Tag: hypercoagulability

Post-translational modifications within fibrinaloid microclot complexes distinguish Pre-COVID-19 Postural Orthostatic Tachycardia Syndrome, Long COVID, and Long COVID-POTS and reveal disease-specific molecular pathways

Abstract:

Background: Pre-COVID-19 Postural orthostatic tachycardia syndrome (PC-POTS), Long COVID, and their overlap (LC-POTS) are chronic post-viral conditions marked by debilitating symptoms despite frequently normal routine laboratory results. We have previously identified insoluble fibrinaloid microclot complexes (FMCs) in Long COVID. It is not known whether FMCs are also present in PC-POTS, or whether post-translational modifications (PTMs) within FMC-entrapped proteins contribute to disease mechanisms.

Methods: Platelet-poor plasma from healthy controls, PC-POTS patients (collected prior to the COVID-19 pandemic), Long COVID (without POTS) and LC-POTS patients underwent fluorescence imaging flow cytometry to quantify FMCs. Proteomic analyses were performed on insoluble protein fractions using a double trypsin digestion strategy and data-independent liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential protein abundance, PTMs, and amyloidogenicity were compared across groups.

Results: Measured with imaging flow cytometry in objects/mL, higher levels of FMCs were present in disease groups compared to controls, although not statistically significant. Statistically significant differences potentially lay within FMC sizes and composition. Furthermore, despite only a few dysregulated proteins, FMC proteomics revealed extensive and disease-specific peptides with PTM dysregulation across coagulation, immune, and metabolic pathways. Long COVID displayed FMCs with PTMs of coagulation proteins including prominent advanced glycation end-products (AGE)- and oxidation-based modifications of fibrinogen subunits, particularly fibrinogen subunit A (FIBA), resembling diabetic glycation profiles. FMCs in PC-POTS showed fewer fibrinogen PTMs but markedly increased modifications in metabolic proteins, including oxidised apoA1 and apoB, and immune patterns with complement-related proteins (C3, C4A/B, IC1), immunoglobulin G1 (IGG1) and alpha 2 macroglobulin (A2MG). LC-POTS shared coagulation pathology with Long COVID and immune pathology with PC-POTS. Many dysregulated peptides were determined by in silco methods to be highly amyloidogenic, consistent with FMCs as beta-sheet-rich aggregates. Protein-level differences were minimal compared with PTM changes.

Conclusions: This study provides the first evidence that post-translational modifications (PTMs) within fibrinaloid microclots complexes (FMCs) uniquely distinguish pre-COVID-19 POTS, Long COVID, and Long COVID-POTS. Because PC-POTS samples were collected before SARS-CoV-2, their PTM patterns reflect intrinsic disease biology, allowing a clear separation from Long COVID-related changes. PTM profiling revealed pro-coagulant fibrinogen modifications in Long COVID and LC-POTS, metabolic-oxidative disruptions in Long COVID and PC-POTS, and immune dysregulation in PC-POTS and LC-POTS. None of these is detectable with routine assays, and all are independent of protein abundance. The consistent presence of amyloidogenic peptides suggests a contribution to microvascular dysfunction. These findings define disease-specific PTM landscapes and support new diagnostic and therapeutic avenues across autonomic and post-viral disorders.

Source: Renata Madre Booyens, Mare Vlok, Cecile Bester, Rashmin Hira, M Asad Khan, Douglas B Kell, Satish R Raj, Etheresia Pretorius. Post-translational modifications within fibrinaloid microclot complexes distinguish Pre-COVID-19 Postural Orthostatic Tachycardia Syndrome, Long COVID, and Long COVID-POTS and reveal disease-specific molecular pathways.
bioRxiv 2025.12.29.696828; doi: https://doi.org/10.64898/2025.12.29.696828 https://www.biorxiv.org/content/10.64898/2025.12.29.696828v1 (Full text available as PDF file)

A Comparative Study of the Coagulation Systems and Inflammatory Profiles of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Patients with Long COVID

