Clinical trial NCT04887142: Predictors of Disease Severity in COVID-19 Patients
Official title: Biochemical, Inflammatory and Genetic Factors in Patients With COVID-19
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Keywords: COVID-19
Inpatients
Risk Factors
Treatment Outcome
Observational Study
Lead sponsor: University of Kragujevac
Sponsor class: OTHER
First posted: 2021-05-14
Enrollment: 1019
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients of both sexes with different socio-demographic and clinical characteristics, who were hospitalized due to COVID-19. The decision on hospitalization and further treatment of patients is at the discretion of the attending physicians. All participants will be prospectively followed during their hospital stay. Patients will be included in the study if they are at least 18 years old and if they give voluntary written consent to participate. Pregnant and breastfeeding women, patients transferred from other hospitals and those who die during the first 24 hours of hospitalization will be excluded. In this study, stratification of participants according to age to those older than 65 years and younger is provided only for the purposes of statistical data processing and analyse.

Brief summary: The primary goal of the VIRIONUM project is to analyze the association of clinical, socio-demographic characteristics of patients and their genetic polymorphism, inflammatory and other biochemical markers with disease progression and death in subjects with COVID-19 disease. The research is an observational, cohort study with nested-case control design, including adult, male and female COVID-19 inpatients. Primary dependent variable will be outcome of disease, defined as discharge from the hospital or death. The outcomes and putative risk factors will be analyzed using binary logistic regressions. The proposed multi- and inter-disciplinary study should provide additional scientific evidence about risk factors for the development of severe forms of the disease and the COVID-19-related death.

Detailed description: Background: Severe acute respiratory syndrome 2 (SARS-CoV-2) is etiological agent of heterogeneous corona-virus disease 19 (COVID-19), which clinical condition range from asymptomatic or mild to critically severe with high odds for fatal outcome. Since the pathophysiological pathways of COVID-19 disease development are not fully elucidated, resulting in repeated changes in treatment plans, there is an unmet need for more research into genetic, biochemical, immunological, and clinical predictive indicators of better outcomes in COVID-19 patients.

Aim: The VIRIONUM project's main aim is to investigate the relation between genetic polymorphisms, inflammatory and other biochemical markers, and disease severity and mortality in COVID-19-infected hospitalized patients.

Method and patients: The observational nested case-control clinical study will be conducted in at least 1019 COVID-19 patients. The genetic polymorphisms (ACE2, IFNL3/4 and TMPRSS2), serum concentration of soluble ACE2 and the pro- and anti-inflammatory cytokines, blood concentration of common inflammatory and other biomarkers, peripheral blood mononuclear leukocyte (PBMC) phenotype, demographic and clinical risk factors will be monitored as independent variables, while the dependent variables will be the outcome of the disease and the severity of the clinical condition. Genotyping will be performed by Real-Time PCR method, and serum concentrations of ACE2 and pro- and anti-inflammatory cytokines by ELISA method, and PBMC phenotype by flow cytometry. The disease severity will be assessed according to WHO criteria.

Expected results: The findings of this clinical study will contribute to understanding of significant genetic, biochemical, and clinical determinants of severity and lethal outcomes in COVID-19 patients, as well as, creation of set of recommendations for individuals at higher risk - future, evidence-based, targeted and individualized approach.

Eligibility criteria: Inclusion Criteria:

* Adult age, 18 years old or more
* Male or female
* Hospitalization for COVID-19 after confirmation by SARS-CoV-2 rapid antigen test or RT-PCR
* Voluntary written consent of the subject to participate

Exclusion Criteria:

* Pregnant and breastfeeding women
* Fatal outcome during the first 24 hours of hospitalization
* Inability to collect the necessary study data
* Declining of the subject to voluntary participate in the study

Primary outcomes:
measure: Number of Participants with Fatal Outcome
timeFrame: Up to 6 weeks from recruitment to hospital discharge or death
Secondary outcomes:
measure: Ordinal Scale for Clinical Improvement
timeFrame: Up to 6 weeks from recruitment to hospital discharge or death
Other outcomes:
Locations:
city: Tirana
country: Albania
facility: Spitali Amerikan
city: Sarajevo
country: Bosnia and Herzegovina
facility: General Hospital "Prim. dr. Abdulah Nakaš"
city: Rijeka
country: Croatia
facility: KBC Rijeka, University of Rijeka
city: Podgorica
country: Montenegro
facility: University of Montenegro, Faculty of Medicine
city: Kragujevac
country: Serbia
facility: Faculty of Medical Sciences, University Clinical Center Kragujevac
state: Srbija
Study officials:
affiliation: Faculty of Medical Sciences
name: Dejan Baskic, MD PHD
role: STUDY_CHAIR
References: