Investigating the Involvement of ACE and Angiotensinogen Genes' Polymorphism Along With Other Thrombophilic Genotypes in Severe Forms of COVID-19 With/Without Thrombotic Events

NCT04519398 | Unknown DMC

• 1 other identifier: GTP0051
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

An estimated 22% of the global population is at an increased risk of a severe form of COVID-19, while one in four coronavirus patients admitted to intensive care unit will develop a pulmonary embolism. A major public health question remains to be investigated: why COVID-19 is mild for some, critically severe for others and why only a percentage of COVID-19 patients develop thrombosis, despite the disease's proven hypercoagulable state? Patients' intrinsic characteristics might be responsible for the deep variety of disease forms. Our study aims to assess the validity of the hypothesis according to which underlining genetic variations might be responsible for different degrees of severity and thrombotic events risks in the novel coronavirus disease. Moreover, we suspect that prothrombotic genotypes occuring in the genes that encode angiotensin-converting enzyme (ACE-DEL/INS) and angiotensinogen (AGT M235T) are involved in the unpredictable evolution of COVID-19, both in terms of severity and thrombotic events, due to the strong interactions of SARS-CoV-2 with the renin-angiotensin-aldosterone system (RAAS). Therefore, we also aim to assess the validity of the theory according to which there is a pre-existing atypical modulation of RAAS in COVID-19 patients that develop severe forms and/or thrombosis. Our hypothesis is based on various observations. Firstly, there is a substantial similarity with a reasonably related condition such as sepsis, for which there is a validated theory stating that thrombophilic mutations affect patients' clinical response. Secondly, racial and ethnic genetic differences are responsible for significant dissimilar thrombotic risks among various nations. Thirdly, an increase in stroke incidence has been reported in young patients with COVID-19, without essential thrombosis risk factors, favoring the idea that a genetic predisposition could contribute to increase the thrombotic and thromboembolic risk. Fourthly, the plasminogen activator inhibitor (PAI)-1 4G/5G inherited mutation was found to be responsible for a thrombotic state causing post-SARS osteonecrosis.

Conditions

Covid19; Corona Virus Infection; Thrombosis; ARDS; Thrombophilia; Thromboses, Intracranial; Thromboses, Deep Vein; RAAS

Keywords

Covid-19; COVID-19 severity; Thrombosis; Thrombophilia; thrombophylic profile; Renin-angiotensin-aldosterone system alterations

Outcome Measures

Primary Outcomes (1)

• Number of patients with thrombophilic profile alterations

  The difference of prothrombotic genotypes frequency between the three groups

  One year

Secondary Outcomes (1)

• Number of patients with RAAS components alterations

  One year

Study Arms (3)

COVID-19 patients with proved venous thrombosis

1st group includes COVID-19 patients with proved * venous thrombosis (deep vein thrombosis, pulmonary embolism or venous thrombosis occurring in more atypical places such as in the veins of the brain, liver, kidney, mesenteric vein and the veins of the arms) * or arterial thrombosis (heart attacks, strokes)

Genetic: Complete thrombophilic profile testing by multiplex PCR

Asymptomatic COVID-19 & those with mild or moderate disease

2nd group encompasses asymptomatic patients and those with mild or moderate disease, according to current guidelines, without thrombosis: no symptoms or evidence of lower respiratory disease by clinical assessment or imaging and a SpO2 \> 94%

Genetic: Complete thrombophilic profile testing by multiplex PCR

Severe disease, according to Guidelines, without thrombus

3rd group includes severe disease, according to current guidelines, without thrombosis: respiratory frequency \> 30 breaths per minute, SpO2 \< 94%, PaO2/FiO2 \< 300 mmHg, or lung infiltrates \>50%

Genetic: Complete thrombophilic profile testing by multiplex PCR

Interventions

Complete thrombophilic profile testing by multiplex PCR GENETIC

Complete thrombophilic profile testing by multiplex PCR and reverse hybridization of DNA to assess the presence of prothrombotic genotypes: * Factor V Leiden * Factor V 4070 A\>G (Hr2) * Factor II G20210A * Methylenetetrahydrofolate reductase (MTHFR) C677T * MTHFR A1298C * Cystathionine β-synthase (CBS) 844ins68 * PAI-1 4G/5G * Glycoprotein IIIa T1565C (HPA-1a/b) * ACE-DEL/INS * Apolipoprotein E (ApoE) * AGT M235T * Angiotensin II type 1 receptor (ATR-1) A1166C * Fibrinogen - 455 G\>A * Factor XIII Val34Leu

Asymptomatic COVID-19 & those with mild or moderate disease; COVID-19 patients with proved venous thrombosis; Severe disease, according to Guidelines, without thrombus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients with COVID-19 and thrmbotic events or, Patients with COVID-19 \& no thrombotic events but with a severe form Patients with COVID-19 \& no thrombotic events and no or mild symptoms

You may qualify if:

• All hospitalized patients with cough, fever, myalgia - with confirmed COVID-19 infection • All patients with a positive SARS-CoV-2 PCR test

You may not qualify if:

• Patient refusal
• Uncertain tests results
• Children

Sponsors & Collaborators

• Grigore T. Popa University of Medicine and Pharmacy: lead

Study Sites (1)

University of Medicine and Pharmacy Gr T. Popa Iasi, Romania

Iași, 700503, Romania

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood with complete thrombophilic profile testing and RAAS components assessment through PCR (multiplex PCR and reverse hybridization of DNA to assess the presence of prothrombotic genotypes)

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Thrombosis; Thrombophilia; Intracranial Thrombosis; Venous Thrombosis

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Intracranial Embolism and Thrombosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Thromboembolism

Study Officials

• Adrian Covic, Professor

  Gr T Popa University of Medicine and Pharmacy Iasi ROMANIA

  STUDY CHAIR

Central Study Contacts

Alexandru Burlacu, MD, PhD

CONTACT

00407444488580; alexandru.burlacu@umfiasi.ro

Radu Crisan-Dabija, MD, PhD

CONTACT

radu.dabija@umfiasi.ro

Study Design

• Study Type: observational
• Observational Model: ECOLOGIC OR COMMUNITY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: August 19, 2020
• Study Start: August 18, 2020
• Primary Completion: February 17, 2021
• Study Completion: August 18, 2021
• Last Updated: August 19, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

RO (1)