Embolism in COVID-19 Positive Patients

Examining the Genetic Predisposition of Individuals Who Aggravated by Embolism in COVID-19 Positive Patients

Covid-19 outbreak has caused death of millions of people because of not only the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself but also infection dependent complications. Abnormalities in thrombotic events leads to some of these complications which eventually result in emboli. The endothelial damage caused by the virus interacting with ACE2 on the host cells leads to the activation of coagulation cascade. Accumulation of byproducts of the cascade might have some roles in embolism inducing risk of organ damage, other life-threatening problems, and even death. To enlighten the factors triggering embolism, the investigators have focused on genetic changes such as polymorphisms and mutations in certain genes in DNA samples coming from intensive care unit (ICU) patients.

Study Overview

• Status: Enrolling by invitation
• Conditions: Embolism; COVID-19 Pneumonia; Genetic Predisposition

Detailed Description

This study has conducted to find the possible links between genetic make up of ICU patients with severe Covid-19 and embolism. 13 polymorphisms and mutations that the investigators targeted are located on Factor II, Factor V, Factor XIII, MTHFR, angiotensin converting enzyme (ACE), endothelial cell protein C receptor (EPCR), and FGB. The investigators have found significant changes in the mutant allele frequencies in most of the factors.

The main workflow to study a point change on DNA sequence begins with DNA isolation from a biological material. In this case, we received blood samples in ethylenediaminetetraacetic acid (EDTA) tubes from ICU patients with severe Covid-19. The investigators hypothesis claims that genetic factors triggering thrombotic events might increase the severity of the diseases by inducing the risk of emboli.

After DNA isolation, desired loci on DNA were amplified via Polymerase Chain Reaction (PCR). Amplicons including the mutations and polymorphisms need to be purified before next generation sequencing (NGS).

The investigators analyze the data using Integrative Genomics Viewer (IGV) program and check the genetic profile (wt, het, mut). Some of the changes are meaningful by themselves while some other need to be considered as combinations. Compound heterozygosity and diagnosis for thrombophilia require cooccurrence of the changes.

To compare allelic frequencies, the investigators include the average of the data coming from more than 2000 individuals with no know thrombophilia cases. In the investigators focus cohort, the investigators have the data of 47 Covid-19 patients in ICU.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• Turkey
  • Cankaya
    • Ankara, Cankaya, Turkey, 06510
      • INTERGEN Genetics and Rare Diseases Diagnosis Research & Application Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Groups were assigned to determine the genetic factors that explain severity of COVID-19 infections. These genetic factors play role in thrombotic events in the body.

Case group involves ICU patients with emboli that suffer from severe COVID-19. The investigators expect to see some deviations from normal population regarding the mutations and polymorphisms related to thrombophilia. Control group is normal population representing the normal allelic frequencies of the determinant genetic factors.

Description

Inclusion Criteria:

• being tested positive for Covid-19
• ICU patients developing severe pneumonia upon Covid-19 infection

Exclusion Criteria:

• previously tested positive for genetic factors increasing thrombosis risk
• ICU patients developing severe emboli regardless of Covid-19 infection

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ICU patients with severe COVID-19 pneumonia; Without using any intervention, this group has been included in the study to research certain genetic dispositions determining the severity of the COVID-19 pneumonia
Random population; This group has been included as a control group to compare the genetic predisposition of ICU patients with severe COVID-19 pneumonia with the normal population.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in allelic frequencies in predetermined loci which are known to be related with thrombosis	In the first 28 samples the investigators received, we expected a predictive result revealing the genetic background and embolism in Covid-19. Deviations from allelic frequencies of healthy population regarding some of the factors will support the hypothesis of the study.	15.03.2021- 30.04.2021
An increase in thrombophilia cases in the study group	Thrombophilia is a complex state with the contribution of several factors. Clinical picture and the mutations enable the diagnosis. With an expanded study group consisting of 47 patients, we determined the patients with thrombophilia.	01.05.2021- 20.05.2021

Collaborators and Investigators

• Sponsor: Afyonkarahisar Health Sciences University
• Investigators: Study Director: Serdar Ceylaner, Assoc. Prof., INTERGEN Genetics and Rare Diseases Diagnosis Research & Application Center

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Actual): May 8, 2021
• Study Completion (Anticipated): August 30, 2022

Study Registration Dates

• First Submitted: May 31, 2021
• First Submitted That Met QC Criteria: May 31, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; thrombophilia; genetic factors
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Embolism and Thrombosis; COVID-19; Embolism; Disease Susceptibility; Genetic Predisposition to Disease
• Other Study ID Numbers: 2021-1

Drug and device information, study documents

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