Treatment of Severe Coronavirus Disease 2019 (COVID-19) With Convalescent Plasma

Phase 2

Terminated

Brief Summary: The investigators hypothesize that use of convalescent plasma donated from individuals recovered from Coronavirus Disease 2019 (COVID-19) will help expedite recovery of individuals with active, severe COVID-19 infection.

Detailed Description: The purpose of this research study is to see if convalescent plasma is safe and effective for the treatment of patients acutely ill with COVID-19. The researchers want to confirm the right dose levels of immunoglobulins/antibodies (immune proteins) and find out what therapeutic effects plasma donated by recovered individuals has on people severely sick with COVID-19.

Recruitment & Eligibility

Inclusion Criteria

Inclusion Criteria for Convalescent Plasma Donors:

Phase 1

Exclusion Criteria

Exclusion criteria:

Inability to complete or contraindication to donation based on Donor History -
Questionnaire (DHQ), FDA approved standard blood donation form
Hb<13.0 g/dL for males
Hb<12.5 g/dL for females
History of 3 more pregnancies unless HLA antibody testing is performed and deemed acceptable by director of blood donor services (to reduce risks of transfusion Related Acute Lung Injury in recipients). The presence of any transfusion transmitted diseases is based on history or test results from blood sample collected from the donor at time of plasma collection in accordance to standard practice.
Female subjects who are pregnant by self-report.
Receipt of pooled immunoglobulin in past 30 days

PHASE 2: Inclusion Criteria for Recipients of COVID-19 Convalescent Plasma:

Patients in the Inova Health System with confirmed COVID-19 by PCR testing
Age ≥ 13 years
Currently hospitalized with COVID-19 infection with severe or life-threatening clinical syndrome as follows:
Severe COVID-19: (three or more of the following)
- Dyspnea
- Respiratory rate ≥ 30/min
- Blood oxygen saturation (SpO2) ≤ 94% on room air
- Partial pressure of arterial oxygen to fraction of inspired oxygen (P:F) ratio < 300
- Pulmonary infiltrates > 50% of lung parenchyma within 24 to 48 hours
Life-threatening disease is defined as: (one of the following)
- Respiratory failure
- Septic shock, and/or
- Multiple organ dysfunction or failure
Patient must provide informed consent or have health care power of attorney/next of kin provide consent if he/she cannot.

PHASE 2 Exclusion Criteria:

Contraindication to receive plasma as deemed by the treating physician
Severe hypercoagulable state (documented in medical chart or by treating physician assessment)
Absolute IgA deficiency
Prior history of Transfusion Related Acute Lung Injury (TRALI)
Inability to tolerate plasma volume due to severe systolic or diastolic heart failure despite slower infusion and diuretic administration
Positive pregnancy test (HCG)

Arm && Interventions

Group	Intervention	Description
Recipient of COVID-19 Convalescent Plasma (CCP) Transfusion	Convalescent plasma transfusion	Patients hospitalized with COVID-19 infection with severe or life-threatening clinical syndrome and meet eligibility criteria

Primary Outcome Measures

Name	Time	Method
Change is Clinical Status	Time of plasma infusion (day 0) compared to day 7	Change is clinical status as captured by 7-point ordinal scale to include 1. Death 2. Hospitalized, requiring mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen--requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalized, not requiring supplemental oxygen-not requiring ongoing medical care (COVID-19 related or otherwise). 7. Not Hospitalized
Transfusion Related Events Due to Administration of CCP	Within 6 hours of infusion	Number of participants with Transfusion Related Adverse Events

Secondary Outcome Measures

Name	Time	Method
Mortality	From Day of Transfusion (Day 0) to Day 28 post-transfusion for patients who received CCP. Patients who donated CCP were not followed for a defined time period after CCP donation.	All-cause Mortality
Change is Clinical Status	Time of plasma infusion (day 0 prior to first infusion) to days 7,14, 21, and 28	Change in 7-point ordinal scale score from time of plasma infusion (day 0-prior to first infusion) to days 7, 14, 21, and 28. 7 point ordinal scale: 1. Death 2. Hospitalized, requiring mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen--requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalized, not requiring supplemental oxygen-not requiring ongoing medical care (COVID-19 related or otherwise). 7. Not Hospitalized
Change in Mechanical Ventilation Status	Day 0 (date of CCP transfusion) to Day 28	Number of participants who required a change in the mechanical ventilation status
Length of Hospital Stay	Total Index Hospitalization	Total duration of hospital stay which includes from Admission with COVID-19 from admission with COVID-19 symptoms to discharge or death (up to an average of 67 days)
Mechanical Ventilation	Days 7, 14, 21, 28	Number of participants that required mechanical ventilation that were not on mechanical ventilation at that time point.