Tag: platelet dysfunction

Vascular inflammation in neuropsychiatric long COVID

Highlights:

  • Long COVID is characterized by endothelial dysfunction with dysregulated inflammatory and coagulation pathways.
  • Endothelial biomarkers are elevated in Long COVID vs acute COVID-19, supporting a distinct vascular process.
  • Vascular biomarkers correlate with key cognitive and neuropsychiatric measures (fluency, memory, depression, and anxiety).
  • Vascular inflammation is a targetable mechanism in Long COVID, informing patient stratification and therapeutic trials.
  • Results highlight need to define the short- and long-term impact of vascular inflammation on brain health after COVID-19.

Abstract

The role of vascular inflammation in neuropsychiatric Long COVID (LC) is suspected but not well understood. This study evaluated whether vascular inflammation is present in individuals with neuropsychiatric LC and how it relates to cognitive and mental health symptoms.

This cross-sectional, case-control study included individuals with acute COVID-19 (AC), neuropsychiatric LC, and recovered controls. Participants were enrolled from the COVID Mind Study and the Yale IMPACT Study (hospitalized), and an independent cohort from the Johns Hopkins University (JHU) Long COVID Study. Fifty individuals with neuropsychiatric LC (new symptoms a median of 368 days post-COVID), 28 with AC, and 29 recovered controls (>3 months post-COVID) were evaluated. All underwent blood sampling and neuropsychiatric testing. The JHU cohort included 114 individuals with late LC (median 1065 days post-COVID illness associated with LC onset) and 31 recovered controls (median 852 days).

Fourteen plasma biomarkers of vascular inflammation were measured. ANCOVA was used to compare groups, adjusting for comorbidities. Non-hospitalized participants completed the Global Neuropsychological Assessment, GAD-7, and PHQ-9. LC and recovered groups were demographically similar, while AC participants had higher obesity and hypertension rates. LC participants had elevated circulating biomarkers of endothelial, leukocyte, and platelet adhesion (sL-selectin, ADAMTS13, sP-selectin, sICAM-1) compared to recovered controls.

Coagulation markers (D-dimer, fibrinogen) did not differ. Most biomarkers were highest in AC and lower in LC; however, fetuin, sL-selectin, and α-2 macroglobulin were higher in LC than AC. In LC, higher sP-selectin correlated with lower fluency and verbal learning. Lower α1-acid glycoprotein levels were strongly associated with poorer verbal memory, verbal learning, fluency, depression, and anxiety. In the JHU cohort, late LC and recovered controls showed no differences in biomarkers or demographics, suggesting normalization over time. Persistent dysregulation at the intersection of inflammation, platelet adhesion, and endothelial dysfunction is strongly linked to neuropsychiatric Long COVID.

Elevated markers of endothelial adhesion in LC suggest distinct pathophysiology from AC. These biomarkers correlate with lower fluency and verbal learning, linking vascular dysfunction to brain function. This study underscores the critical need for longitudinal, within-person investigations to elucidate how vascular inflammation evolves over time.

Source: McAlpine LS, Shorer EF, Chiarella J, Nelson A, Veenhuis R, Azola A, Lee A, Pierce R, Farhadian S, Rubin LH, Spudich SS; Yale COVID Mind; IMPACT Study Groups. Vascular inflammation in neuropsychiatric long COVID. Brain Behav Immun Health. 2026 Apr 28;54:101247. doi: 10.1016/j.bbih.2026.101247. PMID: 42099668; PMCID: PMC13147379. https://pmc.ncbi.nlm.nih.gov/articles/PMC13147379/ (Full text)

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

Postural orthostatic tachycardia syndrome is associated with platelet storage pool deficiency

Abstract:

Mechanisms have been postulated to explain postural orthostatic tachycardia syndrome (POTS), however, the etiology of this often debilitating disorder remains unknown. We conducted a retrospective case-control study of 181 POTS patients who exhibited/reported bleeding symptoms for a specific platelet (PL) dysfunction disorder, delta granule storage pool deficiency (δ-SPD).Patients were included only if results of blood tests for δ-SPD were available.

Electron microscopy was utilized to diagnose δ-SPD. An ELISA assay was used to determine serotonin (5HT) concentration in PLs and medical record review was employed to collect patients’ clinical symptoms.The most common bleeding symptom was easy bruising (71%) but frequent nose bleeds, heavy menstrual bleeding, and a family history of bleeding were also commonly reported. Of the patients studied, 81% were diagnosed with δ-SPD.

Our investigation of 5HT concentration extracted from PLs revealed significantly lower levels of 5HT in POTS patients when compared to that of control subjects. Our data suggest that patients with POTS have significant comorbidities including bleeding symptoms and/or family bleeding histories, and have diminished PL 5HT levels supporting the hypothesis that POTS is a low 5HT level disorder.

While we describe a significant relationship with POTS and δ-SPD, this finding does not constitute an etiology for POTS.Our results establish an additional comorbidity frequently seen in POTS that could explain a number of disparate symptoms often affecting the severity of POTS.

Source: Gunning WT 3rd, Karabin BL, Blomquist TM, Grubb BP. Postural orthostatic tachycardia syndrome is associated with platelet storage pool deficiency. Medicine (Baltimore). 2016 Sep;95(37):e4849. doi: 10.1097/MD.0000000000004849. PMID: 27631244; PMCID: PMC5402587. https://pmc.ncbi.nlm.nih.gov/articles/PMC5402587/ (Full text)