ANTIBODY-LEVEL BASED ANALYSIS OF COVID-19 CONVALESCENT SERUM (ABACCuS)
Phase: PHASE2
Conditions: COVID-19, Severe Acute Respiratory Syndrome (SARS), Coronavirus Infections
Sponsor: Corewell Health East

TITLE:  
ANTIBODY-LEVEL BASED ANALYSIS OF COVID-19 
CONVALESCENT SERUM (ABACCuS) 
 
NCT04432272 
 
Approval date: 08/26/2020 
 
Protocol and Statistical Analysis Plan 

 
 
ABACCuS Protocol 
 
PI: Matthew Sims, MD PhD 
 
Page | 1 
 
PROTOCOL SUMMARY: 
 
Long title: Antibody-level Based Analysis of COVID Convalescent Serum 
 
Short title: ABACCuS 
 
Protocol Date: August 13, 2020 
 
Clinical Phase: Phase 2  
 
Blinding and Randomization: Double-Blinded to Antibody Content of Convalescent 
Plasma, Not Formally Randomized 
 
IND Sponsor: Beaumont Health 
 
Conducted by: Beaumont Health  
Beaumont Hospital, Royal Oak 
Beaumont Hospital, Troy 
Beaumont Hospital, Grosse Pointe 
Beaumont Hospital, Dearborn 
Beaumont Hospital, Taylor 
Beaumont Hospital, Trenton 
Beaumont Hospital, Wayne 
Beaumont Hospital, Farmington Hills 
 
Trial Oversight 
Matthew Sims, MD PhD, Principal Investigator 
Craig Fletcher, MD, Sub-Investigator 
Gabriel Maine, MD, Sub-Investigator 
Peter Milward, MD, Sub-Investigator 
Christopher Carpenter, MD MHSA, Sub-Investigator 
Paul Chittick, MD, Sub-Investigator 
Richard Kennedy, PhD, Sub-Investigator 
Robert Podolsky, PhD, Biostatistician 
Deborah Hasenau, RN, MS, Research Director 
 
 
Beaumont Hospital, Royal Oak – Florian Bukovec, MD, Sub-Investigator 
Beaumont Hospital, Troy – Sachi Gowda, MD, Sub-Investigator 
Beaumont Hospital, Grosse Pointe – Joel Fishbain, MD, Sub-Investigator 
Beaumont Hospital, Dearborn – Cecilia Big, MD, Sub-Investigator 
Beaumont Hospital, Taylor – Neeraja Varanasi, MD, Sub-Investigator 
Beaumont Hospital, Trenton – Faisal Musa, MD, Sub-Investigator 
Beaumont Hospital, Wayne – Mustafa Bohra, MD, Sub-Investigator  
Beaumont Hospital, Farmington Hills – Wiley Fan, DO, Sub-Investigator 
IRB NUMBER: 2020-198
IRB APPROVAL DATE: 08/26/2020

 
 
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PI: Matthew Sims, MD PhD 
 
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L IST OF ABBREVIATIONS 
ADR: Adverse Drug Reaction 
ADE: Antibody Dependent Enhancement of infection  
AE: Adverse Event/Adverse Experience 
CDC: United States Centers for Disease Control and Prevention  
CFR: Code of Federal Regulations 
CLIA: Clinical Laboratory Improvement Amendment of 1988  
COI: Conflict of Interest 
COVID-19: Coronavirus Disease  
CRF: Case Report Form 
DSMB: Data and Safety Monitoring Board  
EMR: Electronic Medical Record 
EUA: Emergency Use Authorization 
FDA: Food and Drug Administration  
GCP: Good Clinical Practice 
HBV: Hepatitis B virus  
HCV: Hepatitis C virus 
HIV: Human immunodeficiency virus  
HTLV: Human T-cell lymphotropic virus  
IB: Investigator’s Brochure 
ICF: Informed Consent (Informed Consent Form)  
ICH: International Conference on Harmonization  
ICU: Intensive Care Unit 
IND: Investigational New Drug Application  
IRB: Institutional review board 
ISBT: International Society of Blood Transfusion  
MERS: Middle East Respiratory Syndrome  
NP: Nasopharyngeal  
PI: Principal Investigator 
PPE: Personal Protective Equipment 
RT-PCR: Reverse Transcriptase Real-Time Polymerase chain reaction  
SAE: Serious adverse event 
SARS: Severe Acute Respiratory Syndrome 
SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2  
TACO: Transfusion-associated circulatory overload 
TRALI: Transfusion-related acute lung injury  
UP: Unanticipated Problem 
 
 
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Sample Size: 500 (300 serious but non-intubated patients, 200 intubated patients) 
Study Population:  
Group A: Hospitalized COVID-19 patients ages ≥18 years with respiratory symptoms, 
requiring >6L of oxygen to maintain O2 saturation >92%. Patient may not require 
intubation, and may be admitted for no longer than 14 days.  
Group B: Hospitalized COVID-19 patients ages ≥18 years requiring intubation. 
Study Duration: May 15, 2020 to December 31, 2022 
Study Design: This phase 2 trial will evaluate the efficacy and safety of SARS-CoV-2 
convalescent plasma as treatment for confirmed COVID-19 respiratory disease (as 
defined in the inclusion criteria). Adults 18 years of age and older may participate. 
Patients may be enrolled in group A within 14 days of admission to the hospital and may 
be enrolled in group B at any time after intubation. A total of 300 eligible subjects with 
significant oxygen requirements and 200 eligible subjects who require intubation will be 
included in the study. They will receive convalescent plasma from either a patient who 
has recovered from COVID-19 or from an asymptomatic carrier with confirmed IgG 
against SARS-CoV-2. Subjects will not be randomized but the amount of anti-SARS-
CoV-2 IgG and IgA in any unit of plasma will not be known when the unit is assigned to 
the patient. This will allow us to examine the relationship between the amount of anti-
SARS-CoV-2 antibody and outcomes. Analysis will be based on measurement of optical 
density of the IgG level in the unit of plasma the patient is randomly supplied by the 
blood bank. While investigators and patients will be aware the patient is receiving a unit 
of COVID-19 convalescent plasma, both the investigators and the patients will be 
blinded to the antibody content of that unit. 
Assessment in all subjects: Given the issues with the pandemic such as limitations on 
PPE, and the need for strict isolation, patient data will be limited to that which is 
acquired from the EPIC EMR (in use at our institution) but not from face to face 
interview with the patient. The data will be supplemented as possible with phone 
interview with the patient or their LAR. Consenting will be e-consent based using 
RedCap with the consent form e-mailed to the patient or the LAR for review prior to the 
actual consent process. Consent will be obtained over the phone and with a witness: 
the consent provider and the witness will both document the consent process within the 
patient’s chart in the EPIC EMR. 
Study Product: COVID-19 convalescent plasma (1 unit; ~300 mL) The product will be 
produced by Verseti Blood Bank (or other acceptable, blood bank licensed to produce 
plasma) using standard screening and safety procedures. The product may be procured 
from patients who have: 1) been symptom free for 14 days and screen negative via NP 
swab or 2) symptom free for at least 28 days or 3) individuals who have never had 
symptoms of COVID-19 but were found to have elevated anti-SARS-CoV-2 IgG by a 
serology test deemed to be of acceptable quality and fitting the current guidance by the 
FDA. Current protocols from Verseti do not screen for antibody level in COVID 
convalescent plasma, but Verseti retains a residual sample for later testing. Any 
emerging FDA guidance will be followed. From each unit, immediately after thawing, 2 
mL will be removed, 1 mL for SARS-CoV-2 IgA and IgG tests and 1 mL to be held at -
80°C for future neutralizing antibody testing. 
 
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1. Background 
1.1 COVID-19: A Major Pandemic Currently Affecting the Entire World 
In late 2019 the first cases of what has come to be named COVID-19 were noted in 
Wuhan China1. COVID-19 is caused by a novel coronavirus now designated SARS 
coronavirus-2 (SARS-CoV-2). As of 5/3/2020, the total number of diagnosed cases of 
COVID-19 worldwide is 3,566,487 with 248,302 deaths and 1,154,550 have been 
documented to have recovered, and in the United States there are 1,188,122 cases, 
68,598 deaths, and 178,263 recovered2. Michigan as a state has been 
disproportionately impacted, at one point ranked third highest number of cases, though 
due to stay at home orders and other mitigation strategies it has more recently fallen to 
seventh. It remains third highest for deaths due to COVID-19, and it has the highest 
percentage of cases leading to mortality in the US. As of 5/3/1010 in Michigan there are 
currently 43,754 cases, 4,049 deaths, and recovered is not currently available2. The first 
death in Michigan was reported from Beaumont, Wayne3. Eighty percent of the cases in 
Michigan fall within the tri-county Detroit metropolitan area which Beaumont Health 
serves.  
The most common presenting symptoms of COVID-19 are fever, cough, and shortness 
of breath4 and the disease presentation ranges from asymptomatic to mild to an 
overwhelming inflammatory response leading to acute respiratory distress syndrome 
(ARDS) and cytokine release syndrome and ultimately death. The actual mortality of the 
disease is currently unknown but estimates from China suggest a mortality rate of 3.6% 
(95% CI 3.5–3.7)5. In the United States mortality estimates to date indicate that fatality 
was highest in persons aged ≥85, ranging from 10% to 27%, followed by 3% to 11% 
among persons aged 65–84 years, 1% to 3% among persons aged 55-64 years, <1% 
among persons aged 20–54 years, and no fatalities among persons aged ≤19 years6. 
The overall mortality rate ~1.5% which varies day to day (0.8%-2.6% depending on the 
day it is calculated)7. Importantly current mortality numbers for the United States are 
based on a time when the health care system was not overwhelmed. When analyzing 
the mortality of COVID-19 in Italy, a country whose health care system can no longer 
handle the patient load caused by this disease, the mortality is currently estimated at 
9.3%2.  
Those at high risk for progression to severe illness include people over the age of 65, 
people who live in a long term care facility, people with chronic lung disease, people 
with heart disease, immunocompromised patients, people who are obese (BMI≥40), and 
people with other chronic medical conditions such as diabetes, renal failure, and liver 
disease8.  At Beaumont Health we have noted a trend that severe cases tend to be 
male, African American, with diabetes and hypertension (unpublished data). 
1.2 Current Treatment of COVID-19 
There is currently a single treatment approved by the FDA under emergency use 
authorization, remdesivir9. Remdesivir is an experimental medication developed for the 
treatment of Ebola virus and active against RNA viruses including COVID10. Remdesivir 
was studied in an NIH sponsored clinical trial in COVID-19 and did not show a 
statistically significant reduction in mortality, but did show a decrease in length of the 
disease by 31%11. At this time availability of remdesivir remains low and exactly where it 
best fits in the therapy of COVID-19 remains unclear. 
 
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There 
have 
been 
numerous 
other 
approaches 
to 
therapy 
tried 
including 
hydroxychloroquine and azithromycin based in part on the study of Gautret et al12 which 
revealed promising outcomes that were unable to be duplicated by Molina et al13. Other 
studies of hydroxychloroquine in more severely ill COVID-19 patients failed to show a 
significant benefit 14-16 though it remains to be seen if it is useful early in the course of 
the disease to prevent progression or as prophylaxis. Lopinavir-ritonavir is a repurposed 
HIV protease inhibitor which showed good activity against SARS17 but has failed to 
show activity against COVID-1918.  There are numerous other compounds in research 
studies, but none have yet shown any benefit19.  
1.3 Convalescent Plasma as a Therapy for Infectious Diseases 
It is not clear how long convalescent plasma therapy has been used to treat infectious 
diseases but the first protocolized use was in the 1890s as a means to treat 
Diphtheria20. The use continued in the 20th century as a means to treat Scarlet Fever 
and Pertussis and was the only means of treating certain infectious diseases prior to the 
widespread availability of antimicrobial therapy in the 1940s21. The use of convalescent 
plasma to treat viral diseases, including severe respiratory diseases is widespread22 but 
unfortunately the studies are generally poorly controlled for bias23. Notably convalescent 
plasma therapy was used to treat influenza during the Spanish Flu Pandemic of 1918-
1920 with a suggestion of success multiple studies, a meta-analysis of the use of 
convalescent plasma for the Spanish Flu was published in 200624. More recently 
convalescent plasma was used as a potential treatment in the 2013 African Ebola 
epidemic. A small non-randomized study in Sierra Leone revealed a significant increase 
in survival for those treated with convalescent whole blood relative to those who 
received standard treatment25 while other studies were not as positive26. 
1.4 Convalescent Plasma as a Therapy for Coronaviruses 
SARS-CoV-2 is the most recent coronavirus to impact humans, while there are literally 
hundreds, perhaps even thousands of coronaviruses only 7 have been shown to affect 
humans. There are 4 coronaviruses which are causes of the common cold; 229E, NL63, 
OC43, and HKU1. There are 2 other coronaviruses that have been associated with 
epidemics and high mortality, SARS-CoV, the etiologic agent of SARS, and MERS-CoV, 
the etiologic agent of MERS. For both of these epidemics the high mortality and lack of 
effective treatments led to use of convalescent plasma in an attempt to save lives.   
A number of case series of patients treated with convalescent plasma for SARS have 
been published27-32 and were reviewed in a meta-analysis in 2015 by Mair-Jenkins et 
al33. Three of the reports included a single patient each27-29, one report was a series of 3 
health care workers who received plasma30.  
The first study with a reasonable number of patients reported 19 patients who received 
plasma after steroids vs 21 patients who only received steroids31. This study reported 
that no one in the plasma arm died where 5 in the steroid arm died. However the study 
had multiple issues, it was not randomized, the steroid group had significantly higher 
comorbidities, and 9 members of the steroid group crossed over and received plasma. 
They concluded that plasma was associated with a significant decrease in mortality 
(p=0.049) and that receiving plasma after day 16 was associated with a poor clinical 
response (based on the crossover group). The also recognized that this may simply 
have been due to the control group receiving steroids which was later shown to be 
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contra-indicated in SARS.  
The largest case series was 80 patients in Hong Kong who received convalescent 
plasma32. Of the 80 patients, 33 had a good outcome, which was defined as discharge 
by day 22 from onset of the disease, 47 had a poor outcome which was defined as 
death by day 22 from onset of the disease or continued need for hospitalization after 
day 22. In this study the overall mortality rate among the 80 patients was 12.5% 
whereas the overall mortality rate in Hong Kong was 17%. Sub-analysis of the patients 
who received convalescent plasma also noted that those who received convalescent 
plasma before 14 days did better than those who received it after 14 days. 
Both studies involving a larger number of patients noted that there were no adverse 
events associated with receiving convalescent plasma and both studies noted that there 
were better outcomes when plasma was given before 14 or 16 days. The choice to limit 
Group A in this study to patients admitted no longer than 14 days is based on these 
observations. 
While there were clearly attempts to use convalescent plasma for MERS34, there are no 
published cases series and only a single case report documenting a patient treated with 
convalescent plasma who developed TRALI35. Unlike SARS and COVID-19, MERS has 
a very low rate of person to person spread. An analysis of MERS antibody levels in 
patients with MERS or suspected MERS, healthcare workers with confirmed exposure 
to MERS, and household contacts of patients with MERS was performed in 201536. The 
study had numerous issues, including the fact that very few participants had laboratory 
confirmed MERS and the timing of serology testing after infection or exposure was 
highly variable, however it showed very few had developed significant antibody levels 
making the use of convalescent plasma in MERS questionable and raising the concern 
that simply using plasma from patients who recovered from a coronavirus infection may 
not have adequate antibodies for a therapeutic effect. 
1.5 Convalescent Plasma as a Therapy for COVID-19 
To date there have been 6 case series published using COVID-19 convalescent plasma 
as a treatment37-42. In addition, there was a meta-analysis performed of the initial 5 case 
series43. The various case series treated anywhere from 2 to 6 patients and in 5 of the 
reports all patients survived. However, when the patient populations in these studies are 
looked at, even when described as severe, cases often were not actually severe at the 
time they received convalescent plasma all but had been severe earlier in their 
admission38. In fact, one patient in a series was already discharged from the hospital but 
called back in and given a dose of convalescent plasma because they had a positive 
PCR for SARS-CoV-2 despite clinical improvement39.  
In the last case series 21 patients were eligible for plasma but only 6 received it due to 
the limited availability of convalescent plasma and ABO compatibility. The mortality in 
the treatment group was 5/6 and in the control group was 14/15. The patients who 
received convalescent plasma had a higher clearance of the virus (p=0.005) and a 
longer survival period (p=0.029) but no improvement in mortality42. 
It is important to note that in the various case series, with few exceptions there was no 
measurement of anti-SARS-CoV-2 antibody in the convalescent plasma and no specific 
protocol under which it was given. The patients were highly heterogeneous, the 
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definition of a unit of plasma by volume varied, and the volume of plasma given varied 
from 200 ml to 2400 ml with no clear reason behind dosing additional units other than 
lack of patient improvement40. 
1.6 Mechanism of Action 
Convalescent antibody therapy involves the administration of plasma from persons 
recovered from an infection to a susceptible or ill individual. It is assumed, the plasma 
contains antibodies against the infectious agent but this has frequently not been 
confirmed in prior studies.  
It is intuitively obvious that if convalescent plasma is efficacious for the treatment of an 
infection that the mechanism of action would be passive antibody therapy where 
antibodies against the pathogen lead to neutralization of the pathogen44. However, other 
mechanisms may be possible, such as antibody dependent cellular cytotoxicity and/or 
phagocytosis45. It has also been suggested that there are multiple ways in which 
convalescent plasma can lead to antibody regulated immunomodulation which in turn 
leads to down regulation of the hyper-inflammatory reaction associated with COVID-
1946. 
One study examining the convalescent plasma from SARS patients found increased 
levels of multiple inflammation inhibitors in the plasma that were completely unrelated to 
the antibodies present47. 
Given that many of the patients who recovered from COVID-19 in the published case 
series were intubated long past the time when it was likely active virus was still present 
to be neutralized48 and long past the time when they should have developed their own 
neutralizing antibodies49, there may be an as yet undefined mechanism to the activity of 
convalescent plasma. 
 
 
 
 
 
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2. Research Design  
2.1 Objectives 
Group A Primary Efficacy Objective: Evaluate the association between efficacy of 
treatment with COVID-19 convalescent plasma and the amount of Anti-SARS-CoV-2-
spike protein IgG as assayed by the EUROIMMUN Anti-SARS-CoV-2 assay. 
 
Group A Primary Efficacy Endpoint: Avoidance of intubation at 28 days. 
Group A Secondary Efficacy Endpoints: 
1. 
Final outcome on a 7-point ordinal scale  
2. 
Cardio-circulatory arrest (at any time) 
3. 
Renal failure, as measured by RIFLE criteria 
4. 
Liver failure, as measured by elevation of ALT and AST to 5x the upper limit of 
normal or significant worsening of current liver failure with rise in transaminases 
of >25% 
5. 
Evidence of cytokine storm based on measurement of inflammatory markers 
6. 
Type and duration of respiratory support  
7. 
Requirement of pressor support  
8. 
ICU mortality  
9. 
ICU length of stay 
10. In hospital mortality 
11. 28-day mortality 
12. Length of stay 
13. Ventilator-free days 
14. Readmission rate 
15. Patient level of anti-SARS-CoV-2 IgG at the following times: prior to 
transfusion, 1-hour post-transfusion, 24 hours post-transfusion, 72 hours post-
transfusion, 7 days post-transfusion, every 7 days until discharge, day of 
discharge.  
16. Evaluate the rates, levels (based on CT values) and duration of SARS-CoV-2 
RNA in nasopharyngeal swabs using RT-PCR amongst the anti-SARS-CoV-2 
convalescent plasma at the following times: prior to transfusion, 24 hours post-
transfusion, 72 hours post-transfusion, 7 days post-transfusion, and 14 days 
post-transfusion.  
Group A Investigational Efficacy Objectives: 
1. 
Evaluate the efficacy of treatment with COVID-19 convalescent plasma in 
relation to the amount of Anti-SARS-CoV-2-spike protein IgA as assayed by the 
EUROIMMUN Anti-SARS-CoV-2 assay. 
2. 
Evaluate the efficacy of treatment with COVID-19 convalescent plasma in 
relation to the amount of both Anti-SARS-CoV-2-spike protein IgG and IgA as 
assayed by the EUROIMMUN Anti-SARS-CoV-2 assay. 
 
All primary and secondary efficacy endpoints for the study will be re-evaluated based on 
levels of IgA for investigational objective #1 and based on combined levels of IgG and 
IgA for investigational objective #2 
 
 
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Group B Primary Efficacy Objective: Evaluate the association between efficacy of 
treatment with COVID-19 convalescent plasma in relation to the amount of Anti-SARS-
CoV-2-spike protein IgG as assayed by the EUROIMMUN Anti-SARS-CoV-2 assay. 
 
Group B Primary Efficacy Endpoint: Mortality at 28 days. 
Group B Secondary Efficacy Endpoints: 
1. 
Final outcome on a 7-point ordinal scale  
2. 
Cardio-circulatory arrest (at any time) 
3. 
Renal failure, as measured by RIFLE criteria 
4. 
Liver failure, as measured by elevation of ALT and AST to 5x the upper limit of 
normal or significant worsening of current liver failure with rise in transaminases 
of >25% 
5. 
Evidence of cytokine storm based on measurement of inflammatory markers 
6. 
Type and duration of respiratory support  
7. 
Requirement of pressor support  
8. 
ICU mortality  
9. 
ICU length of stay 
10. In hospital mortality 
11. Length of stay 
12. Days from transfusion till end of ventilator support in survivors 
13. Ventilator-free days 
14. Readmission rate 
15. Patient level of anti-SARS-CoV-2 IgG at the following times: prior to 
transfusion, 1-hour post-transfusion, 24 hours post-transfusion, 72 hours post-
transfusion, 7 days post-transfusion, every 7 days until discharge, day of 
discharge.  
16. Evaluate the rates, levels (based on CT values) and duration of SARS-CoV-2 
RNA in nasopharyngeal swabs using RT-PCR amongst the anti-SARS-CoV-2 
convalescent plasma at the following times: prior to transfusion, 24 hours post-
transfusion, 72 hours post-transfusion, 7 days post-transfusion, and 14 days 
post-transfusion.  
Group B Investigational Efficacy Objectives: 
1. Evaluate the efficacy of treatment with COVID-19 convalescent plasma in 
relation to the amount of Anti-SARS-CoV-2-spike protein IgA as assayed by the 
EUROIMMUN Anti-SARS-CoV-2 assay. 
2. Evaluate the efficacy of treatment with COVID-19 convalescent plasma in 
relation to the amount of both Anti-SARS-CoV-2-spike protein IgG and IgA as 
assayed by the EUROIMMUN Anti-SARS-CoV-2 assay. 
 
All primary and secondary efficacy endpoints for Group B will be re-evaluated based on 
levels of IgA for investigational objective #1 and based on combined levels of IgG and 
IgA for investigational objective #2 
 
 
 
