral infection hypothesized to trigger dysregulated peripheral immune system activation subsequent release. Chronic low-grade inflammation leads brain microglia an exaggerated release central cytokines, producing neuroinflammation. Immunothrombosis linked chronic microclot formation decreased tissue perfusion ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS "brain fog," arthralgias, paresthesias, dysautonomia, GI ophthalmic problems can consequently arise as result elevated cytokines. There abundant similarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms viral-induced epigenetic changes gene expression may lead patients, predisposing some develop autoimmunity, which be gateway ME/CFS.

Language: Английский

Citations

107
COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences DOI Creative Commons
Felix Scholkmann,

Christian-Albrecht May

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 246, P. 154497 - 154497

Published: May 3, 2023

Worldwide there have been over 760 million confirmed coronavirus disease 2019 (COVID-19) cases, and 13 billion COVID-19 vaccine doses administered as of April 2023, according to the World Health Organization. An infection with severe acute respiratory syndrome 2 (SARS-CoV-2) can lead an disease, i.e. COVID-19, but also a post-acute (PACS, "long COVID"). Currently, side effects vaccines are increasingly being noted studied. Here, we summarise currently available indications discuss our conclusions that (i) these specific similarities differences PACS, (ii) new term should be used refer (post-COVID-19 vaccination syndrome, PCVS, colloquially "post-COVIDvac-syndrome"), (iii) is need distinguish between (ACVS) (PACVS) - in analogy PACS ("long Moreover, address mixed forms caused by natural SARS-CoV-2 vaccination. We explain why it important for medical diagnosis, care research use terms (PCVS, ACVS PACVS) order avoid confusion misinterpretation underlying causes enable optimal therapy. do not recommend "Post-Vac-Syndrome" imprecise. The article serves current problem "medical gaslighting" relation PCVS raising awareness among professionals supplying appropriate terminology disease.

Language: Английский

Citations

96
Why we need a deeper understanding of the pathophysiology of long COVID DOI
Akiko Iwasaki, David Putrino

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(4), P. 393 - 395

Published: Feb. 15, 2023

Language: Английский

Citations

88
The Hiking Optimization Algorithm: A novel human-based metaheuristic approach DOI Creative Commons
Sunday O. Oladejo, Stephen O. Ekwe, Seyedali Mirjalili

et al.

Knowledge-Based Systems, Journal Year: 2024, Volume and Issue: 296, P. 111880 - 111880

Published: May 3, 2024

In this paper, a novel metaheuristic called 'The Hiking Optimization Algorithm' (HOA) is proposed. HOA inspired by hiking, popular recreational activity, in recognition of the similarity between search landscapes optimization problems and mountainous terrains traversed hikers. HOA's mathematical model premised on Tobler's Function (THF), which determines walking velocity hikers (i.e. agents) considering elevation terrain distance covered. THF employed determining hikers' positions course solving an problem. performance demonstrated benchmarking with 29 well-known test functions (including unimodal, multimodal, fixed-dimension composite functions), three engineering design (EDPs), I-beam, tension/compression spring, gear train problems) two N-P Hard Traveling Salesman's Knapsack Problems). Moreover, results are verified comparison to 14 other metaheuristics, including Teaching Learning Based (TLBO), Genetic Algorithm (GA), Differential Evolution (DE), Particle Swarm Optimization, Grey Wolf Optimizer (GWO) as well newly introduced algorithms such Komodo Mlipir (KMA), Quadratic Interpolation (QIO), Coronavirus (COVIDOA). study, we employ statistical tests Wilcoxon rank sum, Friedman test, Dunn's post hoc for evaluation. competitive and, many instances, outperform aforementioned metaheuristics.

Language: Английский

Citations

66
Long COVID: a review and proposed visualization of the complexity of long COVID DOI Creative Commons
Rubeshan Perumal, Letitia Shunmugam, Kogieleum Naidoo

et al.

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

Published: April 20, 2023

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose visual description the complexity COVID its pathogenesis that can be used by researchers, clinicians, public health officials to guide global effort toward an improved understanding eventual mechanism-based provision care afflicted patients. The proposed visualization framework for should evidence-based, dynamic, modular, systems-level approach condition. Furthermore, further research such could establish strength relationships between pre-existing conditions (or risk factors), biological mechanisms, resulting clinical phenotypes outcomes COVID. Notwithstanding significant contribution disparities in access social determinants have on disease course long our model focuses primarily mechanisms. Accordingly, sets out scientific, clinical, efforts better understand abrogate burden imposed

Language: Английский

Citations

65
Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update DOI

Sizhen Su,

Yi‐Miao Zhao, Na Zeng

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(10), P. 4056 - 4069

Published: July 25, 2023

Language: Английский

Citations

65