Convalescent Plasma Therapy in Patients With COVID-19

The rational use of antibodies from the recovered patient's plasma as a natural neutralizing
antibody to the cell-infected virus (plaques). Several expanded use of convalescent plasma
therapy to severe and/or critically ill COVID-19 patients had been done in the US and China.
Investigator reported that 5 patients received convalescent plasma, three patients were
successfully discharged and 2 patients improved.

Based on the previous study, investigators initiate an intervention study with purposes to
produce quality convalescent plasma from the recovered patients and to find an alternative
treatment to improve the clinical outcomes of severe COVID-19 patients.

Investigators research questions are

1. Are the convalescent plasma could neutralize cell-infected virus in vitro?

2. Are those COVID-19 patients who received convalescent plasma will have a better
prognosis and possibly be cured? The Investigator study hypothesis is convalescent
plasma could possibly cure severe (non-critical) COVID-19 patients.

The primary objective of this study is to produce a good quality convalescent plasma from
recovered COVID-19 patient which could neutralize the plaque in vitro and in Vivo. In Vivo
neutralization will be monitored based on the patient's clinical improvement of symptoms,
laboratory, and radiology assessment.

Invitro tests will be done to the recipient plasma before and after convalescent plasma
transfusion. The objective evaluation will be a plaque reduction neutralizing test (PRNT) of
recipient plasma. Donor plasma will be collected by apheresis methods at the Gatot Soebroto
Blood transfusion unit (BTU).

All donors must meet the eligibility criteria and sign an informed consent form. Donor's
plasma will be screened for blood-borne infection pathogens in BTU. Each donor will produce
210 ml of plasma, which 200 ml will be stored in 2 separate bags (each 100 ml) and 3 ml of
plasma will be tested for antibody anti-COVID-19 titer in Biofarma and 3 ml of plasma will be
tested for PRNT in Eijkman Institute. Plasma transfusion will be given to COVID-19 patients
with severe (IIb) and critical conditions. The storage, testing, transfer, and transfusion of
eligible convalescent plasma are the authority of Gatot Soebroto BTU. Investigators enroll
approximately 10 patients consecutively, who will be admitted at Gatot Soebroto hospital.

All recipients will be enrolled consecutively if they met the eligibility criteria. Baseline
demographic characteristics of the included patient are recorded in case report forms.
Clinical and laboratory data will be measured before the plasma transfusion. Pre-transfusion
patients will be put in group 1. Whereas group 2 is the same patient but received the
convalescent plasma.

Transfusions will be given twice in 100 ml bag, during the 1st 4 hours, the acute adverse
event will be monitored. There will be three serial transfusions, on the 1st day, 3rd day,
and 6th day. The clinical, laboratory and radiology parameters will be re-measured after
the14th day and they will be analyzed.

Data analysis will be done after all the measurement is finished and recorded in clinical
report form. Investigators will find the mean difference of ordinal variables between group 1
and group two with the Wilcoxon signed-rank test (alternative to the paired T-test). The
relative risk (risk reduction) of nominal variables will be measured between group 1 and
group 2. Unfortunately, it is impossible to determine the number needed to harm (NNH) in this
research since both groups are depending on each other.

All documents regarding the study will be kept in data form and will be protected with a
password. We will concern about the safety of convalescent plasma by recording all adverse
events after transfusion. To anticipate the risk of AE progression to a severe adverse event
(SAE), all of the AE will be treated as soon as it is found according to the clinical
competence of treating physicians. SAE will be reported in a certain form to sponsor and data
safety monitoring board as soon as possible.

Investigators are all aware of the potential ethical issue regarding this study. The plasma
convalescent is an alternative therapy for COVID-19, and urgently needed because of the
pandemic situation currently happen. Investigators are weighing all potential expected and
theoretical risks and benefits of convalescent plasma transfusion. The potential expected
risk of plasma transfusions is transfusion reaction (immunological or non-immune related) and
transferred unwanted pathogen. The theoretical risk from plasma transfusion of COVID-19
patient is an antibody-dependent enhancement (ADE) mechanism as seen in dengue patients. A
Potential benefit of plasma for the patient is the neutralizing potential of a polyclonal
antibody to cell infected SARS-Cov2. Resulting in faster recovery and improvement of the
disease stages.

All donors will read the informed consent form thoroughly and willingly given their plasma
draw at Gatot Soebroto BTU. The donor could revoke his/her consent at any time before being
transfused, even after the plasma has been processed and stored in BTU. Donor's decision will
not affect his/her future treatment at Gatot Soebroto hospital.

This preliminary study is supposed to provide supporting data and experience of plasma
processing to a larger study in the near future.