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Primary Safety Objective for Group A and B: Evaluate the safety of treatment with 
COVID-19 convalescent plasma in relation to the amount of Anti-SARS-CoV-2-spike 
protein IgG as assayed by the EUROIMMUN Anti-SARS-CoV-2 assay. 
Primary Safety Endpoints: 
1. Rapid deterioration of respiratory or clinical status on transfusion of COVID-19 
convalescent plasma 
2. Development of increased cytokine storm activity within 48 hours of receiving a 
unit of COVID convalescent plasma. 
Secondary Objectives: 
1. Cumulative incidence of serious adverse events during the study period: 
transfusion reaction (fever, rash), transfusion-related acute lung injury (TRALI), 
transfusion-associated circulatory overload (TACO), and transfusion-related 
infection. 
Investigational Safety Objectives: 
1. Evaluate the safety of treatment with COVID-19 convalescent plasma in relation 
to the amount of Anti-SARS-CoV-2-spike protein IgA as assayed by the 
EUROIMMUN Anti-SARS-CoV-2 assay. 
2. Evaluate the safety of treatment with COVID-19 convalescent plasma in relation 
to the amount of Anti-SARS-CoV-2-spike protein IgG and IgA as assayed by the 
EUROIMMUN Anti-SARS-CoV-2 assay. 
All primary and secondary safety endpoints for the study will be re-evaluated based on 
levels of IgA for investigational objective #1 and based on combined levels of IgG and 
IgA for investigational objective #2 
2.2 Data collection 
The following data points will be gathered for all patients in the study while inpatient. 
Patients discharged prior to 28 days will receive a phone call to determine their 28 day 
outcome and patients enrolled in the study will be monitored for 90 days from discharge 
to determine if there is a readmission and the reason for the readmission. 
COVID-19 Presentation: Collected on enrollment, see form on page 30. 
Demographics: Collected on enrollment, see form on page 31. 
Medical History: Collected on enrollment, see form on page 31. 
Concomitant Medications: Collected on enrollment, see form on page 31. 
Vital Signs: Collected daily from enrollment to discharge, see form on pages 30 and 32. 
Laboratory Values: Collected daily from enrollment to discharge, patient is required to 
have a CBC with differential, a CMP, a ferritin and a CRP. On enrollment and weekly 
the patient must have an IL-6, D-Dimer, procalcitonin, LDH, fibrinogen, ESR, and 
CK. IL-6 and LDH, other laboratory values will be recorded when obtained through 
standard of care. See form on page 32. 
Clinical Status: Collected daily from enrollment to discharge, see form on page 32. 
Medications: Collected daily from enrollment to discharge, see form on page 33. 
Serology Values: Collected per schedule, see form on pages 34 and 35. 
PCR Values: Collected per schedule, see form on page 36 
Safety Data: Collected for first 24 hours after transfusion, see form on page 37. 
Outcomes: Collected at discharge or death, see form on pages 38 and 39. 
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2.3 Study population 
Inclusion Criteria for Enrollment 
1. Subjects must be 18 years of age or older. 
2. Hospitalized with confirmed COVID-19 infection via COVID-19 SARS-CoV-2 RT-
PCR testing. 
3. Symptoms consistent with COVID-19 infection (fever, acute onset cough, 
shortness of breath) at time of screening. 
4. Patient requires >6L NC O2 (Group A) or intubated (Group B). 
5. Patient (or their representative) is willing and able to provide written informed 
consent and comply with all protocol requirements. 
Exclusion Criteria 
1. Female subjects with positive pregnancy test, breastfeeding, or planning to 
become pregnant or breastfeed during the study period. 
2. Receipt of pooled immunoglobulin in past 30 days. 
3. Contraindication to transfusion or history of prior reactions to transfusion blood 
products. 
4. Patients currently undergoing cancer treatment or those who are presently 
immunocompromised. 
5. Patient who in the opinion of the investigator will not be a good study candidate. 
 
 
 
 
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2.4 Schedule of events 
Study Period 
Screening 
Baseline 
Treatment 
Follow Upa 
Day 
-1 to 0 
0 
0 
D 
1 
3 
7 
14 
21 
28 
Eligibility 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Demographics and 
medical history form 
X 
 
 
 
 
 
 
 
 
 
Initial data collection 
form 
X 
 
 
 
 
 
 
 
 
 
Type and Screen 
X 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
X 
 
 
 
 
 
 
 
 
 
Study Procedures 
 
Plasma transfusion 
 
 
X 
 
 
 
 
 
 
 
Vital signs 
 
 
Xb 
 
 
 
 
 
 
 
Physical examc 
X 
 
Xd 
 
X 
 
X 
 
 
 
Daily vital signs, clinical 
and laboratory values 
form 
 
 
 
X 
 
 
 
 
 
 
Daily medications form 
 
 
 
X 
 
 
 
 
 
 
Adverse event 
monitoring 
 
X 
X 
X 
 
 
 
 
 
 
Serology collection form 
 
X 
X 
 
X 
X 
X 
X 
X 
Xe 
Outcome form 
 
 
 
 
 
 
 
 
 
Xf 
Laboratory Testsg 
 
CBC with differential 
 
X 
 
X 
 
 
 
 
 
 
CMP 
 
X 
 
X 
 
 
 
 
 
 
Ferritin 
 
X 
 
X 
 
 
 
 
 
 
Fibrinogen 
 
X 
 
 
 
 
X 
X 
X 
X 
CRP 
 
X 
 
X 
 
 
X 
X 
X 
X 
ESR 
 
X 
 
 
 
 
X 
X 
X 
X 
Creatine Kinase 
 
X 
 
 
 
 
X 
X 
X 
X 
D-Dimer 
 
X 
 
 
 
 
X 
X 
X 
X 
LDH 
 
X 
 
 
 
 
X 
X 
X 
X 
Interleukin-6 
 
X 
 
 
 
 
X 
X 
X 
X 
Triglycerides 
 
X 
 
 
 
 
X 
X 
X 
X 
Procalcitonin 
 
X 
 
 
 
 
X 
X 
X 
X 
Anti-SARS-CoV-2 IgA 
 
 
Xh 
 
X 
X 
X 
X 
X 
Xi 
Anti-SARS-CoV-2 IgG 
 
 
Xh 
 
X 
X 
X 
X 
X 
Xi 
SARS-CoV-2 RT PCR 
 
 
Xj 
 
X 
X 
X 
X 
 
 
a – Column D are obtained daily, day 1 and 3 are obtained 24 hours (+/- 1 hour) from transfusion end, day 7, 14, 21, 
and 28 are obtained any time on that calendar day. 
b – Standard vital signs for transfusion of blood products will be performed. 
c – Given the issues with isolation and PPE, the exam of the attending physician’s team or the pulmonary critical care 
team can be used. 
d – Only if needed due to acute reaction. 
e – After 28 days will be collected every 7 days +/- 1 day till discharge. 
f – Outcome form to be filled out on final day of admission if prior to 28 days or at 28 days, after 28 days a second 
outcome form to be filled out on final day of admission, readmission will be tracked for 90 days. 
g – All laboratory tests from this list which are obtained as standard of care will be tracked, baseline labs within 24 
hours are acceptable and do not need to be reordered. 
h – To be drawn within 1 hour prior to transfusion and 1 hour post-transfusion completion (no earlier than 1 hour but 
up to 75 min post transfusion). 
i – After day 28 this will be drawn every 7 days +/- 1 day while participant remains hospitalized. 
j – To be obtained within 1 hour prior to transfusion. 
 
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2.5 Treatment 
All study participants will receive 1 unit of the study product. There is no re-dosing of the 
product within this study. There is no formal randomization, but both the patient and the 
study team will be blinded to the amount of anti-SARS-CoV-2 antibodies found in the 
unit of plasma assigned to the participant. The blind will be maintained until study 
closure and formal data analysis. 
2.6 Rationale for Dose 
Review of the literature using COVID-19 convalescent plasma reveals that there is 
currently no standard dose or schedule for giving convalescent plasma. In addition there 
is currently no standard assay for antibody level performed on plasma in the United 
States and there is no way to guarantee access to more than one unit of plasma at a 
time or guarantee that if more than one unit were available they would be comparable in 
antibody content. As such the dose was chosen via the pragmatic approach of using a 
single unit of plasma and stratifying the results by the serological assay of that unit. 
2.7 Study drug administration 
1. Plasma will be administered at an infusion rate ≤ 500 mL/hour per standards 
determined by the blood bank.  
2. Pretreatment 
to 
minimize 
transfusion 
reactions 
(e.g. 
acetaminophen, 
diphenhydramine) may be given per investigator and clinical care team 
discretion. 
3. If an AE develops during infusion, the infusion may be slowed or stopped as per 
investigator’s decision. 
4. Most reactions to plasma are relatively minor and the infusion can generally be 
continued. Infusion site burning and non-allergic systemic effects can generally 
be managed with slowing of the infusion. Infusion can generally be continued in 
case of itching or hives after pausing the transfusion, administering 
antihistamines, and observing the patient for worsening. 
5. Severe allergic reactions, such as bronchospasm and hypotension, may require 
discontinuation of the infusion. 
2.8 Subject Withdrawal 
Taking part in this research study is completely voluntary. A participant may choose 
not to take part or to stop being in the study (withdraw) at any time without penalty or 
loss of benefits to which they are otherwise entitled, and without jeopardizing their 
medical care.  
If a participant (or their LAR) decides to withdraw from the study they will need to 
notify the study PI, in writing, of their decision to stop taking part in the study. 
Detailed directions regarding this will be included in the consent and authorization 
form for the study.  
Participation in this study may be stopped by the study PI or the site PI without the 
participant’s consent for an appropriate reason, which will be explained to the 
participant or their LAR. Examples include: 
• The study medication or procedures appear to be medically harmful to the 
participant.  
• The participant fails to follow directions for the study.  
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• It is discovered the participant does not meet the study requirements.  
• The study is canceled.  
• It is determined to be in the participant’s best interest.  
Subjects who withdraw or are removed from the study will not be replaced. 
Discontinuation of the study: The IND holder, Beaumont Health, the FDA, the IRB, and 
the DSMB all have the right to terminate this study at any time. 
 
3. Statistics 
3.1 Data Analysis 
We will summarize all baseline data using means, standard deviations, medians and 
interquartile range for all continuous variables. All data will be examined graphically 
prior to any modeling.  
Primary Outcomes: All analyses of primary outcomes will use a 5% significance level. 
This study will have two primary outcomes: (1) whether a patient needed intubation for 
Group B patients, and (2) 28-day survival for Group B patients. For both outcomes, we 
will use logistic regression models with IgG levels as the primary independent variable. 
We expect that the relationship between outcome and IgG levels will be non-linear since 
there should be a quick increased probability of a “good” outcome once IgG levels are 
sufficiently large, and with this probability of a “good” outcome not increasing much if Ig 
levels become very high. As such, the relationship with IgG levels will be modeled using 
splines. We will use both the Akaike informatic criterion (AIC) and the Schwartz 
Bayesian information criterion (BIC) to select the number of knots to include. Age, 
gender, and race will also be included as covariates. We will conduct a sensitivity 
analysis focused on the estimate and confidence interval for the relative risk in a linear 
model for IgG levels. This sensitivity analysis will add comorbidities singly as covariates. 
While log-binomial models would be preferred to logistic regression models for obtaining 
estimates of relative risk based on model parameters, log-binomial regression models 
are often difficult to fit, especially when including splines. As such, we will estimate local 
relative risks based on the fitted model using numerical derivatives for a given IgG level. 
We will also be able to estimate relative risk of two IgG levels using the same approach.  
We will also consider using a piecewise log-binomial model,  
log(𝑝𝑝) = 𝛽𝛽0 + 𝛽𝛽1𝐼𝐼(𝑥𝑥> 𝑠𝑠), 
where 𝑝𝑝 is the probability of the outcome, 𝛽𝛽0 is the intercept (baseline-probability of the 
outcome), and 𝛽𝛽1 is the coefficient describing the log of the relative risk for having large 
amounts of antibody, the knot 𝑠𝑠 determines the cutoff for characterizing large amounts 
of antibody. We will use Bayesian inference with a binomial likelihood, a beta(0.5,0.5) 
prior for exp(𝛽𝛽0), a weak normal prior for 𝛽𝛽1, and a uniform(0,maximum(IgG/IgA level)) 
prior for the knot, 𝑠𝑠.  
Secondary Outcomes: Analyses of all secondary outcomes will use a 0.3% 
significance level based on the Bonferroni correction for 16 tests. Final outcome 
measured on a 7-point ordinal scale will be analyzed using standard linear regression, 
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although we will also consider proportional odds models should the range of the scale 
actually used be small (i.e., only 3-4 categories appear in the data). We will not use 
splines for the standard linear regression, but will use splines if a proportional odds 
model is fit to the data. We will use the same logistic regression approach as for the 
primary outcomes for all binary secondary outcomes (cardio-circulatory arrest, renal 
failure, liver failure, evidence of cytokine storm, pressor support required, and 
readmission).  
We anticipate a small number of total number of mortality events for Group A. Should 
mortality for Group A be small, we will use Fisher’s exact test based on categorizing the 
unit received by each patient as either low vs. high for amount of Anti-SARS-CoV-2-
spike protein IgG. The cutoff for categorizing units will be based on either median 
amount or based on the cutoff determined by the Bayesian log-binomial piecewise 
model. For Group B, all secondary mortality outcomes will be analyzed the same as for 
the primary outcome. Should the number of events for any specific type of mortality 
(e.g., ICU mortality) prove small, we will use the approach used for analyses of Group 
A.  
We will use a generalized linear model with splines to analyze all duration types of 
variables (duration of respiratory support, ICU length of stay, total length of stay). We 
will consider using normal, log-normal, and gamma distributions, along with appropriate 
links.   
Type of respiratory support will be analyzed using a multinomial regression with splines 
for antibody amount, although we will also consider using Fisher’s exact test by 
categorizing the unit received by each patient as either low vs. high for amount of Anti-
SARS-CoV-2-spike protein IgG.  
We will use either standard linear regression or Poisson regression for ventilator-free 
days, including splines.  
We will use generalized linear mixed models to characterize changes in patient level of 
anti-SARS-CoV-2 IgG, and the rates, levels (based on CT values) and duration of 
SARS-CoV-2 RNA in nasopharyngeal swabs. These models will include time as a fixed 
effect, and will also include the random intercept for subject. We will also consider 
adding other random coefficients based on both AIC and BIC.  
Investigational Outcomes: We will examine the relationship between primary and 
appropriate secondary outcomes with IgA levels as an investigational analysis using the 
same types of models being fit as for IgG levels.  
3.2 Power and sample size 
We determined sample size based on a logistic regression model with a linear 
relationship between outcome and IgG level, and we used simulations to evaluate 
power for different sample sizes since we expect some sort of non-linear relationship. 
We assumed a piecewise model in which the probability of a good outcome increased 
once IgG levels were greater a threshold. Most of our power calculations used a 
threshold of 5 since a larger threshold resulted in slightly greater power. We expect this 
simulation approach to provide an estimate of the minimal power since we use a linear 
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Table 1. Power for detecting an 
increase in 28-day survival when the 
baseline probability is 0.25 and the 
sample size is 200. 
28-day Survival for 
high levels of IgG 
Power 
0.45 
74.4% 
0.50 
87.8% 
0.55 
97.6% 
Table 2. Power for detecting a 
decrease in intubation rate when the 
baseline probability is 0.38 and the 
sample size is 300. 
Intubation Rate for 
high levels of IgG 
Power 
0.23 
60.6% 
0.18 
87.9% 
0.13 
98.3% 
relationship when the relationship is actually not linear.  We assumed the baseline 
probability was 25% for 28-day survival and 38% for intubation rate. We selected a 
sample size of 200 for 28-day survival since this sample size provides excellent power 
(87.8%) for detecting an increase in 28-day survival to 50% (Table 1). We selected a 
sample size of 300 for intubation rate since this sample size provides excellent power 
(87.9%) to detect a decrease in intubation rate to 18% (Table 2). 
 