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is a chronic condition that severely debilitates patients, yet it remains largely unfamiliar to many. Faced with scepticism as a real clinical entity for decades, the recognition of ME/CFS has improved with the emergence of Long COVID. This chronic illness manifests after an acute COVID-19 infection. With two-thirds of ME/CFS cases reported to be post-viral, a clear overlap emerges with Long COVID, as both conditions arise following an infectious illness.
The parallels between post-infectious ME/CFS and Long COVID are striking, with similarities in both symptomology and pathophysiology. One overlapping mechanism in both conditions, systemic inflammation, may be perpetuated by pathogen persistence or reactivation. While inflammation alone may not be accountable for the symptoms experienced in both conditions, it can lead to disruption in other physiological mechanisms. Owing to a bi-directional link with inflammation, coagulopathy and vascular changes may be exhibited in ME/CFS and Long COVID. Given the accessibility of blood samples, it is imperative to explore these mechanisms to uncover potential biomarkers for these conditions, both of which currently lack standardised diagnostic biomarkers.
A total of 83 participants were included in the study. The control group consisted of 19 healthy controls and 10 inflammatory controls (individuals with known inflammatory conditions), used to assess inflammation in a step-increase manner. The post-infectious group included 54 individuals, subdivided into 20 ME/CFS patients and 34 Long COVID patients. Statistical analyses were performed using GraphPad Prism 10 and R-Studio, with comparisons made using parametric or non-parametric tests, depending on data distribution. Significant results were considered at P<0.05. Multiple regression analyses were conducted to control for the effects of age and sex on the outcomes.
The techniques utilised in this dissertation focused on Virchow’s triad, a model explaining that hypercoagulability, stasis, and endothelial damage contribute to the aetiology and risk of thrombosis, particularly deep vein thrombosis. Framing the dissertation around this model offered a valuable framework to investigate potential pathological mechanisms and identify relevant biomarkers for these conditions. Common viscoelastic point-of-care devices, including TEG and ClotPro, were employed to examine the hypercoagulability component of Virchow’s triad.
These techniques demonstrated how standard laboratory tests are inefficient in revealing pathological alterations in Long COVID and ME/CFS, and how the insignificance of these results has prompted researchers and healthcare professionals to question the validity of these conditions. Despite this, newly developed fluorescent microscopy techniques revealed an increased presence of plasma structures resistant to fibrinolysis in the post-infectious groups, providing evidence of coagulopathy. This technique effectively distinguished the two conditions, with the Long COVID group showing a 2.75-fold increase in these plasma structures compared to the ME/CFS group. Additionally, the post-infectious groups displayed a marked presence of hyperactivated platelets and megakaryocytes in circulation, with platelet activation and aggregation being 1.35-fold higher in the Long COVID group compared to the ME/CFS group.
However, such microscopy techniques are low-throughput and labour-intensive, making them less practical for diagnostic purposes. An innovative high-throughput diagnostic technique known as real-time deformability cytometry was employed to investigate the second component of Virchow’s triad: alterations in blood rheology.
When isolating anomalous events and large clots in whole blood using the combined filter technique, the Long COVID group showed a 1.30-fold decrease in deformation compared to the ME/CFS group, indicating greater rigidity of these structures. Additionally, the ME/CFS group had a 1.31-fold decrease in the volume of these clots compared to the Long COVID group. Although significant differences were observed in both conditions and likely impact blood rheology, this technique requires further standardisation due to its novelty.
Lastly, endothelial biomarkers previously studied in other inflammatory diseases were investigated to better understand the extent of endothelial damage, the final aspect of Virchow’s triad. The flow luminescence immunoassay revealed a 1.29-fold reduction in cadherin-5 levels in the ME/CFS group compared to healthy controls. No significant differences were found in other endothelial biomarkers between the post-infectious groups, suggesting these biomarkers cannot be repurposed for these conditions.
Furthermore, the lack of replicability in endothelial analyte concentrations among different studies raises concerns about the reproducibility of this technique. When the findings of this dissertation are considered collectively through biomarker stratification, it becomes clear that distinct subgroups may exist within the studied populations. This highlights the importance of a multiparameter approach for diagnosis, although these novel investigations require further validation and should be replicated with larger sample sizes.
Through an examination of these mechanisms, this dissertation illustrated some commonalities between these diseases and demonstrated how Virchow’s triad may be implicated to some extent in both conditions. However, key differences were also identified between the conditions, highlighting the unique challenges each presents. As we investigate whether Long COVID signals the early onset of ME/CFS and consider whether insights gained from decades of combating ME/CFS can enlighten our understanding of Long COVID, we progress toward a deeper understanding of post-infectious conditions and the creative solutions required to address them.
Source: Arron, H. E. 2025. A Comparative Study of the Coagulation Systems and Inflammatory Profiles of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Patients with Long COVID. Unpublished doctoral thesis. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/1a98fb4e-a91f-497b-892e-716a25ee5358

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

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition that is characterized by unresolved fatigue, post-exertion symptom exacerbation (PESE), cognitive dysfunction, orthostatic intolerance, and other symptoms. ME/CFS lacks established clinical biomarkers and requires further elucidation of disease mechanisms.

A growing number of studies demonstrate signs of hematological and cardiovascular pathology in ME/CFS cohorts, including hyperactivated platelets, endothelial dysfunction, vascular dysregulation, and anomalous clotting processes. To build on these findings, and to identify potential biomarkers that can be related to pathophysiology, we measured differences in protein expression in platelet-poor plasma (PPP) samples from 15 ME/CFS study participants and 10 controls not previously infected with SARS-CoV-2, using DIA LC-MS/MS.

We identified 24 proteins that are significantly increased in the ME/CFS group compared to the controls, and 21 proteins that are significantly downregulated. Proteins related to clotting processes – thrombospondin-1 (important in platelet activation), platelet factor 4, and protein S – were differentially expressed in the ME/CFS group, suggestive of a dysregulated coagulation system and abnormal endothelial function. Complement machinery was also significantly downregulated, including C9 which forms part of the membrane attack complex. Additionally, we identified a significant upregulation of lactotransferrin, protein S100-A9, and an immunoglobulin variant.

The findings from this experiment further implicate the coagulation and immune system in ME/CFS, and bring to attention the pathology of or imposed on the endothelium. This study highlights potential systems and proteins that require further research with regards to their contribution to the pathogenesis of ME/CFS, symptom manifestation, and biomarker potential, and also gives insight into the hematological and cardiovascular risk for ME/CFS individuals affected by diabetes mellitus.

Source: Nunes, M., Vlok, M., Proal, A. et al. Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery. Cardiovasc Diabetol 23, 254 (2024). https://doi.org/10.1186/s12933-024-02315-x https://cardiab.biomedcentral.com/articles/10.1186/s12933-024-02315-x (Full text)

What Role Does Microthrombosis Play in Long COVID?

Abstract:

Soon after the outbreak of coronavirus disease 2019 (COVID-19), unexplained sustained fatigue, cognitive disturbance, and muscle ache/weakness were reported in patients who had recovered from acute COVID-19 infection. This abnormal condition has been recognized as “long COVID (postacute sequelae of COVID-19 [PASC])” with a prevalence estimated to be from 10 to 20% of convalescent patients. Although the pathophysiology of PASC has been studied, the exact mechanism remains obscure.

Microclots in circulation can represent one of the possible causes of PASC. Although hypercoagulability and thrombosis are critical mechanisms of acute COVID-19, recent studies have reported that thromboinflammation continues in some patients, even after the virus has cleared. Viral spike proteins and RNA can be detected months after patients have recovered, findings that may be responsible for persistent thromboinflammation and the development of microclots. Despite this theory, long-term results of anticoagulation, antiplatelet therapy, and vascular endothelial protection are inconsistent, and could not always show beneficial treatment effects.

In summary, PASC reflects a heterogeneous condition, and microclots cannot explain all the presenting symptoms. After clarification of the pathomechanisms of each symptom, a symptom- or biomarker-based stratified approach should be considered for future studies.

