Clinical trial NCT05104840: A Randomized Study to Determine the Expression of the Furin Protein in Patients With SARS-CoV-2 and Vaccinated Against Coronavirus
Official title: Randomized Study on Determine the Expression of the Furin Protein in Patients With Confirmed COVID-19 Disease (in Various Phases of the Disease), Recovered From SARS-CoV-2 and Vaccinated Against Coronavirus (All Types of Vaccines)
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: COVID-19
SARS-CoV-2
Furin
RGMc Processing
Paired Basic Amino Acid Cleaving Enzyme (PACE)
Lead sponsor: Center Trials & Treatment
Sponsor class: OTHER
Collaborators: name: Oleg Martynenko
First posted: 2021-11-03
Enrollment: 2432
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: * Patients of coronavirus departments of hospitals and clinics of any specialization.
* Hospital patients for COVID-19 treatment.
* Patients with confirmed SARS-CoV-2 and on outpatient treatment.
* Patients with confirmed SARS-CoV-2 and being treated at home under the remote supervision of a physician.

Brief summary: The rapid spread of SARS-CoV-2 (also known as 2019-nCoV and HCoV-19 1), a novel beta coronavirus B lineage (βCoV), has sparked a global coronavirus disease (COVID-19) pandemic. It has been suggested that RRAR, a unique furin-like cleavage site (FCS) in the spike protein (S) that is absent in other B βCoV lines such as SARS-CoV, is responsible for its high infectivity and transmissibility.

Furin is a protein with a special function of a fermentative biocatalyst: which recognizes the degree of maturity of a group of amino acids Functionally, Furin works to renew the body, but it is also a path to the introduction of the SARS-CoV virus into a living human cell, HIV virus, Ebola virus, and others that penetrate a human cell using the Furin protein, sending a conditioned signal from the extracellular matrix, and gives the virus the opportunity to merge the protein of the coronavirus spike and the protein content of the cut cell, which activates the phase of virus replication in the body.

We hypothesize that measuring the quantitative indicators of Furin protein expression in patients (at the onset of the disease) who have recovered from SARS-CoV-2 and vaccinated (with all types of vaccines) against coronavirus can provide an understanding of the molecular-cellular mechanisms of the virus's cellular invasion. This means that it will be possible to find new ways to prevent the fusion of the membranes of infected cells with normal ones (this mechanism allows the virus to spread throughout the body without leaving the affected cells).

Protein identification will be carried out by Enhanced Chemiluminescence (ECL) (the method of enhanced chemiluminescence differs from the method of immunochemical staining using chromogenic substrates by a much greater sensitivity)

Detailed description: The parameters of the Furin protein in the blood of patients with a confirmed diagnosis of COVID-19 on days 4, 8, or 14 after the onset of symptoms of the disease or a positive PCR test will be assessed ( provided they are in a hospital or clinic for inpatient or outpatient treatment).

* Patients will be asked to donate blood for an enzyme-linked immunosorbent assay of levels of specific IgM and IgG to SARS-CoV-2 from the 3rd to the 39th day after the development of COVID-19 (provided they are in a hospital or clinic for inpatient or outpatient treatment)
* Patients will be asked to take a blood test to quantify antibodies (IgG, IgM) to the IgG class coronavirus to the SARS-CoV-2 spike (S) protein and IgM antibodies, to proteins (nucleocapsid (N) and RBD site of the S-protein ) SARS-CoV-2, (ELISA),

The presence of specific antibodies in the blood serum allows you to determine whether the body has met with the COVID-19 virus and whether antibodies have been developed during the contact that recognizes\] this virus when they meet again. ⠀ The primary immune response to antigens new to the body begins with the production of immunoglobulins M (IgM). IgM to COVID-19 appears in the blood about 2-3 weeks after exposure to the virus in the case of asymptomatic COVID-19 and disappears by about 14-16 weeks.

Since the formation of antibodies is due to the individual characteristics of the immune system, the results of selective testing on different test systems in different countries in different ethnic groups should verify the result.

\* The absence of antibodies will not be evidence of the absence of infection, since there is a concept of a "serological window", when the pathogen has already entered the body, the pathological process develops, but antibodies have not yet appeared.

Age data will be taken into account This study does not imply the receipt, storage and processing of personal data.

* In the vaccinated, the level of Furin protein in the blood will be determined after the first and (or) after the second vaccination, as well as after the booster dose on days 10-60-120-240-360 after vaccination.
* In those who have been ill, but not vaccinated with any vaccine against coronavirus, the level of Furin protein in the blood will be determined up to 60 days after receiving a negative PCR test and the absence of clinical signs of the disease.
* In patients with post-COVID conditions (syndrome), or with a severe form of the disease, the indicators will be determined up to day 180 inclusive after receiving a negative PCR test and the absence of acute clinical signs of the disease.
* If the patients have data, the results of genotyping / mutation and coronavirus variant will be taken into account.
* Patients may be offered compensation (financial reward) for taking tests, participating in a survey, and providing data and/or travel expenses for testing.

Eligibility criteria: Inclusion Criteria:

* Any gender
* Age \> 18
* Hospitalized adult male and female patients with Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection
* Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection
* All Confirmed COVID-19 Patients by PCR or highly suspected patients admitted to the chest department's isolation unit during the duration of the study
* Able to understand and provide voluntary informed consent. Informed consent for participation in the study (consent can be oral if written consent cannot be expressed
* Vaccination with any type of SARS-CoV-2 vaccine

Exclusion Criteria:

* Other medical condition other than COVID-19 or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
* Suspected or known active systemic bacterial, viral (except SARS-CoV2 infection) or fungal infections
* Active herpes zoster infection
* Any physical examination findings and/or history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
* Participation in other clinical trials of investigational treatments for COVID-19.

Primary outcomes:
measure: Determination of the level of Furin protein in the blood of patients with confirmed SARS-CoV2 and being treated in a hospital
timeFrame: up to 12 month
measure: Determination of the level of Furin protein in the blood of patients with confirmed SARS-CoV2 and who are on outpatient treatment
timeFrame: up to 12 month
measure: Determination of the level of furin protein in the blood of those vaccinated against SARS-CoV2 after the first and second vaccinations (or after the ones-dose vaccine J&J)
timeFrame: up to 12 month
Secondary outcomes:
measure: determination of the levels of antibodies (IgG, IgM) to the proteins (nucleocapsid (N) and the RBD S-protein site) SARS-CoV-2 in patients with test positive for COVID-19
timeFrame: up to 12 month
measure: determination of the levels of antibodies (IgG, IgM) to the proteins (nucleocapsid (N) and the RBD S-protein site) SARS-CoV-2 in vaccinated against coronavirus disease (randomized sample by type of vaccine)
timeFrame: up to 12 month
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic-Jacksonville
state: Florida
city: Ocala
country: United States
facility: StatMed Ocala
state: Florida
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Seattle
country: United States
facility: Seattle Intstitute of East Asian Medicine
state: Washington
city: New Delhi
country: India
facility: Institute of Liver & Biliary Sciences
state: Delhi
city: Mumbai
country: India
facility: Humsafar Trust
city: New Delhi
country: India
facility: Max Super Speciality Hospital Saket
city: Srinagar
country: India
facility: Sher i Kashmir Institute of Medical Sciences
city: Kyiv
country: Ukraine
facility: State Institution Republican Clinical Hospital
Study officials:
References: