Prevalence of amyloid blood clots in COVID-19 plasma

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

doi:10.1101/2020.07.28.20163543

Cited by 9 publications

(15 citation statements)

References 43 publications

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“…Interestingly our data indicates increased levels of nicotinamide in severity and nicotinuric acid in outcome. Increased levels of nicotinuric acid in urine have been previously reported as pathogenic markers in metabolic syndrome and cardiovascular disease (Huang et al, 2013), again consistent with the known cardiovascular effects of SARS-CoV-2 infection (Fox et al, 2020; Grobler et al, 2020; Leisman et al, 2020; Libby and Lüscher, 2020; Paranjpe et al, 2020; Pretorius et al, 2020; Zheng et al, 2020).…”

Section: Discussionsupporting

confidence: 67%

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Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome

Roberts

Muelas

Taylor

et al. 2020

Preprint

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The diagnosis of COVID-19 is normally based on the qualitative detection of viral nucleic acid sequences. Properties of the host response are not measured but are key in determining outcome. Although metabolic profiles are well suited to capture host state, existing metabolomics studies are either underpowered, measure only a restricted subset of metabolites (‘targeted metabolomics’), compare infected individuals against uninfected control cohorts that are not suitably matched, or do not provide a compact predictive model.We here provide a well-powered, untargeted metabolomics assessment of 120 COVID-19 patient samples acquired at hospital admission. The study aims to predict patient’s infection severity (i.e. mild or severe) and potential outcome (i.e. discharged or deceased).High resolution untargeted LC-MS/MS analysis was performed on patient serum using both positive and negative ionization. A subset of 20 intermediary metabolites predictive of severity or outcome were selected based on univariate statistical significance and a multiple predictor Bayesian logistic regression model. The predictors were selected for their relevant biological function and include cytosine (reflecting viral load), kynurenine (reflecting host inflammatory response), nicotinuric acid, and multiple short chain acylcarnitines (energy metabolism) among others.Currently, this approach predicts outcome and severity with a Monte Carlo cross validated area under the ROC curve of 0.792 (SD 0.09) and 0.793 (SD 0.08), respectively. Prognostic tests based on the markers discussed in this paper could allow improvement in the planning of COVID-19 patient treatment.

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Section: Discussionsupporting

confidence: 67%

“…Finally, when adjusted for all factors pseudouridine 95 % CI lost significance indicating correlation with more than one factor. Interestingly, growing evidence points toward complications in COVID-19 arising through a vasculopathy and coagulopathy elicited by the infection (Pretorius et al, 2020) and may be indicative of this process.…”

Section: Discussionmentioning

confidence: 99%

Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome

Roberts

Muelas

Taylor

et al. 2020

Preprint

Self Cite

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“…However, SARS-CoV-2 also secretes products/proteins that modulate blood clotting cascades (Eslamifar et al, 2020). Pretorius et al (2020aPretorius et al ( ,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: 99%

“…SARS-CoV-2 can also drive multi-organ injury via stimulation of clotting cascades ( Pretorius et al, 2020a ) and related thromboinflammation, dysregulation of the renin–angiotensin–aldosterone system, and endothelial cell damage ( Grobler et al, 2020 ; Gupta et al, 2020 ). Infection-mediated endothelial injury and endothelialitis (marked by the presence of activated macrophages and neutrophils) can trigger excessive thrombin production, inhibit fibrinolysis, and activate complement pathways in a manner that leads to microvascular dysfunction and microthrombi deposition.…”

Section: Acute Covid-19mentioning

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

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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.

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“…Neurological changes caused by COVID-19 show similarities with multiple sclerosis [181] and myositis is a manifestation of SARS-CoV-2 infection [139]. Amyloid microclots are found in the native plasma of COVID-19 [182] and in diabetic patients, serum amyloid A (SAA) level may be associated with the severity of COVID-19 [183]. Aphasia is found in COVID-19 patients who have developed encephalopathy or ischemic stroke [184, 185].…”

Section: Resultsmentioning

confidence: 99%

A novel multi-omics-based identification of symptoms, comorbid conditions, and possible long-term complications in COVID-19

Barh

Tiwari

Andrade

et al. 2020

Preprint

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Till date the comprehensive clinical pictures, comorbid conditions, and long-term complications of COVID-19 are not known. Recently using a multi-omics-based strategy, we have predicted the drugs for COVID-19 management with ∼70% accuracy. Here, using a similar multi-omics-based bioinformatics approach and three-ways of analysis, we identified the symptoms, comorbid conditions, and short, mid and possible long-term complications of COVID-19 with ∼90% precision. In our analysis (i) we identified 27 parent, 170 child, and 403 specific conditions associated with COVID-19. (ii) Among the specific conditions, 36 are viral and 53 short-term, 62 short to mid to long-term, 194 mid to long-term, and 57 are congenital conditions. (iii) At a cut off “count of occurrence” of 4, we found ∼ 90% of the enriched conditions are associated with COVID-19. (iv) Except the dry cough and loss of taste, all other COVID-19 associated mild and severe symptoms are enriched. (v) Cardiovascular, pulmonary, metabolic, musculoskeletal, neuropsychiatric, kidney, liver, and immune system disorders are found as top comorbid conditions. (vi) Specific diseases such as myocardial infarction, hypertension, COPD, lung injury, diabetes, cirrhosis, mood disorders, dementia, macular degeneration, chronic kidney disease, lupus, arthritis etc. along with several other diseases are also enriched as top candidates. (vii) Interestingly, many cancers and congenital disorders associated with COVID-19 severity are also identified. (viii) Arthritis, dermatomyositis, glioma, diabetes, psychiatric disorder, cardiovascular diseases having bidirectional relationship with COVID-19 are also found as top ranked conditions. Based on the accuracy (∼90%) of this analysis, long presence of SARS-CoV-2 RNA in human, and our previously proposed “genetic remittance” assumption, we hypothesize that all the identified comorbid conditions including the short-long-mid and mid-long non-communicable diseases (NCDs) could also be long-term consequences in COVID-19 survivors and warrants long-term observational studies.

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Prevalence of amyloid blood clots in COVID-19 plasma

Cited by 9 publications

References 43 publications

Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome

Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome

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

A novel multi-omics-based identification of symptoms, comorbid conditions, and possible long-term complications in COVID-19

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