Source: Iba T, Connors JM, Levy JH. What Role Does Microthrombosis Play in Long COVID? Semin Thromb Hemost. 2023 Sep 25. doi: 10.1055/s-0043-1774795. Epub ahead of print. PMID: 37748518. https://pubmed.ncbi.nlm.nih.gov/37748518/

Persistent immune and clotting dysfunction detected in saliva and blood plasma after COVID-19

Abstract:

A growing number of studies indicate that coronavirus disease 2019 (COVID-19) is associated with inflammatory sequelae, but molecular signatures governing the normal versus pathologic convalescence process have not been well-delineated. Here, we characterized global immune and proteome responses in matched plasma and saliva samples obtained from COVID-19 patients collected between 20 and 90 days after initial clinical symptoms resolved.

Convalescent subjects showed robust total IgA and IgG responses and positive antibody correlations in saliva and plasma samples. Shotgun proteomics revealed persistent inflammatory patterns in convalescent samples including dysfunction of salivary innate immune cells, such as neutrophil markers (e.g., myeloperoxidase), and clotting factors in plasma (e.g., fibrinogen), with positive correlations to acute COVID-19 disease severity. Saliva samples were characterized by higher concentrations of IgA, and proteomics showed altered myeloid-derived pathways that correlated positively with SARS-CoV-2 IgA levels.

Beyond plasma, our study positions saliva as a viable fluid to monitor normal and aberrant immune responses including vascular, inflammatory, and coagulation-related sequelae.

Source: Jang H, Choudhury S, Yu Y, Sievers BL, Gelbart T, Singh H, Rawlings SA, Proal A, Tan GS, Qian Y, Smith D, Freire M. Persistent immune and clotting dysfunction detected in saliva and blood plasma after COVID-19. Heliyon. 2023 Jul 4;9(7):e17958. doi: 10.1016/j.heliyon.2023.e17958. PMID: 37483779; PMCID: PMC10362241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362241/ (Full text)

Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors

Abstract:

In general, an individual who experiences the symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2 infection is declared as recovered after 2 weeks. However, approximately 10–20% of these survivors have been reported to encounter long-term health problems, defined as ‘long COVID-19’, e.g., blood coagulation which leads to stroke with an estimated incidence of 3%, and pulmonary embolism with 5% incidence.
At the time of infection, the immune response produces pro-inflammatory cytokines that stimulate stromal cells to produce pro-hepatocyte growth factor (pro-HGF) and eventually is activated into hepatocyte growth factor (HGF), which helps the coagulation process in endothelial and epithelial cells. HGF is a marker that appears as an inflammatory response that leads to coagulation.
Currently, there is no information on the effect of SARS-CoV-2 infection on serum HGF concentrations as a marker of the prognosis of coagulation in long COVID-19 survivors. This review discusses the pathophysiology between COVID-19 and HGF, IL-6, and D-dimer.
Source: Zaira B, Yulianti T, Levita J. Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors. Current Issues in Molecular Biology. 2023; 45(7):5725-5740. https://doi.org/10.3390/cimb45070361 https://www.mdpi.com/1467-3045/45/7/361 (Full text)

The immunology of long COVID

Abstract:

Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge.

Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing–remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities.

Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein–Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways.

Source: Altmann, D.M., Whettlock, E.M., Liu, S. et al. The immunology of long COVID. Nat Rev Immunol (2023). https://doi.org/10.1038/s41577-023-00904-7 https://www.nature.com/articles/s41577-023-00904-7 (Full text)

Physiological underpinnings of long COVID: what have we learned?

In a review, Batta et al 2 , addressed the cardiovascular symptoms in COVID-19 patients with a focus on vascular dysfunction, arrhythmias, myocardial ischemia, and discussed the most updated recommendations for the treatment of COVID-19. We previously reported the presence of almost all the receptors of SARS-CoV-2 on cardiomyocytes which makes the heart a favorable target for this virus 3 . Batta et al 2 indicated that the vascular endothelial dysfunction is involved in the pathogenesis of SARS-CoV-2 and hence the activation of pro-inflammatory cytokines leading to increased vascular permeability and thrombosis in many organs.

