Clinical Laboratory Evaluation, Assessment of Symptoms and Recovery in Patients With Post-COVID-19-Vaccination Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Self-reported health status (EQ-VAS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General Criteria (apply to all study parts: PROGRESS, ENDOCLOT, REAL, patients and matched healthy controls)
- •Inclusion Criteria
- •Age ≥ 18 years
- •Sufficient knowledge of German to complete study-related questionnaires and procedures
排除标准
- •Severe cognitive, physical impairment or psychiatric conditions impeding participation
- •Active oncological disease or immunosuppressive
- •Known pregnancy at the time of enrolment
- •PROGRESS (patients only)
- •Inclusion Criteria
- •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
- •Exclusion Criteria
- •1. No specific exclusion criteria for this part
- •ENDOCLOT and REAL (patients and matched healthy controls)
- •Inclusion Criteria
- •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
研究组 & 干预措施
Post-Acute COVID-19 Vaccination Syndrome Patients
干预措施: Blood sampling and analysis (Diagnostic Test)
Healthy controls
Matched (similar age (±10 years) and sex)
干预措施: The continuous Reactive Hyperemia Index (InRHI) measured by EndoPAT (Other)
Post-Acute COVID-19 Vaccination Syndrome Patients
干预措施: The continuous Reactive Hyperemia Index (InRHI) measured by EndoPAT (Other)
Healthy controls
Matched (similar age (±10 years) and sex)
干预措施: Blood sampling and analysis (Diagnostic Test)
结局指标
主要结局
Self-reported health status (EQ-VAS)
时间窗: From enrollment to baseline assessment (T0)
Self-reported overall health status measured using the EuroQoL Visual Analogue Scale (EQ-VAS), ranging from 0 to 100, with higher scores indicating better perceived health status.
Health-related quality of life (EQ-5D-5L index score)
时间窗: From enrollment to baseline assessment T0
Health-related quality of life assessed using the EuroQoL EQ-5D-5L index score, typically ranging from values below 0 (health states worse than death) to 1, with higher scores indicating better health-related quality of life.
Reactive Hyperemia Index (lnRHI)
时间窗: From enrollment to the day of examination, estimated to occur within 14 days after enrollment.
Continuous Reactive Hyperemia Index measured using EndoPAT; noting that values ≤0.51 indicating dysfunction
次要结局
- Change in self-reported health status (EQ-VAS)(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)(During follow-up at approximately 4 months (±2 weeks, T1) and 8 months (±2 weeks, T2) after enrollment.)
- Functional impairment (Bell Disability Scale)(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)(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)(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)(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(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(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)(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- Platelet reactivity (ASPItest AUC)(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- Platelet reactivity (TRAPtest AUC)(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- High-sensitivity C-reactive protein (hs-CRP) level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- Fibrinogen level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- D-dimer level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- von Willebrand factor level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- Factor VIII activity(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- Troponin T (high sensitivity)(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- NT-proBNP level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- Blood cell morphology(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- Syndecan-1 level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- ICAM-1 level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- PAI-1/tPA complex level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- Heparan sulfate level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)
- Terminal complement complex (sC5b-9) level(From enrollment to the day of blood sampling, estimated to occur within 14 days after enrollment.)