Prevalence of readily detected amyloid blood clots in ‘unclotted’ Type 2 Diabetes Mellitus and COVID-19 plasma: A preliminary report

Pretorius, Etheresia; Venter, Chantelle; Laubscher, Gert Jacobus; Lourens, Petrus Johannes; Steenkamp, Janami; Kell, Douglas B.

doi:10.21203/rs.3.rs-64855/v2

Cited by 6 publications

(19 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously we have shown that naïve PPP (exposed to ThT) from healthy individuals and T2DM, have significantly less anomalous clotlets, compared to acute COVID-19 PPP (Pretorius et al, 2020). Here we show that PPP from Long COVID/PASC samples also have considerable anomalous (amyloid) clotlets, similar to that of acute COVID-19 PPP samples.…”

Section: Platelet Poor Plasma (Ppp): Amyloid Protein and Anomalous Clotting In Platelet Poor Plasma Samples Before And After Two Trypsin supporting

confidence: 63%

“…In the current study, we investigate if the lingering symptoms that individuals with Long COVID/PASC might be due to the presence of persistent circulating plasma clots that are resistant to fibrinolysis. We have previously shown that large anomalous (amyloid) fibrin(ogen) deposits are present in plasma from acute COVID-19 patients (Pretorius et al, 2020. Here we show that plasma samples from Long COVID/PASC still contain large anomalous (amyloid) deposits, and that these deposits are most resistant to fibrinolysis, even with the treatment of a two-step trypsin method.…”

Section: Introductionmentioning

confidence: 50%

“…Acute COVID-19 patients may suffer from thrombocytopenia that may lead to life-threatening disseminated intravascular coagulation (DIC) (Terpos et al, 2020). Predisposing risk factors or co-morbidities that may also lead to a poor prognosis of acute COVID-19, are cardiovascular disease, diabetes, arterial hypertension, obesity (Pretorius et al, 2020, Finer et al, 2020, Yates et al, 2020, Sattar et al, 2020, Gerotziafas et al, 2020, Li et al, 2020a, as well as cancer (Malek et al, 2020). Complications like liver injury, acute respiratory distress syndrome (ARDS), sepsis, myocardial injury, renal insufficiency and Multiple Organ Dysfunction Syndrome (MODS) are common in cancer patients with COVID-19 (Malek et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Pretorius

Vlok

Venter

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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

show abstract

Section: Platelet Poor Plasma (Ppp): Amyloid Protein and Anomalous Clotting In Platelet Poor Plasma Samples Before And After Two Trypsin supporting

confidence: 63%

Section: Introductionmentioning

confidence: 50%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Pretorius

Vlok

Venter

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, SARS-CoV-2 also secretes products/proteins that modulate blood clotting cascades ( Eslamifar et al, 2020 ). Pretorius et al (2020a , b , 2021) identified fibrinolytic resistant amyloid microclots in COVID-19 plasma ( Figure 4 ) and in plasma samples collected from 11 PASC subjects. This suggests that patients who suffer from both issues/insults might be disproportionally impacted by PASC symptoms that could result from blood inflammatory/coagulation cascades.…”

Section: Microbiome Dysbiosis Can Disrupt Host Metabolic and Neuroendocrine Signaling And/or Epithelial Barrier Functionmentioning

confidence: 98%

“…COVID-19 is associated with a profound escalation in clotting cascades ( Grobler et al, 2020 ) including an amyloid form of fibrin that may be associated with infection-related systemic inflammatory conditions ( Esposito et al, 2016 ; Pretorius et al, 2020b ). This may affect the meninges, the three membrane layers surrounding the central nervous system.…”

Section: Sars-cov-2 And/or Related Inflammatory Insults May Disrupt Brainstem Signalingmentioning

confidence: 99%

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

Proal¹,

2021

View full text Add to dashboard Cite

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

show abstract

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

Grobbelaar

Kruger

Venter

et al. 2022

Semin Thromb Hemost

Self Cite

View full text Add to dashboard Cite

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

show abstract

Prevalence of readily detected amyloid blood clots in ‘unclotted’ Type 2 Diabetes Mellitus and COVID-19 plasma: A preliminary report

Cited by 6 publications

References 43 publications

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

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

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

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

Contact Info

Product

Resources

About