Tachycardia was the most common cardiac presentation associated with SARS-CoV-2 infection, along with arrhythmias and conduction blocks, myocardial ischemia and injury, and hypertension. Interestingly, the authors reported that the elevated ACE-2 expression on endothelial cells of COVID -19 patients’ lungs indicates an elevated pro-hypertensive angiotensin II level leading to vasoconstriction and aldosterone-driven hypervolemia. Thus, the use of renin-angiotensin-aldosterone inhibitors in hypertension treatment of patients infected with SARS-CoV-2 was cautioned to avoid exacerbated cardiovascular clinical outcome.

An article from Gonzalez-Gonzalez et al. 4 reviewed the application of Virchow’s Triad in detail for the risk of developing stroke and related intravascular thrombotic diseases in the context of COVID-19 infection. The authors discussed each part of Virchow’s triad in detail, such as hypercoagulable state, vascular damage, and intravascular stasis of blood. They looked into literature on the effects of COVID-19 infection for the formation of intravascular and intracardiac clots (leading to stroke), formation of cardiac sequelae and autopsy studies reporting elevated markers in ventricular myocardium. The authors reviewed the risk factor for stroke development, differences between ischemic vs haemorrhagic stroke and frequent complications of COVID-19 patients such as pulmonary embolism. The authors also discussed the current treatment plans and recommended some differential treatment approaches for COVID-19 infection patients concerning known mechanisms of Virchow’s triad. Finally, the authors discussed the outcomes and long-term consequences of COVID-19 infection and the cardiovascular effects of COVID-19 vaccines.

The work from A. Mujalli and co-workers 5 investigated genetic pathways in patients with severe COVID-19 and comorbidities, by means of genome-wide transcriptomic datasets publicly available within the first year of the pandemic. Differential gene expression (DGE), gene ontology (GO), pathway enrichment, functional similarity, phenotypic analysis and drug target identification studies were conducted using a cohort of 120 COVID-19 patients, 281 patients with chronic comorbidities (153 CVD, 64 atherosclerosis, 33 diabetes, and 31 obesity), and 252 patients with different infectious diseases (145 respiratory syncytial virus, 95 influenza, and 12 MERS). In total, 29 genes were identified to contributing to the clinical severity of COVID-19 infection in patients with comorbidities. Remarkably, identified genes were found to be involved in immune cell homeostasis during innate immunity, mostly in monocyte and macrophage function. In addition, results from drug target identification studies show a mismatch between the currently used drugs in COVID-19 therapy and predicted drugs against identified genes.

Furtheremore, in this issue of the Journal, Chan et al 6 examined the association of COVID-19 with heart rate (HR) and blood pressure (BP) variability during exercise in a cohort of 18 patients with prior COVID-19 infection (equally split between symptomatic and asymptomatic), and a cohort of 9 controls who were never infected with COVID-19. Using a rigorous experimental design, the investigators measured HR and BP at regular intervals before, during, and after submaximal exercise, and quantified HR and BP variability on time and frequency domains. Baseline HR and BP were not significantly different between groups (symptomatic vs. asymptomatic vs. controls), nor were they different after completing a bout of submaximal exercise at a comparable workload. However, HR and BP variability was blunted only in individuals with prior symptomatic COVID-19 infection, but not in controls or those with a prior asymptomatic infection, suggesting an underlying degree of autonomic nervous system dysfunction in affected individuals.

The authors are to be lauded for their elegant and clinically relevant work, despite the obvious limitation of small sample size, since it provides much needed insight into COVID-19-induced abnormalities in cardiac physiology. The current findings provide a potential explanation for exercise intolerance, a frequently reported long-term symptom among survivors of COVID-19, since blunting of HR and BP variability are markers of impaired parasympathetic nervous system and poor cardiovascular health.In conclusion, the COVID-19 pandemic affected millions around the globe before it started abating with the advent of the emergent vaccines that were approved for use on emergency basis.

