Impact of Antiphospholipid Antibodies on Thrombin Generation During Sars-CoV2 Infection (TACIT2 Study) (TACIT2)

Impact of Antiphospholipid Antibodies on Thrombin Generation During Sars-CoV2 Infection.

Context: Until 70% of thrombotic event are reported during Sars-CoV2 infection. Antiphospholipid antibodies (aPL) tests are often positive. We aim to determine if aPL positivity is involved in thrombose of Sars-CoV2 infection investigating the effect of aPL on thrombin generation (TG) and leucocyte pathway activation (neutrophils extracellular traps (NETs) and activation of triggering receptor expressed on myeloid cells 1 (TREM-1)).

Method: We will compare plasma from five groups of subjects: patients with antiphospholipid syndrome (APS) and patients hospitalized for Sars-CoV-2 infection with or without aPL, and as control, patients with acute venous thromboembolism event and healthy volunteers. For each subject, we will analyze aPL, activated protein C (APC) resistance measured by TG and leukocytes markers as circulating neutrophils extracellular traps (NETs) and soluble triggering receptor expressed on myeloid cells one (sTREM-1). We will control aPL test at three month and analyze their persistent positivity and association with thrombotic event.

Results: we hypothesize that patients with COVID-19 and aPL will have a similar aPL and level of APS resistance that patients with APS. Also, we think that circulating NETs and sTREM-1 levels will be more important in patients with COVID-19 with aPL than patients without aPL and similar in patients with COVID-19 and aPL and patients with APS.

Conclusion: our study will be the first to analyze the potential role of aPL on APC resistance measured by TG and neutrophil activation in COVID-19.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19; Antiphospholipid Syndrome
• Intervention / Treatment: Diagnostic test: characterization of aPL

• Study Type: Observational
• Enrollment (Anticipated): 161

Contacts and Locations

• Study Contact: Name: Stéphane Zuily, MD, PhD; Phone Number: +33383157354; Email: s.zuily@chru-nancy.fr
• Study Contact Backup: Name: Virginie DUFROST, MD; Phone Number: +33383157828; Email: v.dufrost@chru-nancy.fr

Study Locations

• France
  • Nancy, France, 54500
    • Virginie Dufrost
    • Contact: Virginie DUFROST, MD
    • Principal Investigator: Stéphane Zuily, MD, PhD
    • Sub-Investigator: Denis G Wahl, MD, PhD
    • Sub-Investigator: Thomas Foret, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Five groups of subjects will be enrolled in the study :

1. patients hospitalized for à COVID-19 with aPL
2. patients hospitalized for à COVID-19 without aPL
3. patients with APS
4. as control, patients with acute venous thromboembolism disease
5. as control, healthy volunteers.

Description

Inclusion Criteria:

• Patient receiving a comprehensive information about the study, and not opposed to participate

  + one criterion among :

• patient hospitalized fo a COVID-19
• Patient with known APS
• Patients hospitalized for an acute venous thromboembolism event aPL positivity or COVID-19
• healthy volunteers

Exclusion Criteria:

• For all participants : pregnancy, age below 18 years-old, absence of written informed consent , autoimmune or inflammatory disease except antiphospholipid syndrome
• For patients with COVID-19: previous aPL positivity (before COVID-19 infection)
• For patients with APS: previous symptomatic COVID-19 infection
• For patients control with acute venous thromboembolism event: previous symptomatic COVID-19 infection, infection or inflammatory disease in flare at the time of thromboembolism event, known aPL positivity
• For Healthy volunteers: history of thrombosis (venous, arterial or small vessels), previous symptomatic COVID-19 infection, infection or inflammatory disease in flare at the time of inclusion, known aPL positivity

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy control	Diagnostic test: characterization of aPL; characterization of aPL profile, GT profile and leukocytes activations markers (NETs, TREM-1)
Patients with COVID-19 and aPL positivity; Patient with COVID-19 and aPL test positivity	Diagnostic test: characterization of aPL; characterization of aPL profile, GT profile and leukocytes activations markers (NETs, TREM-1)
Patients with COVID-19 without aPL positivity	Diagnostic test: characterization of aPL; characterization of aPL profile, GT profile and leukocytes activations markers (NETs, TREM-1)
APS patients	Diagnostic test: characterization of aPL; characterization of aPL profile, GT profile and leukocytes activations markers (NETs, TREM-1)
Disease control	Diagnostic test: characterization of aPL; characterization of aPL profile, GT profile and leukocytes activations markers (NETs, TREM-1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of activated protein C resistance and comparison between groups	at inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
frequency of positivity of each aPL test and comparison between groups	at inclusion
concentration of leucocytes activation markers and comparison between groups	at inclusion
frequency of persistent aPL test positivity and comparison between groups	at three month

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Study Director: Denis G Wahl, MD, PhD, CHRU of Nancy; Principal Investigator: Stéphane Zuily, MD, PhD, CHRU of Nancy; Principal Investigator: Virginie Dufrost, MD, PhD, CHRU of Nancy

Publications and helpful links

General Publications

• Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP, MacDonald V, Green L, Sivapalaratnam S, Pasi KJ, MacCallum P. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19. N Engl J Med. 2020 Jul 16;383(3):288-290. doi: 10.1056/NEJMc2013656. Epub 2020 May 5. No abstract available.
• Zuily S, de Laat B, Guillemin F, Kelchtermans H, Magy-Bertrand N, Desmurs-Clavel H, Lambert M, Poindron V, de Maistre E, Dufrost V, Risse J, Shums Z, Norman GL, de Groot PG, Lacolley P, Lecompte T, Regnault V, Wahl D. Anti-Domain I beta2-Glycoprotein I Antibodies and Activated Protein C Resistance Predict Thrombosis in Antiphospholipid Syndrome: TAC(I)T Study. J Appl Lab Med. 2020 Nov 1;5(6):1242-1252. doi: 10.1093/jalm/jfaa072.
• Yalavarthi S, Gould TJ, Rao AN, Mazza LF, Morris AE, Nunez-Alvarez C, Hernandez-Ramirez D, Bockenstedt PL, Liaw PC, Cabral AR, Knight JS. Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: a newly identified mechanism of thrombosis in the antiphospholipid syndrome. Arthritis Rheumatol. 2015 Nov;67(11):2990-3003. doi: 10.1002/art.39247.
• Edel Y, Kliminski V, Pokroy-Shapira E, Oren S, Dortort Lazar A, Pri-Paz Basson Y, Egbaria M, Molad Y. Elevated plasma level of soluble triggering receptor expressed on myeloid cells-1 is associated with inflammation activity and is a potential biomarker of thrombosis in primary antiphospholipid syndrome. Arthritis Res Ther. 2019 Jan 7;21(1):10. doi: 10.1186/s13075-018-1779-5.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: November 18, 2021
• First Submitted That Met QC Criteria: November 18, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Actual): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Autoimmune Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Antiphospholipid Syndrome
• Other Study ID Numbers: 2021-A00244-37

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No