This is a prospective study, involving contacting potential plasma donors and the use of their plasma to help fight off infections of those suffering from COVID19 in accordance to collection guidelines for plasma and FDA IND requirement. This study will include up to 240 participants potentially receiving convalescent plasma and up to 1000 potential donors. There are 3 basic arms to the study: mild, moderate and severe/critical severity. All 3 severity groups are eligible for enrollment, but mild severity will not be given plasma unless there is progression. Moderate severity will given up to 1 unit of plasma and severe/critical severity up to 2 units. There is no placebo group, however given the excepted 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…
y-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