Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 12

Published: June 23, 2021

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of disease 2019 (COVID-19). Across the globe, subset patients who sustain an SARS-CoV-2 infection are developing wide range persistent symptoms that do not resolve over course many months. These being given diagnosis Long COVID or Post-acute sequelae COVID-19 (PASC). It is likely individual with PASC have different underlying biological factors driving their symptoms, none which mutually exclusive. This paper details mechanisms by RNA viruses beyond just be connected to long-term health consequences. also reviews literature on and other virus-initiated chronic syndromes such as post-Ebola myalgic encephalomyelitis/chronic fatigue (ME/CFS) discuss scenarios for symptom development. Potential contributors include consequences from injury one multiple organs, reservoirs in certain tissues, re-activation neurotrophic pathogens herpesviruses under conditions immune dysregulation, interactions host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity primed cells, autoimmunity due molecular mimicry between pathogen proteins. individualized nature suggests therapeutic approaches may required best manage care specific diagnosis.

Language: Английский

---

Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin

Cardiovascular Diabetology, Journal Year: 2021, Volume and Issue: 20(1)

Published: Aug. 23, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of disease 2019 (COVID-19), is characterized by clinical pathologies, including various coagulopathies that may be accompanied hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from symptoms. This commonly termed Long COVID/Post-Acute Sequelae (PASC). Here we refer to it as COVID/PASC. Lingering symptoms persist for much 6 months (or longer) where survivors complain recurring fatigue or muscle weakness, being out breath, sleep difficulties, anxiety depression. Given blood clots can block microcapillaries thereby inhibit oxygen exchange, here investigate if lingering individuals with COVID/PASC manifest might due presence persistent circulating plasma microclots are resistant fibrinolysis.We use techniques proteomics fluorescence microscopy study samples healthy individuals, Type Diabetes Mellitus (T2DM), COVID-19, those symptoms.We show still contain large anomalous (amyloid) deposits (microclots). We also these both fibrinolysis (compared controls T2DM), even trypsinisation. After second trypsinization, pellet (microclots) were solubilized. detected inflammatory molecules substantially increased supernatant trapped solubilized COVID/PASC, versus equivalent volume fully digested fluid control T2DM. Of particular interest was substantial increase α(2)-antiplasmin (α2AP), fibrinogen chains, well Serum Amyloid A (SAA) fibrinolytic-resistant deposits.Clotting pathologies infection benefit following regime continued anticlotting therapy support fibrinolytic system function.

Language: Английский

---

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Biochemical Journal, Journal Year: 2022, Volume and Issue: 479(4), P. 537 - 559

Published: Feb. 23, 2022

Post-acute sequelae of COVID (PASC), usually referred to as ‘Long COVID’ (a phenotype COVID-19), is a relatively frequent consequence SARS-CoV-2 infection, in which symptoms such breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions the blood coagulation system) persist long after initial infection. It bears similarities other post-viral syndromes, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this separate disease entity, refer it under broad terminology ‘COVID’, although its demographics are quite different from those acute COVID-19. A few years ago, we discovered that fibrinogen can clot into an anomalous ‘amyloid’ form fibrin (like β-rich amyloids prions) resistant proteolysis (fibrinolysis). The result, strongly manifested platelet-poor plasma (PPP) individuals with Long COVID, extensive amyloid microclots persist, entrap proteins, may lead production various autoantibodies. These more-or-less easily measured PPP stain thioflavin T simple fluorescence microscope. Although multifarious, here argue ability these (fibrinaloids) block up capillaries, thus limit passage red cells hence O2 exchange, actually underpin majority symptoms. Consistent this, preliminary report, has been shown suitable closely monitored ‘triple’ anticoagulant therapy leads removal also removes Fibrin represent novel potentially important target for both understanding treatment related disorders.

Language: Английский

---

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

---

SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19

Bioscience Reports, Journal Year: 2021, Volume and Issue: 41(8)

Published: July 30, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One most important pathologies, hypercoagulation and microclots in lungs patients. Here we study effect isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis. Using scanning electron fluorescence microscopy well mass spectrometry, investigate this to interact with platelets fibrin(ogen) directly blood hypercoagulation. platelet-poor plasma (PPP), show that may interfere flow. Mass spectrometry also showed when added healthy PPP, it results structural changes β γ fibrin(ogen), complement 3, prothrombin. These proteins were substantially resistant trypsinization, presence S1. suggest that, part, circulation contribute COVID-19 positive patients substantial impairment fibrinolysis. Such lytic result persistent large have noted here previously samples This observation relevance treatment hypercoagulability

Language: Английский

---

Long COVID: pathophysiological factors and abnormalities of coagulation

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

---

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

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

---

COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences

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

---

Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(754)

Published: July 3, 2024

The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort 24 participants at time points ranging from 27 to 910 days acute using the radiopharmaceutical agent [

Language: Английский

---

Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte

Cardiovascular Diabetology, Journal Year: 2021, Volume and Issue: 20(1)

Published: May 7, 2021

Abstract Rationale About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact glycation ACE2 on by can be high importance. Objective To evaluate presence in cardiomyocytes from heart autopsy cases compared to Non-DM; investigate role SARS-COV-2 entry cardiomyocytes. Methods and results We evaluated consecutive cases, deceased for COVID-19, Italy between Apr 30, 2020 Jan 18, 2021. cardiomyocytes, expression (total glycosylated form), transmembrane protease serine protease-2 (TMPRSS2) protein. order study alterations, independently we investigated ACE2, TMPRSS2 proteins Non-DM explanted-hearts. Finally, effects protein modification, an vitro recombinant human (hACE2) was performed binding Spike authors included cardiac tissue 97 autopsies. diagnosed 37 (38%). Fourth-seven out autopsies (48%) had RNA Thirty (81%) 17 60 (28%) Total expressions were higher autopsied explanted hearts than Non-DM. exposure monomeric hACE2 120 mM glucose 12 days led non-enzymatic four lysine residues neck domain affecting oligomerization. Conclusions upregulation forms) along glycation, could increase susceptibility COVID-19 favouring cellular SARS-CoV2.

Language: Английский

---