Experimental Use of Convalescent Plasma of Passive Immunisation In Current COVID-19 Pandemic in Pakistan in 2020 Rationale & Objective: This study would help to gather real-life setting clinical data in local population, ultimately leading to increased evidence based management of the disease condition in the said population. Eligibility: 1. informed consent must have been obtained 2. confirmed COVID-19 cases confirmed by RT-PCR laboratory tests 3. moderately severe or severe life-threatening COVID-19 related features: a) Moderately Severe disease as defined by the following features: i) Shortness of breath, ii) respiratory rate ≥ 30/min, iii) arterial blood oxygen saturation ≤ 92%, iv) and/or lung infiltrates > 25% within 24 to 48 hours 67 b) Severe Life-threatening disease as defined by: i) respiratory failure, ii) shock, and/or § multiple organ dysfunction Exclusion Criteria: Allergy history of plasma, sodium citrate and methylene blue; 2. For patients with history of autoimmune system diseases or selective IgA deficiency, 3. the application of convalescent plasma should be evaluated cautiously by clinicians. 4. Patients having evidence of uncontrolled cytokine release syndrome leading to end-stage multiorgan failure. Methodology: Total sample size is n=2000. A case report form (CRF) will have to be generated for each corona virus patient at baseline and the completion of study endpoint (at the time of discharge and at 4 weeks after experimental treatment modality using convalescent plasma. - A unique identification number will be issued for each patient in this protocol. - This data will be recorded in the national database. Data sources & Analysis: Patient data originating from patient medical record and assessments (mentioned in table below) will be recorded in the study CRF. Safety data (AEs and SAEs) from any time point during the study will be recorded in the study CRF. All analyses will be performed by third party statistician on SPSS. For continuous variables, summary statistics included n (number of observations), mean, standard deviation, median, minimum and maximum values, as well as frequencies and percentages for categorical variables will be presented.
Passive immunization involves the administration of antibodies against a given agent to a
susceptible individual for the purpose of preventing or treating an infectious disease due to
that agent. A general principle of passive antibody therapy is that it is more effective when
used for prophylaxis than for treatment of disease. When used for therapy, antibody is most
effective when administered shortly after the onset of symptoms. The reason for temporal
variation in efficacy is not well understood but could reflect that passive antibody works by
neutralizing the initial inoculums, which is likely to be much smaller than that of
established disease. As an example, passive antibody therapy for pneumococcal pneumonia was
most effective when administered shortly after the onset of symptoms, and there was no
benefit if antibody administration was delayed past the third day of disease.
The therapeutic benefits of convalescent plasma were formally studied in animal models in
early 20th century. It efficacy was first determined in 1916, when 26 poliomyelitis patients
were treated with convalescent plasma from polio survivors. Subsequently, therapeutic and
prophylactic significance was explored in influenza and measles. Transfusion of immune plasma
is a standard treatment modality for various viral hemorrhagic fevers. Its efficacy in
treating Ebola Virus Disease is also well established. Studies have reported reduction viral
load in patients with H1N1 influenza. Of special attention is the meta-analysis, carried out
by Mair-Jenkinset al, concluding effectiveness of passive immunization as a treatment option
for severe viral acute respiratory infections caused by SARS corona virus, influenza A
(H1N1), avian influenza A (H5N1) and Spanish influenza A. Efficacy of convalescent plasma has
been anecdotally reported in SARS-CoV-2 infections.
Other: convalescent plasma
Plasmapheresis, 900 - 1000 mL each time.
Standard apheresis plasma collection protocol using Haemonetics MCS+ intermittent blood flow system or Terumo Optia, Cobe-Spectra, Trima or Fresenius continuous flow system to be used.
Isovolumic saline replacement should be done.
Each donor can donate convalescent plasma again after an interval of every 2 weeks
Inclusion Criteria:
FOR DONORS:
1. Volunteer enrolment (Informed consent will be obtained; Annexures-2A & 2B).
2. All the regulations related to ICH-GCP and Blood Transfusion Authority (BTA) Pakistan
will be followed.
3. Should fulfill all the criteria of a healthy blood donor (with the exception of
history of COVID-19 during last 4-8 weeks.
4. History of COVID-19 during last 4-8 weeks
5. RT-PCR negative for SARS-CoV-2 RNA (carried out on nasopharyngeal or oropharyngeal
specimen)
6. Age cutoff: 18-55years
7. Body weight cut off: >50 kg for men and > 45kg for women
FOR RECIPIENTS:
1. Volunteer enrolment (Informed consent will be obtained; Annexures-3A & 3B).
2. Confirmed COVID-19 cases confirmed by RT-PCR laboratory tests
3. Severe or Critical COVID-19 related features (8):
a. Severe COVID-19, defined by the presence of any of the following features: i.
Shortness of breath ii. Respiratory rate ≥ 30/min, iii. Arterial blood oxygen
saturation ≤ 93%, iv. Lung infiltrates > 50% within 24 to 48 hours b.
CriticalCOVID-19, defined by the presence of any of the following features: i.
Respiratory failure, ii. Shock iii. Multiple organ dysfunction
Exclusion Criteria:
1. Allergy history for plasma, sodium citrate and methylene blue
2. For patients with history of autoimmune system diseases or selective IgA deficiency,
the application of convalescent plasma should be evaluated cautiously by clinicians.
3. Patients having evidence of uncontrolled cytokine release syndrome leading to
end-stage multi organ failure.
National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD)
Karachi, Sindh, Pakistan
Investigator: Dr. Arshi Naz
Contact: 00923232234376
labarshi@yahoo.com
Investigator:
Dr. Arshi Naz, PhD,Diplab
00923232234376
labarshi@yahoo.com
Dr. Neeta Maheshwary, MBBS Mphil
00923208247773
drneeta@hiltonpharma.com
Dr. Tahir Shamsi, FRCP MRCPath, Principal Investigator
National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD)