Mechanisms of platelet activation in recovered COVID-19 patients
- Conditions
- COVID-19
- Registration Number
- DRKS00025217
- Lead Sponsor
- Institut für Pharmakologie, Universitätsmedizin Greifswald
- Brief Summary
In early 2020, coronavirus disease 2019 (COVID 19) led to a global state of emergency resulting in an ongoing pandemic for over three years. Severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) is now an everyday companion from which thousands of people keep struggling with persistent symptoms even after the infection. Although we know the disease can cause thrombotic events due to hyperinflammation and hypercoagulability, platelet reactivity after a mild course of the infection needs to be further investigated. We conducted a cohort study with COVID-19 patients 2 15 weeks (n = 28) and 6–9 months (n = 17) after a mild COVID 19 infection (convalescent group) and healthy control individuals matched by age and sex. Parameters of platelet aggregation and coagulation as well as platelet activation markers were determined ex vivo. We observed that robust platelet functions such as platelet aggregation determined by light transmission aggregometry, and thrombin formation measured by calibrated automated thrombography were not altered in convalescents compared to control individuals. However, an elevation in subtle platelet activation markers such as P-selectin (CD62P) surface expression and activation of glycoprotein IIb/IIIa (GPIIb/IIIa; PAC-1 binding) was observed 2-15 weeks after infection. This was accompanied by an increased expression of the transporter multidrug resistance protein 4 (MRP4/ABCC4) in platelets and with significantly elevated levels of the immunomodulatory mediator sphingosine-1-phosphate (S1P) in platelet-poor plasma of convalescents. These findings suggest an increased platelet sensitization and pro-inflammatory state even after recovery from a mild course of COVID-19 that could particularly be related to prolonged symptoms of COVID 19.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 56
1. able to provide informed consent
2. Individuals who have been infected and had a mild COVID-19 disease (reconvalescents). These individuals had typical symptoms for at least 5 days but have never been treated in the hospital. These individuals are fully receovered at study inclusion.
3. Individuals who have been infected and had a severe COVID-19 disease (reconvalescents). These individuals were hospitalized for COVID-19 disease. These individuals are fully receovered at study inclusion.
4. Healthy volunteers never infected with SARS-CoV-2 (control group).
1. Intake (regular or acute within 7 days of blood sample) of drugs interfering with platelet function (e.g. acetyl salicylic acid, ibuprofen, antidepressants of SSRI and SSNRI class).
2. platelet dysfunction or thrombocytopenia
3. pregancy and lactation period
Study & Design
- Study Type
- observational
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Difference in platelet activation measured by light transmission aggregation
- Secondary Outcome Measures
Name Time Method 1. Formation of thrombin by Calibrated Automated Thrombogram<br>2. Determination of specific markers of platelet activation (e.g. CD62, PAC1) <br>3. Determination of platelet surface markers Bestimmung von (e.g. CD62, CD63, GPVI, HLA)<br>4. Influence of MRP4 inhibition with Ceefourin-1 on pletelet function<br>5. MRP4 expression and factors of S1P metabolism in pletelets<br>6. S1P concentrationen and thromboxan B2 concentration in plasma<br>7. pletelet count<br>8. SARS-CoV-2 antibodies in serum