Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC)

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

Published: Aug. 6, 2022

Fibrin(ogen) amyloid microclots and platelet hyperactivation previously reported as a novel finding in South African patients with the coronavirus 2019 disease (COVID-19) Long COVID/Post-Acute Sequelae of COVID-19 (PASC), might form suitable set foci for clinical treatment symptoms COVID/PASC. A COVID/PASC Registry was subsequently established an online platform where can report previous comorbidities.

Language: Английский

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The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Biochemical Journal, Journal Year: 2022, Volume and Issue: 479(16), P. 1653 - 1708

Published: Aug. 31, 2022

Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety acute circumstances. We argue here that I-R injury also underpins elements pathology chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be fibrin amyloid microclot blockage capillaries, for instance as exercise started; reperfusion necessary corollary when it finishes. rehearse mechanistic evidence these occurrences here, terms their manifestation oxidative stress, hyperinflammation, mast cell activation, production marker metabolites related activities. Such microclot-based phenomena can explain both breathlessness/fatigue post-exertional malaise observed conditions, many other observables. The recognition processes implies, mechanistically, therapeutic benefit potentially to had from antioxidants, anti-inflammatories, iron chelators, suitable, safe fibrinolytics, and/or anti-clotting agents. review considerable existing consistent with this, biochemical mechanisms involved.

Language: Английский

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Relative Hypercoagulopathy of the SARS-CoV-2 Beta and Delta Variants when Compared to the Less Severe Omicron Variants Is Related to TEG Parameters, the Extent of Fibrin Amyloid Microclots, and the Severity of Clinical Illness

Seminars in Thrombosis and Hemostasis, Journal Year: 2022, Volume and Issue: 48(07), P. 858 - 868

Published: Sept. 29, 2022

Earlier variants of SARS-CoV-2 have been associated with hypercoagulability and an extensive formation fibrin amyloid microclots, which are considered to contribute the pathology coronavirus 2019 disease (COVID-19). The newer omicron appear be far more transmissible, but less virulent, even when taking immunity acquired from previous infections or vaccination into account. We here show that while clotting parameters significantly raised over those healthy, matched controls, they levels lower than seen severe such as beta delta. also observed individuals infected manifested microclot in platelet-poor plasma compared harboring virulent variants. measurement effects between different acts a kind "internal control" demonstrates relationship extent coagulopathies virulence variant interest. This adds evidence microclots may play important role reflecting severity symptoms COVID-19.

Language: Английский

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Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

Cells, Journal Year: 2023, Volume and Issue: 12(2), P. 262 - 262

Published: Jan. 9, 2023

The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is most common site of infection, a significant number reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although mechanisms pathogenesis are still being examined, viral components isolated from stool samples infected patients suggest potential fecal–oral transmission route. In addition, RNA has been detected in blood patients, making hematologic dissemination virus proposed route for Angiotensin-converting enzyme 2 (ACE2) receptors serve as cellular entry mechanism virus, these particularly abundant throughout tract, intestine, liver, pancreas extrapulmonary sites infection reservoirs developing mutations new variants that contribute to uncontrolled disease resistance treatments. This dysregulation immune play role profound inflammatory coagulative cascades increased severity risk death several COVID-19 patients. article reviews various gastrointestinal, pancreatic injury.

Language: Английский

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SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock

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

Published: Feb. 27, 2023

Irrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter critically ill patients in shock. Intensivists and traumatologists have embraced concept SHock-INduced Endotheliopathy (SHINE) as a foundational derangement progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends micro-thrombosis, enacting cycle worsening perfusion increasing catecholamines, injury, de-endothelialization, multiple organ failure. hypocoagulable/hyperfibrinolytic phenotype is thought be driven by release anti-thrombogenic mediators bloodstream perivascular sympathetic nerve tissue plasminogen activator directly into microvasculature. In state, this counterbalancing, yet maladaptive, attempt restore blood flow against systemically increased viscosity. We therefore review physiology with emphasis on glycocalyx function, unique biomarkers, coagulofibrinolytic mediators, setting stage understanding pathophysiology phenotypes SHINE various etiologies propose that exemplified whether related trauma-induced coagulopathy, sepsis-induced or post-cardiac arrest syndrome-associated coagulopathy. Regardless initial insult, appears catecholamine-driven entity which early disease course manifest hyper- hypocoagulopathic hypofibrinolytic imbalance. Moreover, these derangements rapidly evolve along thrombohemorrhagic spectrum depending etiology, timing, methods resuscitation. Given intricate hemochemical makeup changes during states, macroscopic whole tests coagulative kinetics clot strength serve clinically useful simple means hemostasis phenotyping. suggest viscoelastic assays such thromboelastography (TEG) rotational thromboelastometry (ROTEM) are currently most applicable clinical tools assaying global function—including fibrinolysis—to enable dynamic resuscitation products adjuncts those thrombotic hemorrhagic complications states.

Language: Английский

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Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases?

Biochemical Journal, Journal Year: 2023, Volume and Issue: 480(15), P. 1217 - 1240

Published: Aug. 16, 2023

It is now well established that the blood-clotting protein fibrinogen can polymerise into an anomalous form of fibrin amyloid in character; resultant clots and microclots entrap many other molecules, stain with fluorogenic stains, are rather resistant to fibrinolysis, block up microcapillaries, implicated a variety diseases including Long COVID, have been referred as fibrinaloids. A necessary corollary this polymerisation generation novel epitopes proteins would normally be seen ‘self’, otherwise immunologically silent. The precise conformation resulting fibrinaloid (that, prions classical proteins, adopt multiple, stable conformations) must depend on existing small molecules metal ions may (and some cases known to) bound before polymerisation. Any such epitopes, however, likely lead autoantibodies. convergent phenomenology, distinct conformations seeding for initiation propagation, emerging link knowledge prions, prionoids, amyloids We here summarise evidence above reasoning, which has substantial implications our understanding genesis autoimmunity possible prevention thereof) based primary process formation.

Language: Английский

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Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: July 16, 2024

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition that characterized by unresolved fatigue, post-exertion symptom exacerbation (PESE), cognitive dysfunction, orthostatic intolerance, and other symptoms. ME/CFS lacks established clinical biomarkers requires further elucidation of disease mechanisms. A growing number studies demonstrate signs hematological cardiovascular pathology in cohorts, including hyperactivated platelets, endothelial vascular dysregulation, anomalous clotting processes. To build on these findings, to identify potential can be related pathophysiology, we measured differences protein expression platelet-poor plasma (PPP) samples from 15 study participants 10 controls not previously infected with SARS-CoV-2, using DIA LC-MS/MS. We identified 24 proteins are significantly increased the group compared controls, 21 downregulated. Proteins processes - thrombospondin-1 (important platelet activation), factor 4, S were differentially expressed group, suggestive dysregulated coagulation system abnormal function. Complement machinery was also downregulated, C9 which forms part membrane attack complex. Additionally, significant upregulation lactotransferrin, S100-A9, an immunoglobulin variant. The findings this experiment implicate immune ME/CFS, bring attention or imposed endothelium. This highlights systems require research regards their contribution pathogenesis manifestation, biomarker potential, gives insight into risk for individuals affected diabetes mellitus.

