COVID-19, SARS-CoV2 Infection
Conditions
Keywords
Cytokine storm, Mild to moderate COVID-19, Inflammatory cytokines, Dialyzable Leukocyte Extract (DLE), IMMUNEPOTENT-CRP (I-CRP)
Brief summary
In this study, the effects of IMMUNEPOTENT-CRP (I-CRP), a dialyzable leukocyte extract (DLE) derived from bovine spleen cells, on the levels of key inflammatory cytokines in outpatients with COVID-19 were examined. I-CRP has been previously studied for its ability to regulate the immune system in other conditions, such as cancer and sepsis. Based on its potential to reduce harmful inflammation, the study aimed to determine if similar benefits could be observed in COVID-19 outpatients.
Detailed description
Outpatients with mild to moderate COVID-19 symptoms and a confirmed SARS-CoV-2 infection were enrolled. These patients were randomly assigned to receive either IMMUNEPOTENT-CRP (I-CRP) or a placebo over a 14-day period. The study was double-blind, meaning neither the patients nor the researchers knew who was receiving I-CRP or placebo, ensuring unbiased results. The main objective of the study was to measure changes in the levels of specific cytokines and chemokines in the blood-IL-1β, IL-6, IL-10, TNF-α, IFN-α, IFN-γ, and IL-8-which are key players in the inflammatory response linked to severe COVID-19 cases. High levels of these molecules are associated with worse outcomes and more severe symptoms. Additionally, other markers of inflammation and immune system activity, such as lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hs-CRP), ferritin, and D-dimer, were measured, as these are commonly used to assess the severity of inflammation and risk of complications in COVID-19 patients. Throughout the study, outpatients were regularly monitored for symptoms, and their vital signs-such as oxygen levels and body temperature-were checked during home visits. Blood samples were collected at different intervals to measure cytokine levels and the other included inflammatory markers. Patients were also tested four times for the presence of the virus to determine their infection status during the follow-up period.
Interventions
BIOLOGICALIMMUNEPOTENT-CRP (I-CRP)
IMMUNEPOTENT-CRP (I-CRP), a bovine dialyzable leukocyte extract (DLE) obtained from disrupted spleen cells, is a mixture of low-molecular-weight peptides (\<12 kDa) that exhibit non-specific immunomodulatory properties.
BIOLOGICALPlacebo Comparator
The placebo was prepared from a lyophilized corn starch extract and was provided in an identical appearance and presentation to IMMUNEPOTENT-CRP (I-CRP).
Sponsors
Laboratorio de Inmunologia y Virologia - UANL
Hospital Universitario Dr. Jose E. Gonzalez
Universidad Autonoma de Nuevo Leon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Outpatients Inclusion Criteria: * Laboratory-confirmed SARS-CoV-2 infection (by antigen or RT-qPCR test). * With mild to moderate symptoms of COVID-19. * Aged ≥ 18 years. * Not participating in any other clinical study. * Written informed consent duly signed. Outpatients
Exclusion criteria
* Undergoing any process of primary or secondary immunosuppression. * Any autoimmune disease. * Receiving chemotherapy. * History of lymphoma or any malignancy. * Pregnancy or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cytokine and Chemokine Serum Levels Evaluation | Assessments were performed at baseline (Day 0), and during the intervention period at Day 7 and Day 14. | Serum levels of IL-1β, IL-6, IL-10, TNF-α, IFN-α, IFN-γ, and IL-8 were measured using the Human Cytokine/Chemokine Magnetic Bead Panel (Milliplex, Darmstadt, Germany). Cytokine and chemokine concentrations in the serum are expressed in pg/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| High-Sensitivity C-Reactive Protein (hs-CRP) Levels | Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period. | Serum levels of high-sensitivity C-reactive protein (hs-CRP) were measured using standard biochemistry tests. Reference normal values are 0.0-0.3 mg/dL. |
| Ferritin Levels | Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period. | Serum levels of ferritin were measured using standard biochemistry tests. Reference normal values are 13-150 ng/mL. |
| Lactate Dehydrogenase (LDH) Levels | Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period. | Plasma levels of lactate dehydrogenase (LDH) were measured using standard biochemistry tests. Reference normal values are 230-460 mg/dL. |
| Lymphocyte Subpopulations | Lymphocyte subpopulation counts in whole blood were measured at baseline (Day 0), Day 7, and Day 14 during the administration of I-CRP or placebo. | The percentages (%) of lymphocyte subpopulations in whole blood were determined using the BD Multitest 6-color TBNK reagent kit (BD Biosciences, San Jose, USA) and analyzed with the BD FACSCanto™ flow cytometer (BD Biosciences). |
| SARS-CoV-2 Infection Status Evaluation | SARS-CoV-2 infection status was evaluated at baseline (Day 0), Day 7, Day 14, and Day 30 during outpatient follow-up. | Nasopharyngeal/oropharyngeal (NP/OP) flocked swabs collected in 3-5 mL of viral transport medium (VTM) were used to determine SARS-CoV-2 infection status via RT-qPCR. The 2019-nCoV CDC EUA Kit (IDT, Coralville, USA) primers and probe set were used for the assay. RT-qPCR results with a sigmoidal amplification curve and a cycle threshold (Ct) value of ≤37 were considered positive for SARS-CoV-2, while Ct values of 38 and above were considered negative. |
| D-Dimer Levels | Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period. | Plasma levels of D-dimer were measured using standard biochemistry tests. Reference normal values are 0.0-0.5 μg/mL. |
Countries
Mexico
Outcome results
None listed