Patients who are ill with COVID-19 may benefit from receiving convalescent plasma infusions containing antibodies from donors who have recovered from the disease and are proven to no longer be infected. Given the current public health emergency due to COVID-19, the FDA has recently fast-tracked the use of convalescent plasma. The purpose for this study is to assess if convalescent plasma collected from donors previously infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can provide clinical benefit to those acutely ill with the virus and to evaluate if such treatment is safe. There will be two arms in the interventional study, where subjects will either be treated with convalescent plasma or fresh frozen plasma in a randomized and blinded manner. As an additional comparison, the clinical course of subjects enrolled during the period of the study who do not receive an alternative treatment for COVID-19 will be assessed.
Study Design and Procedures - Comparison group (no-treatment control)
1. Subjects will be identified by reviewing a REDCap database containing the list of all
patients at the University of Illinois at Chicago Hospital (UIC) who were tested for
COVID-19. Using these data, the investigators will identify those subjects who are >40
years old, were admitted to the hospital during the period of the study, otherwise met
all of the inclusion and exclusion criteria for the infusion arm of the study but were
not enrolled and did not receive any medications for treatment of COVID-19 (were treated
with only supportive care).
2. Clinical data from the hospital admissions of these subjects will be entered into a
REDCap database. The same clinical information captured for subjects who underwent
transfusion (vital signs, oxygen status, etc.) will be entered into this database.
Study Design and Procedures - Intervention arms Screening Visit
1. Patients admitted to UIC Hospital and meeting the inclusion criteria will be enrolled
after documentation of informed consent.
2. Enrolled subjects will answer a symptom screen, undergo a physical exam, and have
clinical data extracted from their chart (including medical history, demographic
information, vital signs and documentation of oxygen requirement).
3. Women of childbearing age will be asked if there is a chance that they might be
pregnant, if they are currently breastfeeding, and if they are planning to become
pregnant.
4. Blood will be drawn for a Complete Blood Count (CBC) and blood type and screen, and a
sample of blood will be stored for research purposes.
5. Nasopharyngeal and/or oropharyngeal swabs will be collected for Reverse
Transcriptase-Polymerase Chain Reaction (RT-PCR) testing.
6. A study investigator will ask the patient's primary team if they are planning on
treating the patient with Remdesivir. If the patient qualifies for this medication, the
study investigator will monitor the patient's chart and work with the patient's nurse to
ensure that the first convalescent plasma infusion and first dose of Remdesivir are
given within 24 hours of each other.
Study Design and Procedures - Transfusion Visits (Study days 0 and 1) Note - the first
transfusion visit may be done on the same day as the screening visit if time permits,
otherwise it will be done the following day. Items 1 and 2 will only be performed for the
first transfusion visit if the visit occurs the day after the screening visit.
1. The patient's clinical status, oxygen requirement, vital signs, and physical exam will
be extracted from their clinical chart. Extracted information will include:
1. imaging: chest X-ray or chest CT results
2. labs: CBC with differential, C-Reactive Protein (CRP), alanine aminotransferase
(ALT), aspartate aminotransferase (AST), total bilirubin, creatinine.
3. Demographic and medical information: history of present infection (length of
symptoms prior to presentation, etc.)
2. Participants will be asked a symptom questionnaire.
3. Randomization to convalescent plasma or fresh frozen plasma will be 1:1. Randomization
will be conducted by a physician not involved in the study and using pre-prepared lists
with random permuted blocks of varying sizes. This physician will hand-deliver an order
sheet for either convalescent or fresh frozen plasma to the blood bank (this way no
orders that could potentially unblind study personnel will be in participants' charts).
4. The blood bank technical staff will select either two compatible blood-type
non-therapeutic units of plasma or two compatible units of convalescent plasma,
depending on which group the patient has been randomized to.
5. If the blood bank does not have any product of that patient's blood type, investigators
will not be able to have the subject complete the remainder of the study. However, the
investigators will keep the information about the participant's blood type in the study
database. Then, in the event that plasma of the appropriate blood type is obtained,
study investigators may contact participants to find out if they are still interested in
being part of the study.
6. The blood product will be delivered to the floor and the participant's nurse will infuse
and document plasma administration following UIC Hospital policy "TX 5.03." Study
subjects will receive 1 unit of plasma the first day, with the second unit being given
the next day.
7. Once the blood product has been hung, the patient's nurse will place it in a bag that
will prevent the patient or physician's taking care of the patient from seeing whether
the unit is regular frozen plasma or convalescent plasma. The nurse will be under
instructions not to convey information about which type of plasma was used to the study
team.