 
 
 
 
 
 
 
 
 
 
4. Protection of Human Subjects 
The entirety of this study will be approved and monitored by the Beaumont Health 
Institutional Review Board of Record (FWA0002516).  
This research will be conducted as a clinical investigation requiring an IND as per title 
21 of the Code of Federal Regulations, part 312 (21 CFR part 312) and the guidance 
from the FDA given on May 1, 2020 found at https://www.fda.gov/vaccines-blood-
biologics/investigational-new-drug-ind-or-device-exemption-ide-process-
cber/recommendations-investigational-covid-19-convalescent-plasma 
4.1 Risks to the Subjects  
Human Participant Involvement and Characteristics  
Antibody-level Based Analysis of COVID Convalescent Serum, ABACCuS, will be a 
prospective, single-center, double-blinded, study of the effectiveness of COVID-19 
convalescent plasma for the treatment of COVID-19.  
We plan to enroll 500 inpatients from the eight Beaumont Hospitals, 300 of which are 
requiring >6L of oxygen to maintain O2 saturation >92% but are not requiring intubation 
and 200 of which are requiring intubation. All enrolled patients, or their legally 
authorized representative (LAR) must sign an Informed Consent Form (ICF).  
All patients will receive a unit of COVID-19 convalescent plasma but the antibody 
content of the unit will not be known and there will be a double-blind such that neither 
the patient nor the study personnel will know the anti-SARS-CoV-2 antibody levels 
within the plasma. 
During the study, various clinical and demographic data on each patient will be collected 
as detailed in the Research Design section. 
A schedule of events for all patients in the study is included above (Section 2.4). 
Inclusion and exclusion criteria for the study are included above (Section 2.3). 
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No vulnerable populations of children or pregnant women will be recruited to the study. 
Children are exempted due to differing impact of SARS-CoV-2 on the pediatric 
population as compared to that of adults. Pregnant women are exempted due to 
unknown risks to the fetus. Cognitively impaired patients are allowed but will need to be 
consented using an LAR. 
Sources of Materials  
Participants will provide the required blood samples at the indicated time points, as 
described in the Research Strategy, and outlined in the above schedule of events 
(Section 2.4). Additional participant data will be obtained through a chart review within 
Beaumont’s EMR (EPIC) and supplemented where appropriate by patient completion of 
interviews. 
All patients enrolled in the study will be followed daily while inpatient by research 
coordinators who will gather all required data.  
Potential Risks  
Historical and current anecdotal data on use of convalescent plasma suggest its use to 
treat COVID-19 is generally safe. The large number of exposed individuals, in 
combination with the high mortality of COVID-19, particularly in vulnerable persons, 
strongly suggests that the potential benefits of convalescent serum outweigh its 
possible risks in SARS-CoV-2 infected individuals with significant oxygen requirements. 
Known Risks of Plasma Transfusion 
Risks of any transfusion of plasma include: fever, chills, rash, headache, serious allergic 
reactions, TRALI, TACO, transmission of infectious agents.  
The chances of any of these occurring are as follows: 
Acute hemolytic reaction: 1 in 40,000 units transfused 
Febrile transfusion reaction: 1 in 100 to 1 in 1000 units transfused 
Urticarial reaction (hives): 1 in 100 units transfused 
Anaphylaxis: 1 in 20,000 to 1 in 50,000 units transfused 
Transfusion related acute lung injury (TRALI): 1 in 1,200 to 1 in 190,000 units 
transfused 
Transfusion related circulatory overload (TACO): less than 1 in 100 units transfused 
Transmission of Hepatitis B: less than 1 in 250,000 units transfused 
Transmission of Hepatitis C: less than 1 in 1,000,000 units transfused 
Transmission of HIV: less than 1 in 1,000,000 units transfused 
Hypothetical Risks of Plasma Transfusion 
There is a theoretical risk of antibody-mediated enhancement of infection (ADE). ADE 
has been shown to occur for several viral diseases, most notably flaviviruses including 
Dengue and Zika50, and involves an enhancement of disease in the presence of non-
neutralizing or poorly neutralizing antibodies. The concern has been raised that the 
highly variable presentation of COVID-19 may in part be due to an ADE phenomenon51-
52 due to partially cross-reacting antibodies from other human coronaviruses, most likely 
OC43 or HKU1 as they, like SARS-CoV-2 are members of the Beta-coronavirus family 
and are more likely to be cross reactive. Such ADE phenomena have been seen in both 
SARS53-54 and MERS55-56 in animal studies so are definitely of concern in COVID-19. 
While it would be expected that COVID-19 convalescent plasma would have high titers 
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of neutralizing antibody against SARS2-CoV-2, this is not always the case and antibody 
levels can vary57. When plasma from donors who only test positive by serology are 
added into the pool of available COVID convalescent plasma the concern rises further.  
Just as low neutralizing antibody levels can potentially cause issue due to ADE, high 
levels of anti-Spike IgG were found to be directly responsible for increased acute lung 
injury in a Chinese macaque model of SARS infection58. We must be concerned of the 
danger of both too low and too high a level of neutralizing antibodies in convalescent 
plasma. The use of COVID convalescent plasma must be carefully studied over a range 
of antibody levels to be sure it is safe to use at any level. This study is designed to 
detect any evidence of worsening respiratory status based on actual antibody level in 
the plasma transfused. 
Another theoretical risk is that administering antibody to those with an active SARS-
CoV-2 infection may treat the disease but modify the native immune response such that 
treated individuals mount an attenuated humoral immune response. This would leave 
them vulnerable to subsequent re-infection. Such a phenomenon has been seen in 
respiratory syncytial virus where passive antibody treatment before vaccination with 
respiratory syncytial virus was shown to attenuate humoral but not cellular immunity59. 
This has not been demonstrated in coronaviruses to this point. 
Risks of Laboratory Testing  
For all patients there will be multiple blood draws. For female patients of childbearing 
years, a serum pregnancy test will be sent before a unit of plasma is ordered, and if 
positive they will be removed from the study, whenever possible this test will be added 
on to previously drawn blood or done at the same time as another blood draw. A blood 
draw carries the common risks of bleeding, bruising, and pain, and the rare risks of 
blood clot, infection, light-headedness, dizziness, and fainting. 
For all patients there will multiple nasopharyngeal swabs. The risks of a nasopharyngeal 
swab: local discomfort, vomiting. 
Confidentiality 
Risks for this study include breach of confidentiality. To minimize this risk all case forms 
will use a code consisting of a unique number. A list will be kept that links the patient’s 
name and health system medical record number to the code. This list will be kept in a 
securely in the RedCap database which will be used to store patient date. Only study 
personnel will have access to the list and the case report forms. A list of the patients 
involved in the study will be kept within the EPIC EMR in order to facilitate access to the 
patient’s records for purposes of the study and to prevent recruitment of patients who 
are already in the study. The list will be private, maintained by the study principal 
investigator at each site with their lead coordinator, and accessible only to appropriate 
study personnel. 
4.2 Potential Benefits 
The potential benefits of treatment with COVID-19 convalescent plasma in patients with 
respiratory symptoms, requiring oxygens, and at high risk for requiring ICU admission 
are not known. However, it is anticipated that treatment will decrease the risk of disease 
progression requiring ICU admission and progression to mechanical ventilation. 
The potential benefits of treatment with COVID-19 convalescent plasma in patients 
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already requiring mechanical ventilation are even less clear. It is anticipated that 
treatment will reduce the overall mortality and increase the chance of the patient no 
longer requiring mechanical ventilation. 
4.3Adequacy of Protection Against Risks  
Risk-Benefit Ratio 
The dangers of plasma transfusion in general are well known and well described. The 
probability of their occurrence in predictable. The likelihood of the hypothetical risks of 
COVID-19 convalescent plasma transfusion are unknown but, in those studies currently 
available the overall use appears safe. 
Therefore, the risks to subjects are reasonable in relation to potential to directly benefit 
the participant by reducing the morbidity and mortality of COVID-19 as well as the 
importance of the knowledge that is expected to result.  
At all times, the risk-benefit ratio will be considered when recruiting a patient to the 
study. 
Recruitment and Informed Consent  
• A waiver of consent for screening will be sought for this trial in order to identify 
potential patients via the EMR. 
• Patients may be identified via an automated search of the Electronic Medical 
Record (EMR), which has already been built and is currently used to identify 
potential patients for clinical trials.  
• The search in the EMR will automatically narrow the search to patients in the 
appropriate age range (both female and male patients), who have tested positive 
for SARS-CoV-2. The search also identifies the amount of oxygen given to the 
patient and whether they are on a ventilator. 
• Patients may also be referred directly from the patient’s attending physician 
and/or the local site investigator 
• The inclusion and exclusion criteria for the study are listed in Section 2.3. Review 
and determination of eligibility will be conducted by the study coordinator with 
additional review of any subjects by the site principal investigator or other 
appropriate physician investigator for this study when the site principal 
investigator is not available.  
• After initial screening for inclusion and exclusion criteria, and with approval of the 
patient’s attending physician, the patient or his LAR will be approached to 
participate in the study by highly experienced study coordinators and/or a 
physician member of the study team. The background, purpose, basic 
requirements for participation, benefits, and risks of the study will be explained to 
the patient. The consent provider will explain that the cost of the study drug and 
any study procedures will be covered by the study with no expense to the patient. 
Patients will have adequate time to read the informed consent form and be given 
the opportunity to ask questions of the coordinator or investigator and have their 
questions answered to their satisfaction. 
• All discussions with the patient will be conducted remotely as per established 
emergency policies developed by the Beaumont IRB and Research 
Administration for consenting during this pandemic in order to maximize the 
safety of all involved and reduce the utilization of needed personal protective 
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equipment. All consenting will be witnessed by a third part from Beaumont and 
both the consent provider and the witness will document the consent in a 
research note in the patient’s clinical record in the EMR. 
• No pressure will be placed on patients to participate in the trial and they will be 
assured that their medical care will continue without any negative impact whether 
they participate in the study or not. 
• Written informed consent will be obtained from all study participants. 
• No parental consent will be necessary for this study as no patients under age 18 
will be enrolled. 
• Consent by an LAR may be utilized for this study as the participants may not be 
able to consent themselves and the treatment is considered potentially lifesaving 
at this time. 
• Oversight and study management will be provided by the PI and the Beaumont 
Urology Research Director. Monitoring will be provided by the Beaumont 
Research Coordinating Center. 
• All consent provider training and consent audits will be managed by the 
Beaumont Research Manager or her delegate. 
• No work will begin on this project until approval is granted by the Beaumont 
Health IRB. 
Protection against Risk  
All known risks will be specified in the informed consent form so participants are aware 
of the potential for adverse events and what those might be. 
Maintenance of Confidentiality:  
All appropriate measures will be taken to protect the identity of subjects and the 
confidentiality of collected data.  
Data will be collected using study-specific source documents which are included in this 
document. The data will be stored in the RedCap database, a secure hospital-based 
computer system with password protection. The author of an entry is easily identifiable, 
and the system is such that editing of documents and the person who edited it is 
tracked. The study personnel responsible for data collection will be trained to ensure 
reliability and quality of the data and the data will be monitored by the Beaumont 
Research Coordinating Center. All patient identifiers will be removed from the collected 
data to ensure HIPAA compliance and patient confidentiality. Patient data will be 
identified using initials and a patient study number. Any communication relating to the 
study, study documents, and electronic databases will identify patients by initials and 
their assigned number only.  
A patient identification log will be kept permitting easy identification of each patient 
during and after the study. The patient identification log will be confidential and will be 
kept in a secure location in the study office. To ensure confidentiality, no copy will be 
made. The log will link the patient’s name and medical record number to the unique 
study identification number. An electronic list of patients in the study, only available to 
study personnel, will be kept within the EPIC EMR of our health care system for use in 
rapidly accessing the patient’s health information for purposes of the study and to 
assure that no patient is recruited to the study more than once. When the study and all 
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review is complete, the list linking the study code to identifiers will be destroyed and the 
patient list within the EMR will be deleted. 
In accordance with ICH/GCP (International Conference on Harmonization/Good Clinical 
Practice) guidelines, the study team will maintain all source documents that support the 
data collected from each patient, as well as all study documents specified in ICH/GCP 
Section 8, Essential Documents for the Conduct of a Clinical Trial, and all study 
documents as specified by appropriate regulatory requirements. All documents related 
to the study will be kept in a secure location in the study office and will be preserved for 
a minimum of eleven years as required by internal policy either within the study office or 
another approved location for long-term secure storage. 
Adverse Events: 
An adverse event (AE) can be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of 
an investigational product, whether or not considered related to the investigational 
product. 
The occurrence of an AE may come to the attention of study personnel during at any 
point in the study. The period of observation for which AEs are to be collected will begin 
after the subject has signed the ICF and will continue throughout their participation in 
the study. All AEs, whether reported by the subject or noted by study personnel, will be 
recorded in the subject’s research chart. 
Information to be collected includes event description, time of onset, investigator’s 
assessment of severity, investigator’s assessment of relationship to study drug, and 
time of resolution/stabilization of the event. All AEs occurring while on study will be 
documented appropriately regardless of their relationship to the study treatment. AEs 
will be followed to adequate resolution. 
Any medical condition that is present at the time that the subject is screened will be 
considered as baseline and not reported as an AE. However, if the condition 
deteriorates at any time during the study, it will be recorded as an AE. Any laboratory 
abnormality not considered to be clinically significant by the investigator will not be 
considered an AE. All AEs will be graded for intensity and relationship to the study 
treatment. 
One of the investigators will determine the relationship between the study treatment and 
the occurrence of an AE as defined below: 
• Definitely related events are those that the investigator determines are 
definitely related to the intervention, and for which the investigator believes no 
alternative etiology exists. 
• Probably related events are those for which the investigator believes there is a 
reasonable likelihood the AE may have been caused by the intervention 
involved in the research. 
• Probably not related events are those for which the investigator believes there 
is a reasonable likelihood the AE may have been caused by other factors and 
not caused by the intervention involved in the research. 
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• Unrelated events are those that the investigator determines are not related to 
the intervention either due to timing or a confirmed alternative cause. 
• Unable to Determine: The investigator is unable to determine the likelihood that 
the AE and the study treatment have a causal relationship. 
Serious Adverse Events 
An adverse event or suspected adverse event is considered serious if, in the view of the 
investigator, the medical monitor, or the sponsor, it results in any of the following 
outcomes:  
• death, 
• a life-threatening adverse event,   
• inpatient hospitalization or prolongation of existing hospitalization, 
• a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or 
• a congenital anomaly/birth defect. 
An adverse event is considered “life-threatening” if, in the view of the investigator, the 
medical monitor, or the sponsor, its occurrence places the patient or subject at 
immediate risk of death. It does not include an adverse event that had it occurred in a 
more severe form, might have caused death. 
Important medical events that do not meet the criteria of resulting in death, being life-
threatening, or requiring hospitalization may still be considered serious when, based 
upon appropriate medical judgment, they might jeopardize the subject’s life and may 
require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. An example of this would be an early allergic reaction that does not reach the 
level of life-threatening due to early medical intervention with steroids and 
bronchodialators. 
Unanticipated Problems 
Unanticipated problems, in general, to include any incident, experience, or outcome that 
meets all of the following criteria: 
• Unexpected (in terms of nature, severity, or frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied; 
• Related or possibly related to participation in the research (in this guidance 
document, possibly related means there is a reasonable possibility that the 
incident, experience, or outcome may have been caused by the procedures 
involved in the research); and 
• Suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized. 
Data and Safety Monitoring Plan  
This study protocol will employ rigorous methods to ensure data safety. Human subject 
safeguards will include at a minimum, completion of Human Subjects Protection 
Training. In the event that any study participant has a significant adverse reaction 
related to the study, standard of care treatment to address the SAE for the participant 
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will be followed. The attending team for each participant will be directly involved and 
know to inform the site principal investigator, or the research coordinator should there 
be a significant worsening of the patient’s clinical status. 
Adverse Event Reporting   
If an untoward event occurs, it will be reported by the principal investigator in 
accordance with the Department of Health and Human Services (DHHS) code of federal 
regulations (Title 45, Part 46).  
There are two categories of AEs: 1) Serious Adverse Events and 2) Adverse Events. 
Serious adverse events are required to be reported within 48 hours of knowledge of the 
event. Adverse events not in the “serious” category but judged to be “severe” or “life-
threatening” are also subject to the 48 hours reporting requirement. Copies of reports of 
all SAEs will be forwarded to the IRB and the DSMB. The PI will be responsible for 
generating a summary report for the IRB and DSMB. The report will document that a 
review of data and outcomes took place on a given date, when the event occurred, and 
when the PI became aware of it. Adverse events are reported to the IRB during the 
regular progress reports and will be reported to the DSMB at the same time. 
Unanticipated problems that are serious adverse events will be reported to the IRB and 
the DSMB within 48 hours of the investigator becoming aware of the event. 
Any other unanticipated problem which is not also an SAE will be reported to the IRB 
within 1 week of the investigator becoming aware of the problem. 
Compliance with Policy/Regulation 
Protection of Human Patients  
Compliance with Informed Consent Regulations (U.S. 21 CFR Part 50) will be strictly 
maintained. Informed consent audits will be conducted by the Infectious Diseases 
Clinical Research Manager and kept on file, per Research Institute policy. 
Compliance with Electronic Records; Electronic Signatures Regulations 
This study will be conducted in compliance with the regulations on electronic records 
and electronic signatures and will comply with the Guidance on Computerized Systems 
used in Clinical Trials.  
Patient Confidentiality 
A report of the results of this study may be published but patients’ names will not be 
disclosed in these documents. Appropriate precautions will be taken to maintain 
confidentiality of medical records and personal information.  
 
Data Safety Monitoring Board 
A formal data safety monitoring board will be established for this study per NIH 
guidelines. The membership will consist of independent experts without conflicts of 
interest and without direct involvement in this study. The membership shall consist of 4 
physicians including an Infectious Diseases specialist and a Hematologist. The fifth 
member of the DSMB will be a biostatistician. The DSMB will meet within 1 week of the 
first patient being enrolled at least monthly to review the data thereafter. The exact 
schedule may be modified depending on the level of enrollment with faster enrollment 
leading to more frequent meetings and slower enrollment leading to less frequent 
meetings though the meetings will never be less then quarterly. At any time the halting 
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criteria for the study are met the DSMB will meet to review what occurred and make a 
decision on whether the study can resume. 
Halting Criteria for the Study 
The study enrollment and dosing will be stopped and an ad hoc review by the DSMB 
will be performed if any of the specific following events occur or, if in the judgment of the 
study physician, subject safety is at risk of being compromised: 
1. Death within one hour of plasma infusion 
2. Occurrence of more than a single life-threatening allergic/hypersensitivity 
reaction (anaphylaxis), manifested by bronchospasm with or without urticaria or 
angioedema requiring hemodynamic support with pressor medications or 
mechanical ventilation. 
3. An overall pattern of symptomatic, clinical, or laboratory events that the 
investigator feels is associated with the study product and that may appear minor 
in terms of individual events but that collectively may represent a serious 
potential concern for safety. 
4. Any unanticipated problem which is felt to alter the overall risk-benefit ratio of the 
study. 
Upon completion of this ad hoc review the DSMB will determine if study entry or study 
dosing should be interrupted or if study entry and study dosing may continue according 
to the protocol. 
Halting Criteria/Rules for Subject Infusion 
The rules for halting plasma transfusion are established by policy at Beaumont Health 
and will be followed by nursing staff who are supervising the transfusion. Decision to 
discontinue or resume the transfusion with or without medication treatment will be made 
by the study investigator based on the pre-established policies. See Beaumont Health 
Policy 7876626. 
At the discretion of the study investigator or the clinical care team pretreatment to 
minimize transfusion reactions (e.g. acetaminophen, diphenhydramine) may be given to 
a participant 
If an adverse reaction develops during infusion, the infusion may be slowed or stopped 
at the investigator’s discretion. 
Most reactions to plasma are relatively minor and the infusion can generally be 
continued. Infusion site burning and non-allergic systemic effects can generally be 
managed with slowing of the infusion. Infusion can generally be continued in cases of 
itching or hives after pausing the transfusion, administering antihistamines, and 
observing the patient for worsening. 
Severe reactions such as, anaphylaxis, bronchospasm, respiratory compromise and 
hypotension, will require discontinuation of the infusion. 
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REFERENCES: 
1. 
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 
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Bialek S, Boundy E, Bowen V, et al (CDC COVID-19 Response Team). Severe 
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McCarthy A. U.S. COVID-19 Fatality Rate Steady: About 1 Percent. National 
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11. https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-
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12. Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a 
treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J 
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13. Molina JM, Delaugerre C, Le Goff Jet al. No evidence of rapid antiviral clearance 
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14. Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine 
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Page | 26 
 