The WHO declared the end of the pandemic after three years of its surge. While millions succumbed to this deadly respiratory infection, survivors from this illness, particularity those who were severely sick, are reporting cardiac and nervous abnormalities. We hope that this series provides a new perspectives on the manifestations of COVID-19 in the heart, the brain, and the vasculature with the hope to guide therapeutic interventions for patients suffering from long term sequelae of SARS-CoV-2 infection.

Source: Moni Nader1, Georges E. Haddad, Jacobo Elies, Sriharsha Kantamneni and Firas Albadarin. Physiological underpinnings of long COVID: what have we learned? Front. Physiol. Sec. Clinical and Translational Physiology. Volume 14 – 2023 | doi: 10.3389/fphys.2023.122455 https://www.frontiersin.org/articles/10.3389/fphys.2023.1224550/full (Full text)

Long COVID is primarily a Spike protein Induced Thrombotic Vasculitis

Abstract:

Long COVID describes an array of often debilitating symptoms in the aftermath of SARS-CoV-2 infection, with similar symptomatology affecting some people post-vaccination. With an estimated > 200 million Long COVID patients worldwide and cases still rising, the effects on quality of life and the economy are significant, thus warranting urgent attention to understand the pathophysiology. Herein we describe our perspective that Long COVID is a continuation of acute COVID-19 pathology, whereby coagulopathy is the main driver of disease and can cause or exacerbate other pathologies common in Long COVID, such as mast cell activation syndrome and dysautonomia.
Considering the SARS-CoV-2 spike protein can independently induce fibrinaloid microclots, platelet activation, and endotheliitis, we predict that persistent spike protein will be a key mechanism driving the continued coagulopathy in Long COVID. We discuss several treatment targets to address the coagulopathy, and predict that (particularly early) treatment with combination anticoagulant and antiplatelet drugs will bring significant relief to many patients, supported by a case study. To help focus attention on such treatment targets, we propose Long COVID should be referred to as Spike protein Induced Thrombotic Vasculitis (SITV). These ideas require urgent testing, especially as the world tries to co-exist with COVID-19.

Source: Kerr R, Carroll HA. Long COVID is primarily a Spike protein Induced Thrombotic Vasculitis. Research Square; 2023. DOI: 10.21203/rs.3.rs-2939263/v1. https://assets.researchsquare.com/files/rs-2939263/v1_covered_7190a867-1475-4b57-b220-716a953649f1.pdf?c=1684433225 (Full text)

Thromboembolism in the Complications of Long COVID-19

Abstract:

SARS-CoV-2 is a +ssRNA helical coronavirus responsible for the global pandemic caused by coronavirus disease 19 (COVID-19). Classical clinical symptoms from primary COVID-19 when symptomatic include cough, fever, pneumonia or even ARDS; however, they are limited primarily to the respiratory system. Long-COVID-19 sequalae is responsible for many pathologies in almost every organ system and may be present in up to 30% of patients who have developed COVID-19.

Our review focuses on how long-COVID-19 (3 -24 weeks after primary symptoms) may lead to an increased risk for stroke and thromboembolism. Patients who were found to be primarily at risk for thrombotic events included critically ill and immunocompromised patients. Additional risk factors for thromboembolism and stroke included diabetes, hypertension, respiratory and cardiovascular disease, and obesity.

The etiology of how long-COVID-19 leads to a hypercoagulable state are yet to be definitively elucidated. However, anti-phospholipid antibodies and elevated D-dimer are present in many patients who develop thromboembolism. In addition, chronic upregulation and exhaustion of the immune system may lead to a pro-inflammatory and hypercoagulable state, increasing the likelihood for induction of thromboembolism or stroke. ‘

This article provides an up-to-date review on the proposed etiologies for thromboembolism and stroke in patients with long-COVID-19 and to assist health care providers in examining patients who may be at a higher risk for developing these pathologies.

Source: Leilani A Lopes, Devendra K Agrawal. Thromboembolism in the Complications of Long COVID-19. Cardiology and Cardiovascular
Medicine. 7 (2023): 123-128. https://fortunepublish.com/articles/10.26502.fccm.92920317.pdf (Full text)