8. The nurse will be instructed to stop the transfusion while a small sample of plasma
remains in the bag. The bag will then be sent back to the blood bank (this is usual
protocol for blood products), and remaining plasma will be emptied into a storage
container, labeled with the patient's study identification number, and frozen for later
use for research purposes.
9. If a transfusion reaction occurs the transfusion will be stopped and reported to the
blood bank as stated in UIC Hospital policy "TX 5.03."
Study Design and Procedures - Post-infusion monitoring
1. Post-transfusion clinical data will be collected from electronic medical record daily
for days 2-8 following the first transfusion (or until the participant is discharged if
they are discharged prior to 8 days following transfusion). This information includes:
1. vital signs: temperature, blood pressure, respiratory rate, pulse
2. symptoms: cough, dyspnea, shortness of breath
3. oxygenation: oxygen saturation, supplemental oxygen requirement, supplemental
oxygen method (e.g., ventilator, nasal canula, prone positioning, etc.)
4. imaging: chest X-ray or chest CT results
5. labs: CBC with differential, CRP, ALT, AST, total bilirubin, creatinine (and
whether or not the patient has required renal support)
6. medications: antibiotics and anti-viral medications, neuromuscular blocking agents,
vasopressors
7. location: intensive care unit, discharged, regular hospital bed
2. The participant will have a swab sample for SARS-CoV-2 RT-PCR collected daily for days
2-8 following the first transfusion (or as many days as they are admitted if they are
discharged prior to 8 days following the first transfusion) and on day 14 following
plasma infusion.
Participants will also have blood drawn on days 2, 4, and 8 following the first plasma
infusion for measurement of antibody titers to SARS-CoV-2 (if they are discharged prior
to day 4 or 8 they will not undergo that day's blood draw).
3. If the patient is discharged prior to 14-days following infusion of plasma, they will be
asked to return to Project Wish on day 14 post- infusion of plasma for a blood draw (for
antibody titers), a nasopharyngeal and/or oropharyngeal swab (for RT-PCR testing) and to
answer a short symptom questionnaire.
4. The patient will be contacted by telephone (if discharged) at 28-days following plasma
infusion and will be asked a symptom questionnaire. If they remain in the hospital at
this time point, they will be asked this questionnaire (if capable) and will have
information regarding their clinical condition extracted from their chart.
Biological: Convalescent plasma
This study will use convalescent plasma collected from those who have previously had COVID-19 and have been shown to have cleared the infection and made antibodies against the virus.
Other Name: Fresh Frozen Plasma
Biological: Placebo
The placebo arm of this study will use fresh frozen plasma that presumably does not contain antibodies against COVID-19.
Other Name: Fresh Frozen Plasma
Inclusion Criteria:
- Patients 40 years-old and over who are admitted to the University of Illinois Hospital
(UIC) due to COVID-19
- Positive oropharyngeal and/or nasopharyngeal swab test for SARS-CoV-2 by RT-PCR within
the preceding 72 hours (performed by University of Illinois Hospital Laboratories or,
if performed elsewhere, documented in the patient's UIC medical record)
- Symptomatic infection with any of the following: fever, cough, dyspnea, or tachypnea >
22 breaths/min
- Need for supplemental oxygen, between 1-5 liters/minute by nasal canula, to maintain
O2 saturations >92%
- Consents to comply with all protocol requirements
- Agrees to storage of specimens for future testing
Exclusion Criteria:
- Patients with known Immunoglobulin A deficiency (high risk of severe or fatal
anaphylactic reactions)
- Patients who are on a ventilator
- Patients with past history of severe transfusion reaction including
transfusion-related acute lung injury (TRALI) or anaphylaxis
- Patients with a baseline requirement for supplemental oxygen due to chronic lung
disease or with known history of either moderate-to-severe asthma or emphysema.
- Female subjects who report that they are pregnant or breastfeeding
- Receipt of pooled immunoglobulin in the past 30 days
- Patients must be willing to not take any another alternative experimental treatment
for COVID-19 from the time they undergo enrollment until the 28-day follow-up phone
call
•. Participants who are being treated with Remdesivir and have had their first dose of
Remdesivir greater than 24 hours prior to the time they will receive their first dose
of convalescent plasma
- Patients with severe disease due to COVID-19, as manifested by a need for
vasopressors, and/or diagnosis of Acute Respiratory Distress Syndrome
University of Illinois at Chicago
Chicago, Illinois, United States
Investigator: Jesica A Herrick, MD, MS
Contact: 312-996-1834
Christe5@uic.edu
Investigator: