This is a prospective study, involving contacting potential plasma donors and the use oftheir plasma to help fight off infections of those suffering from COVID19 in accordanceto collection guidelines for plasma and FDA IND requirement. This study will include upto 240 participants potentially receiving convalescent plasma and up to 1000 potentialdonors.There are 3 basic arms to the study: mild, moderate and severe/critical severity. All 3severity groups are eligible for enrollment, but mild severity will not be given plasmaunless there is progression. Moderate severity will given up to 1 unit of plasma andsevere/critical severity up to 2 units. There is no placebo group, however given theexcepted issues of shortages of plasma, intention to treat will be used for analysis.
Convalescent plasma (here on referred to as plasma) has been used in emergency
life-threatening situations to treat infections for over 100 years. The plasma is donated
by an individual that has recovered from the very same infection that another person is
infected with. This plasma is enriched in the antibodies that recognize and helped the
body's immune system fight off the infection. When transfused from donor to recipient
those antibodies will aid the recipient in fighting off the infection. In recent history
this has been used to fight Ebola. Recently, the Federal Food and Drug Agency (FDA) made
possible expedited Investigational New Drug (IND) process for plasma use in the fight
against COVID19 for emergency and lifesaving uses.
There are several other investigational drugs for treatment of COVID19 such as:
Remdesivir, an antiviral. The off-label use of hydroxychloroquine, Lopinavir/ritonavir,
or Tocilizumab have been authorized. Convalescent plasma mechanism of action helps to
promote health by working with one's own immune system and will not interfere with the
other proposed medications. It also will not weaken the immune system as the
investigational and off label medications have the potential to do. Convalescent plasma
is time honored and although investigational for each use against novel or rare
infections, it is the basis for IgG infusions in the immunodeficient populations.
Currently the use of IgG infusions such as Intravenous IgG (IVIG) is assumed to not have
the right antibodies from donors in the general public. This is secondary to the novel
nature of the COVID19 and the fact that the IVIG available today was collected 6 to 12
months ago from plasma donors; prior to the COVID19's outbreak discovery in China.
It is for that reason that IVIG is not recommended at this time and the FDA has made
special fast-tracking announcements for plasma use for COVID19. Currently, plasma is the
only treatment that has a previous history of success in these novel or rare viral
outbreak situations. It has already been reported to have been associated with survival
of 5 out of 5 participants in a pilot study in China
For the purpose of this study advanced respiratory support will include any measure of
respiratory support above low flow nasal cannula oxygen (2 Liters/minute flow rate).
For the purpose of this study dyspnea will be defined as any shortness of breath that is
not completely relieved with the use of low flow nasal canula oxygen set to 2
Liters/minute flow rate and/or requiring breathing treatments such as but not limited to:
bronchodilators more than every 4 hours to relieve symptoms.
In the event that more than one recipient is identified and plasma is available in less
than the total number of approved recipients, priority will be given to those approved by
the FDA for the IND use of plasma for severe or critical condition. If there still exists
a deficit of plasma, the priority will be given to those on advanced respiratory support
with the most critical settings (if unclear then will be considered a tie); active
pressor treatments; age <1 years of age with days of life, age adjusted for prematurity
as a tie breaker; age >60 with years as a tie breaker; and lastly lottery pull with
potential remaining recipients as the final tie breaker.
Biological: Convalescent Plasma 1 Unit
Each adult recipient will receive 1 units of plasma, each unit will consist of about 200
to 250 mL.
Each pediatric recipient will receive 10mL/kg up to 1 unit of plasma.
Biological: Convalescent Plasma 2 Units
Those that meet severe or critical criteria will be given 2 units if available or 1 unit
if 2 units are not available.
Those that are given 1 unit may receive the second unit (or the remainder of the maximum
pediatric weight calculated amount of plasma up to 1 additional unit) if they progress to
severe or critical condition or if already in severe or critical condition but only
received 1 unit secondary to shortages.
Each pediatric recipient will receive 10mL/kg up to 2 units of plasma.
Other: Standard of Care
Those that meet mild severity will be allowed to enroll in the study, but will not
receive plasma unless there is progression of illness into the moderate/rapid progression
or greater category.
Inclusion Criteria:
- Plasma donation:
1. Prior diagnosis of COVID-19 documented by a laboratory test
1. Abbott RealTime SARS-CoV-2 real-time reverse transcription polymerase
chain reaction (rRT-PCR) test on the Abbott m2000 System (Inpatient WVU
testing)
2. Other testing methods and vendors using FDA approved detection methods of
SARS-CoV-2 under the Emergency Use Authorization (EUA)
2. Complete resolution of symptoms at least 28 days prior to donation
3. Complete resolution of symptoms for at least 14 days with negative repeat
COVID-19 testing approved by the FDA EUA
4. Female donors age 18+ that have never been pregnant or negative for HLA
antibodies
5. Male donors age 18+
6. Negative results for COVID-19 either from one or more nasopharyngeal swab
specimens or by a molecular diagnostic test from blood. A partial list of
available tests can be accessed at
https://www.fda.gov/medical-devices/emergency-situations-medical-device…
ncy-use-authorizations.
7. Defined SARS-CoV-2 neutralizing antibody titers, if testing can be conducted
(e.g., of at least 1:1602, 1:360 up to 1:640 is preferred. In shortage case
1:80 is acceptable)
8. At least or greater than 50kg of weight
- Plasma Recipients:
1. Individuals of any age above 30 days of life, sex, or pregnancy status
suffering from confirmed COVID19 and in rapid progression, severe or critical
condition meeting the FDA IND guidelines.
2. Must have laboratory confirmed COVID19
3. Must have severe or immediately life-threatening COVID19
4. Must provide informed consent/assent
Exclusion Criteria:
- Plasma donation:
1. Individuals that do not meet the requirement from the American Red Cross for
plasma donation or equivalent
2. Individuals plasma that has not passed safety screening after procurement by
the American Red Cross for plasma donation or equivalent
- Plasma Recipients
1. Individuals with COVID19 who are not in clinical concern for rapid progression,
severe or critical condition
2. Individuals who are in critical condition that are not confirmed to have
COVID19
3. Individuals with known Selective IgA Deficiency, that has not been found to be
absent of anti-IgA antibodies
WVU Medicine
Morgantown, West Virginia, United States
Brian Peppers, DO, PhD
304-594-2483
brian.peppers@hsc.wvu.edu
Lisa Giblin Sutton, PharmD
304-293-0928
giblinl@wvumedicine.org
Brian Peppers, DO, PhD, Principal Investigator
WVU Medicine Children's