SARS-CoV-2 Antibodies Based IVIG Therapy for COVID-19 Patients

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) Antibodies Based Intravenous Immunoglobulin (IVIG) Therapy for Severe and Critically Ill COVID-19 Patients

Severe and critically ill patients will be enrolled in the study (50 patients) after duly filled consent forms. Recipients shall be divided in to 5 groups with 10 patients per group to compare clinical efficacy and safety of patients in clinical phase I/phase II study. Each group shall receive particular single dose of Intravenously administered Immunoglobulins (IVIG) developed from convalescent plasma of recovered COVID-19 individual , an experimental drug along with standard treatment except for control group which will receive standard treatment only.

Passive immunization using intravenous immunoglobulins (IVIG) has been tested for treating previous viral outbreaks and holds the potential to save lives in the current crisis. Recently researchers from China reported satisfactory recovery of critically ill Corona Virus Disease 2019 (COVID 19) patients when high dose intravenous immunoglobulin (IVIG) were administered. Research team at Dow University of Health Sciences has purified immunoglobulin (both SARS-CoV 2 antibodies and existing antibodies) from convalescent plasma of COVID19 individuals and pooled to prepared IVIG formulation to treat severe and critically ill COVID-19 patients. To evaluate safety of the formulation animal (rats) safety trials and survival of all the animals were observed. It is intended to assess safety and efficacy of experimental the IVIG treatment in severe and critically ill COVID 19 patients through phase I/phase II randomized single blinded clinical trial with fifty study participants. FDA outlined criteria for passive immunization using convalescent plasma, which will be used for recruiting participants in the study.

COVID19 ( Corona Virus Disease -2019), SARS-CoV-2 (Severe Acute respiratory syndrome Coronavirus 2), Passive Immunization, Intravenous Immunoglobulin (IVIG), Pooled convalescent Plasma, Critically ill COVID-19 patients, Severe COVID-19 patients, Antibody

Standard Care + Single dose of 0.20 g/Kg anti-COVID-19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Standard Care + Single dose of 0.25 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Standard Care + Single dose of 0.30 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Standard Care + Single dose of 0.35 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Patient groups will receive IVIG prepared from pooled convalescent plasma from recovered COVID-19 patients. This will be administered sequentially and in varying dosages, infused over a period of 12 hours, intravenously.Additionally, all treatment groups will receive same standard care as control group. Standard Care as per hospital protocol, which may include: Airway support, Anti-Viral medication, Antibiotics, Fluid Resuscitation, Hemodynamic Support, Steroids, Painkillers, Anti-Pyretics

All cause mortality of participants will be monitored for 28 days to assess the safety and efficacy of IVIG treatment.

Number of days required for invasive or non-invasive oxygen supply during hospital stay as per oxygen saturation status of patient

Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

Inclusion Criteria: Above 18 years of age Have positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs Admitted in isolation ward and ICU of institutes affiliated with DUHS have severe or critical COVID 19 as judged by the treating physician Consent given by the patient or first degree relative Exclusion Criteria: Pregnancy Previous allergic reaction to immunoglobulin treatment Ig A deficiency Patient requiring 2 inotropic agents to maintain blood pressures Known case of any autoimmune disorder Acute kidney injury or chronic renal failure Known case of thromboembolic disorder Aseptic meningitis

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U.S Food and Drug Administration (FDA) Recommendations for Investigational COVID-19 Convalescent Plasma

https://thehill.com/policy/healthcare/489335-fda-to-allow-plasma-from-coronavirus-survivors-to-be-used-to-treat

http://www.euro.who.int/__data/assets/pdf_file/0011/268787/Use-of-Convalescent-Whole-Blood-or-Plasma-Collected-from-Patients-Recovered-from-Ebola-Virus-Disease-for-Transfusion,-as-an-Empirical-Treatment-during-Outbreaks-Eng.pdf

WHO guidelines for Use of Convalescent Whole Blood or Plasma Collected from Patients Recovered from Ebola Virus Disease for Transfusion, as an Empirical Treatment during Outbreaks