NCT07400848

Clinical Laboratory Evaluation, Assessment of Symptoms and Recovery in Patients With Post-COVID-19-Vaccination Syndrome

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 200 (estimated)
• Sponsor: University of Bern · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Some people report persistent health problems after receiving the COVID-19 vaccine. These symptoms persist well beyond typical short-term vaccine side effects and are not attributable to any other known medical conditions. This condition is known as Post-Acute COVID-19 Vaccination Syndrome (PACVS). Symptoms can persist for months and affect several organ systems, causing issues such as fatigue, heart-related problems, neurological difficulties, and decreases in both physical ability and mental performance. PACVS shows similarities to Post-Acute COVID-19 syndrome (PACS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The biological processes that cause PACVS are still not fully understood. Recent research indicates that endothelial dysfunction, abnormalities in blood coagulation, and persistent inflammatory responses may contribute significantly to this process. However, it remains unclear how symptoms develop over time, which biological markers are associated with disease severity, and how these findings could support diagnosis and future treatment strategies. The CLEAR study is an observational research project designed to address these knowledge gaps by systematically documenting symptoms over time and investigating potential biological correlates in individuals affected by PACVS. The study consists of three complementary subprojects. The PROGRESS subproject aims to assess symptom burden, disease course, and patient-reported treatment experiences over an eight-month period using standardized questionnaires completed by participants. The ENDOCLOT subproject investigates whether individuals with PACVS show objective signs of endothelial dysfunction, abnormalities in blood clotting, and markers of systemic inflammation. Endothelial function will be evaluated through non-invasive vascular reactivity tests (EndoPAT), microscopic examination of blood cells, standardized platelet function assessments, and standard laboratory diagnostics. It further explores the correlation between these biological parameters and clinical symptom trajectories identified in PROGRESS. The REAL subproject examines the role of endothelial activation and the release of inflammatory signaling molecules (cytokines) in the development and persistence of PACVS. The main hypothesis of the CLEAR study is that PACVS is associated with measurable endothelial dysfunction, inflammatory activation, and coagulation abnormalities, and that these biological changes are related to symptom severity and persistence over time. By combining longitudinal symptom assessment with biological measurements, this study aims to improve understanding of PACVS and support the development of better diagnostic and therapeutic approaches in the future.

Conditions

• Post-Acute COVID-19 Vaccination Syndrome
• Postviral Fatigue

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Blood sampling and analysis	Blood sampling to analyze: 1. Routine laboratory diagnostics including complete blood count, coagulation and inflammation markers (e.g., fibrinogen, von Willebrand Factor, D-dimer, Factor VIII, hsCRP, Troponin-T, NT-proBNP 2. Platelet function analysis using the Multiplate Analyzer (ADPtest, ASPItest, TRAPtest) 3. Blood morphology assessment using real-time confocal microscopy 4. Endothelial activation (Syndecan-1, ICAM-1, PAI-1/tPA complex, Heparan sulfate) 5. Complement activation (sC5b-9)
OTHER	The continuous Reactive Hyperemia Index (InRHI) measured by EndoPAT	To assess endothelial function, participants undergo a non-invasive measurement using the EndoPAT device. This system evaluates vascular reactivity by continuously recording the peripheral arterial tone (PAT) signal via pneumatic finger probes placed on both index fingers. The total duration of the measurement is approximately 17 minutes. During the first 6 minutes, the baseline vascular tone is recorded at rest. This is followed by a 5-minute arterial occlusion phase, during which a blood pressure cuff on one arm (typically the non-dominant arm) is inflated to suprasystolic pressure to temporarily interrupt arterial blood flow. After the cuff is released, the reactive hyperemia response is recorded for an additional 6 minutes to assess endothelial-dependent vasodilation. The procedure is painless and well-tolerated. Participants may experience a mild tingling sensation in the occluded arm during the occlusion phase. No adverse effects are expected.

Timeline

• Start date: 2026-02-15
• Primary completion: 2026-05-15
• Completion: 2026-11-15
• First posted: 2026-02-10
• Last updated: 2026-02-10

Locations

1 site across 1 country: Switzerland