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

NCT07400848 | Recruiting

• 1 other identifier: 2025-01382
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Vaccine-Related Adverse Event; Endothelial Dysfunction; Coagulation Abnormalities; Inflammation; Cytokines; Patient-Reported Outcomes; Symptom Burden; Disease Trajectory; Reactive Hyperemia Index

Outcome Measures

Primary Outcomes (3)

• Self-reported health status (EQ-VAS)

  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.

  From enrollment to baseline assessment (T0)

• Health-related quality of life (EQ-5D-5L index score)

  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.

  From enrollment to baseline assessment T0

• Reactive Hyperemia Index (lnRHI)

  Continuous Reactive Hyperemia Index measured using EndoPAT; noting that values ≤0.51 indicating dysfunction

  From enrollment to the day of examination, estimated to occur within 14 days after enrollment.

Secondary Outcomes (24)

• 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.

Study Arms (2)

Post-Acute COVID-19 Vaccination Syndrome Patients

Diagnostic Test: Blood sampling and analysis; Other: The continuous Reactive Hyperemia Index (InRHI) measured by EndoPAT

Healthy controls

Matched (similar age (±10 years) and sex)

Diagnostic Test: Blood sampling and analysis; Other: The continuous Reactive Hyperemia Index (InRHI) measured by EndoPAT

Interventions

The continuous Reactive Hyperemia Index (InRHI) measured by EndoPAT OTHER

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.

Healthy controls; Post-Acute COVID-19 Vaccination Syndrome Patients

Blood sampling and analysis DIAGNOSTIC_TEST

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)

Healthy controls; Post-Acute COVID-19 Vaccination Syndrome Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Progress:The study aims to enrol approximately 150-200 adults (≥18 years) who report persistent and severe symptoms following COVID-19 vaccination. Endoclot/Real: The study includes 40 individuals with suspected PACVS who meet criteria for ME/CFS and PEM, as identified through the PROGRESS subproject. Each patient is matched with a healthy control of similar age (±10 years) and sex. Control participants must have received a COVID-19 vaccination but report no persistent adverse effects and no chronic illness.

You may qualify if:

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

You may not qualify if:

• Severe cognitive, physical impairment or psychiatric conditions impeding participation
• Active oncological disease or immunosuppressive
• Known pregnancy at the time of enrolment
• PROGRESS (patients only)
• 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
• ENDOCLOT and REAL (patients and matched healthy controls)
• 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.
• \. For controls: History of COVID-19 vaccination without persistent adverse effects; age (+/- 10 years), and sex match to a corresponding case

Sponsors & Collaborators

• University of Bern: lead
• private practice Cell-Re-Active-Training in Bern: collaborator
• Post-Vakzin-Syndrom Schweiz: collaborator
• Medical University Innsbruck: collaborator

Study Sites (1)

Institute of Sport Science, University of Bern

Bern, 3012, Switzerland

RECRUITING

MeSH Terms

Conditions

Fatigue Syndrome, Chronic; Inflammation

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Mirko Schmidt, Prof. Dr.

  Institute of Sport Science, University of Bern, Switzerland

  PRINCIPAL INVESTIGATOR

• Dieter Thommen, Dr.med.

  Praxis für Cell-Re-Active-Training, Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mirko Schmidt, Prof. Dr.

CONTACT

+41 79 342 67 30; CLEAR.ispw@unibe.ch

Michaela Fux, PD Dr. phil. nat.

CONTACT

+41 79 342 67 30; CLEAR.ispw@unibe.ch

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: February 10, 2026
• Study Start: March 22, 2026
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): November 15, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)