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

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

Interventions

GENETIC

Complete thrombophilic profile testing by multiplex PCR

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

Sponsors & Collaborators

• Grigore T. Popa University of Medicine and Pharmacy

  lead OTHER

Principal Investigators

• Adrian Covic, Professor · Gr T Popa University of Medicine and Pharmacy Iasi ROMANIA

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-08-18

Primary Completion

2021-02-17

Completion

2021-08-18

Countries

• Romania

Study Locations