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Embolism in COVID-19 Positive Patients

Conditions
COVID-19 Pneumonia
Embolism
Genetic Predisposition
Registration Number
NCT04910360
Lead Sponsor
Afyonkarahisar Health Sciences University
Brief Summary

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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
50
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Changes in allelic frequencies in predetermined loci which are known to be related with thrombosis15.03.2021- 30.04.2021

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.

An increase in thrombophilia cases in the study group01.05.2021- 20.05.2021

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

INTERGEN Genetics and Rare Diseases Diagnosis Research & Application Center

🇹🇷

Ankara, Cankaya, Turkey

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