Clinical trial NCT04910360: Embolism in COVID-19 Positive Patients
Official title: Examining the Genetic Predisposition of Individuals Who Aggravated by Embolism in COVID-19 Positive Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19 Pneumonia
Embolism
Genetic Predisposition
Keywords: thrombophilia
genetic factors
COVID-19
Lead sponsor: Afyonkarahisar Health Sciences University
Sponsor class: OTHER
First posted: 2021-06-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in allelic frequencies in predetermined loci which are known to be related with thrombosis
timeFrame: 15.03.2021- 30.04.2021
measure: An increase in thrombophilia cases in the study group
timeFrame: 01.05.2021- 20.05.2021
Secondary outcomes:
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: INTERGEN Genetics and Rare Diseases Diagnosis Research & Application Center
state: Cankaya
Study officials:
affiliation: INTERGEN Genetics and Rare Diseases Diagnosis Research & Application Center
name: Serdar Ceylaner, Assoc. Prof.
role: STUDY_DIRECTOR
References: