Effect of Interleukin 6 Receptor Antagonists in SARS-CoV-2 Patients

Study Overview
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Brief Summary
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Investigate the possible effects of interleukin-6 receptor antagonists such as tocilizumab and sarilumab on the levels of IL-6, inflammtory and anti-inflammtory markers and cytokines before and after treatment in critically ill corona virus disease-19 patients. Correlate between IL-6 levels with other inflammatory markers as ferritin and C-reactive protein. investigate the possible changes on the levels of other inflammatory, anti-inflammatory markers and cytokines such as IL-10 and IP-10, before and after treatment.

Detailed Description
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An outbreak of a mutated respiratory virus that belongs to the Coronavirus family was reported in mid-December 2019, in Wuhan, China. The virus was named as severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the disease was named as coronavirus disease-19 (COVID-19) by the WHO. The infection spread pandemically and by the end of October 2021,the number of confirmed cases of COVID-19 reached 244,897,472, including 4,970,435 deaths, reported by WHO. Viral genome was sequenced and published by public health information on 10th of January. COVID-19 uses the same cell entry receptor {Angiotensin converting enzyme II} (ACE2) as SARS-CoV . Recent studies have shown that IL-6 level increased in severe cases of COVID-19. IL-6 is one of the major pro-inflammatory factors that contribute to the formation of cytokine storm.Therefore, the IL-6 monoclonal antibody (mAb) directed COVID-19 therapy has been used in clinical trial in China. The main conclusion they reached was that the treatment with the IL-6 receptor antagonists ( tocilizumab (TCZ), sarilumab, sirukumab, olamkicept and levilimab) improved outcomes, including survival. TCZ is a humanized antibody that blocks both soluble and membrane-bound forms of IL-6 receptor. Sarilumab is a fully human antibody against the IL-6 receptor that binds to both soluble and membrane-bound IL-6 receptors and has the approval of the food and drug administration (FDA) for rheumatoid arthritis (RA) treatment. Additionally, these drugs have been considered for off-label use in the treatment of COVID-19.

Official Title
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Effects of Sarilumab on Interleukin 6 Levels in Critically Ill COVID-19 Patients

Conditions
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Corona Virus Infection

Intervention / Treatment
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* Diagnostic Test: ELISA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: must be critically ill coronavirus disease-19 Exclusion Criteria: patients receiving corticosteroids pregnancy active TB bacterial infection fungal infection co-infection with other hepatitis viruses.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| critically ill COVID-19 patients in ICU<br>critically ill COVID-19 patients who are recommended to receive IL-6R antagonist as tocilizumab at the dosage of 8 mg/kg with a second dose 12 hours after the first dosage, or sarilumab at the dosage of 200 mg subcutaneously or 200 to 800 mg intravenously. | Diagnostic Test: ELISA<br>* collection of blood samples from critically ill COVID-19 patients, then serum samples are collected after centrifugation measuring IL-6, IL-10 and IP-10 by ELISA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| interleukin-6 levels | Measuring the levels of interleukin-6 in serum of patients. | during one year | 
| interleukin-10 levels | measuring the levels of interleukin-10 in serum of patients before and after treatment | during one year | 
| inflammatory markers | measuring the levels of some inflammatory markers in serum patients | during one year | 
| interferon gamma inducible protein-10 levels | measuring the levels of IP-10 in serum of patients before and after treatment | during one year | 
| anti-inflammatory markers | measuring the levels of some anti-inflammatory markers in serum of patients before and after treatment | during one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival | Calculation of the possible correlation between the variation in interleukin-6 levels and different clinical and laboratory parameters including patient's survival and hospital stay. | during one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interleukin-6 receptor antagonists, Corona virus disease, sarilumab, interferon gamma inducible protein-10