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

Обзор

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.

Вмешательства

• Диагностический тест 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)
• Другое 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 press

Первичные конечные точки

• Self-reported health status (EQ-VAS) [Срок оценки: From enrollment to baseline assessment (T0)]
• Health-related quality of life (EQ-5D-5L index score) [Срок оценки: From enrollment to baseline assessment T0]
• Reactive Hyperemia Index (lnRHI) [Срок оценки: From enrollment to the day of examination, estimated to occur within 14 days after enrollment.]

Вторичные конечные точки (12)

• Change in self-reported health status (EQ-VAS) [Срок оценки: During follow-up at approximately 4 months (±2 weeks, T1) and 8 months (±2 weeks; T2) after enrollment.]
• Change in health-related quality of life (EQ-5D-5L index score) [Срок оценки: During follow-up at approximately 4 months (±2 weeks, T1) and 8 months (±2 weeks, T2) after enrollment.]
• Functional impairment (Bell Disability Scale) [Срок оценки: From enrollment to baseline assessment (T0), and during follow-up at approximately 4 months (±2 weeks, T1) and 8 months (±2 weeks, T2) after enrollment.]
• ME/CFS symptom severity (Canadian Consensus Criteria) [Срок оценки: From enrollment to baseline assessment (T0), and during follow-up at approximately 4 months (±2 weeks, T1) and 8 months (±2 weeks, T2) after enrollment.]
• Presence of post-exertional malaise (PEM) [Срок оценки: From enrollment to baseline assessment (T0), and during follow-up at approximately 4 months (±2 weeks, T1) and 8 months (±2 weeks, T2) after enrollment.]
• Functional capacity (FUNCAP55) [Срок оценки: From enrollment to baseline assessment (T0), and during follow-up at approximately 4 months (±2 weeks, T1) and 8 months (±2 weeks, T2) after enrollment.]
• Reported treatments and medications [Срок оценки: From enrollment to baseline assessment (T0), and during follow-up at approximately 4 months (±2 weeks, T1) and 8 months (±2 weeks, T2) after enrollment.]
• Self-reported treatment effects and side effects [Срок оценки: From enrollment to baseline assessment (T0), and during follow-up at approximately 4 months (±2 weeks, T1) and 8 months (±2 weeks, T2) after enrollment.]
• Platelet reactivity (ADPtest AUC) [Срок оценки: From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.]
• Platelet reactivity (ASPItest AUC) [Срок оценки: From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.]
• Platelet reactivity (TRAPtest AUC) [Срок оценки: From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.]
• High-sensitivity C-reactive protein (hs-CRP) level [Срок оценки: From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.]

Критерии участия

General Criteria (apply to all study parts: PROGRESS, ENDOCLOT, REAL, patients and matched healthy controls)

Критерии включения

• Age ≥ 18 years
• Sufficient knowledge of German to complete study-related questionnaires and procedures

Критерии исключения

• Severe cognitive, physical impairment or psychiatric conditions impeding participation
• Active oncological disease or immunosuppressive
• Known pregnancy at the time of enrolment

PROGRESS (patients only)

Критерии включения

• Coded participation with online consent confirmation
• Self-reported onset of persistent symptoms temporally associated with a COVID-19 vaccination
• Willingness and ability to participate in the 8-month follow-up period

Критерии исключения

1\. No specific exclusion criteria for this part

ENDOCLOT and REAL (patients and matched healthy controls)

Критерии включения

• Signed informed consent form
• For patients:

• Receipt of at least one COVID-19 vaccination
• Onset of new, otherwise unexplained symptoms within 0-14 days after vaccination
• Persistence of symptoms for at least 6 months following vaccination
• Selection is based on a diagnosis of ME/CFS according to the Canadian Consensus Criteria (CCC) and PEM.

2\. For controls: History of COVID-19 vaccination without persistent adverse effects; age (+/- 10 years), and sex match to a corresponding case

Exclusion Criteria (patients and matched healthy controls)

• Clinically suspected or laboratory confirmed SARS-CoV-2 infection after vaccination or temporally related to symptom onset.
• Concurrent pre-existing Long COVID symptoms, obtained from the patient´s history
• Any self-reported or uncertain history of an acute infectious event (including mild or subclinical infections) in temporal proximity to COVID-19 vaccination
• Known pre-existing medical conditions or ongoing medications that could plausibly explain the reported symptoms (e.g., preexisting ME/CFS, POTS, fibromyalgia, small-fiberneuropathy, autoimmune disease with systemic involvement or other chronic multisystemic dysautonomia syndromes)
• Use of long-term, high-dose anti-inflammatory

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Швейцария · 1 центр

• Institute of Sport Science, University of Bern — Bern

Идентификаторы

NCT: NCT07400848 · 2025-01382

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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