Language: Английский

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Impact of COVID-19 on Thrombotic Complications in Microsurgery: Deep Inferior Epigastric Perforator Flap Outcomes Amid Pandemic

Plastic & Reconstructive Surgery Global Open, Journal Year: 2025, Volume and Issue: 13(2), P. e6544 - e6544

Published: Feb. 1, 2025

Background: Emerging research underscores the heightened risk of vasculitis and microvascular thrombosis in COVID-19 patients, alongside concerns about prothrombotic events post–severe acute respiratory syndrome coronavirus 2 vaccination. Following pandemic’s end, we sought a comprehensive analysis to elucidate its impact on microsurgical rates, informed by empirical anecdotal evidence. Methods: An institutional review board–approved retrospective analyzed autologous breast reconstruction cases women from January 2019 March 2022. Data patient history, infection, vaccination status, postoperative complications were collected. Patients categorized as prepandemic pandemic, based influence (infection or vaccination) for statistical evaluation. Results: Among 527 216 underwent surgery 311 during revealing thrombotic event rates 3.2% 5.4%, respectively. Further comparative showed no significant difference among patients affected through infection pandemic. Conclusions: Contrary concerns, status does not significantly increase deep inferior epigastric perforator flap reconstructions. This study offers vital insights, affirming safety efficacy procedures amid thereby guiding microsurgeons optimizing care post–COVID-19 era.

Language: Английский

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COVID-19 infection is a significant risk factor for death in patients presenting with acute cholecystitis: a secondary analysis of the ChoCO-W cohort study

World Journal of Emergency Surgery, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 25, 2025

During the coronavirus disease (COVID-19) pandemic, there has been a surge in cases of acute cholecystitis. The ChoCO-W global prospective study reported higher incidence gangrenous cholecystitis and adverse outcomes COVID-19 patients. Through this secondary analysis data, we aim to identify significant risk factors for mortality patients with during emphasizing role infection patient treatment efficacy." data from 2546 collected at 218 centers 42 countries admitted October 1, 2020, 31, 2021. Sixty-four them died. Nonparametric statistical univariate was performed compare who died survived. Significant were then entered into logistic regression model define predicting mortality. independent that predicted death (p < 0.001), postoperative complications type (open/laparoscopic) surgical intervention = 0.003). odds increased 5 times infection, 6 presence complications, it reduced by 86% adequate source control. Survivors predominantly underwent urgent laparoscopic cholecystectomy (52.3% vs. 23.4%). an factor Early emerged as cornerstone hemodynamically stable

Language: Английский

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Perioperative Diagnostik und Management von Hyperkoagulabilität und Thrombophilie in der Mikrochirurgie – Konsensus-Bericht der Deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie (DAM)

Handchirurgie · Mikrochirurgie · Plastische Chirurgie, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Zusammenfassung Der regelrechte Blutfluss durch mikrochirurgisch anastomosierte Gefäße ist für den Therapieerfolg der rekonstruktiven Mikrochirurgie post operationem entscheidend. Im Gegensatz zu inzwischen in weiten Teilen ausgereiften und standardisierten Anastomosentechniken steht die erfolgsentscheidende Partnerdisziplin evidenzbasierten mikrochirurgischen Hämostaseologie Hämorheologie allerdings noch am Anfang. Prospektive klinische Studien daraus ableitbare evidenzbasierte Empfehlungen fehlen. Lediglich standortspezifische Erfahrungswerte bilden heutzutage Grundlage des perioperativen Managements Mikrochirurgie. Gemeinsames Ziel dieser mannigfaltigen Bemühungen sind präoperative Identifikation erhöhter Gerinnungsneigungen (Hyperkoagulabilität) oder Gerinnungsaktivitäten (Thrombophilie) Formulierung korrespondierender Antikoagulationsregime. Zuge 43. Jahrestagung Deutschsprachigen Arbeitsgemeinschaft (DAM) im November 2022 Frankfurt wurden Grundlagen Gerinnung Physiologie von Experten Mikrochirurgie, Anästhesie diskutiert, sowie zusammen mit einem Literaturüberblick Konsensusempfehlungen das perioperative Management Hyperkoagulopathien erarbeitet. Anschluss Gremium Vorgehensweisen evaluiert, Entscheidungskriterien erfragt schließlich ein Empfehlungskonsens DAM bzgl. eines Algorithmus erarbeitet, diesem Positionspapier festgehalten ist.

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