15. Mahévas M, Tran V-T, Roumier M, et al. No evidence of clinical efficacy of 
hydroxychloroquine in patients hospitalized for COVID-19 infection and requiring 
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16. Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with COVID-19: an 
open-label, 
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17. Chu CM, Cheng VCC, Hung IFN, et al on behalf of the HKU/UCH SARS Study 
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18. Cao B, Wang Y, Wen D, et al A Trial of Lopinavir-Ritonavir in Adults Hospitalized 
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&sfpd_s=&sfpd_e=&rfpd_s=&rfpd_e=&lupd_s=&lupd_e=&sort=  
20. Marano G, Vaglio S, Pupella S, Facco G, Catalano L, Liumbruno GM, Grazzini G. 
Convalescent plasma: new evidence for an old therapeutic tool? Blood Transfus. 
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21. Luke TC, Casadevall A, Watowich SJ, et al. Hark back: passive immunotherapy 
for influenza and other serious infections. Crit Care Med. 2010 Apr;38(4 
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22. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The effectiveness of 
convalescent plasma and hyperimmune immunoglobulin for the treatment of 
severe acute respiratory infections of viral etiology: a systematic review and 
exploratory meta-analysis. J Infect Dis. 2015;211:80-90. 
23. Tiberghien P, de Lamballerie X, Morel P, et al. Collecting and evaluating 
convalescent plasma for COVID-19 treatment: why and how? Vox Sang. 2020 Apr 
2. doi: 10.1111/vox.12926. [Epub ahead of print] 
24. Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis: convalescent blood 
products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern 
Med. 2006;145:599-609. 
25. Sahr F, Ansumana R, Massaquoi T, Idriss B, Sesay F, Lamin J, et al. Evaluation 
of convalescent whole blood for treating Ebola Virus Disease in Freetown, Sierra 
Leone. Journal of Infection. 2017;74(3):302–309. 
26. van Griensven J, Edwards T, de Lamballerie X, et al. Evaluation of Convalescent 
Plasma for Ebola Virus Disease in Guinea. NEJM. 2016;374(1):33-42 
27. Zhou XZ, Zhao M, Wang FS, et al. Epidemiologic features, clinical diagnosis, and 
therapy of first cluster of patients with severe acute respiratory syndrome in 
Beijing area. Zhonghua Yi Xue Za Zhi. 2003;83: 1018-22 (Chinese Language) 
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Page | 27 
 
28. Wong VWS, Dai D, Wu AKL, Sung JJY. Treatment of severe acute respiratory 
syndrome with convalescent plasma. Hong Kong Med J. 2003;9(3): 199-201 
29. Kong L, Letter to the Editor. Transfus and Apher Sci. 2003;29: 101 
30. Yeh K-M, Chiueh T-S, Siu L, et al. Experience of using convalescent plasma for 
severe acute respiratory syndrome among healthcare workers in a Taiwan 
hospital. Journal of Antimicrobial Chemotherapy. 2005;56(5): 919–922. 
31. Soo YOY, Cheng Y, Wong R, et al. Retrospective comparison of convalescent 
plasma with continuing high-dose methylprednisolone treatment in SARS patients. 
Clin Microbiol and Infect. 2004;10(7): 676-78 
32. Cheng Y, Wong R, Soo Y, et al. Use of convalescent plasma therapy in SARS 
patients in Hong Kong. European Journal of Clinical Microbiology and Infectious 
Diseases. 2005;24(1): 44–46. 
33. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The effectiveness of 
convalescent plasma and hyperimmune immunoglobulin for the treatment of 
severe acute respiratory infections of viral etiology: a systematic review and 
exploratory meta-analysis. The Journal of infectious diseases. 2015;211(1):80–90. 
34. Ko JH, Seok H, Cho SY, et al. Challenges of convalescent plasma infusion 
therapy in Middle East respiratory coronavirus infection: a single center 
experience. Antiviral therapy. 2018;23(7): 617–622. 
35. Chun S, Chung CR, Ha YE, et al. Possible transfusion-related acute lung injury 
following convalescent plasma transfusion in a patient with Middle East respiratory 
syndrome. Ann Lab Med. 2016;36: 393-95. 
36. Arabi YM, Hajeer AH, Luke T, et al. Feasibility of using convalescent plasma 
immunotherapy for MERS-CoV infection, Saudi Arabia. Emerging infectious 
diseases. 2016;22(9): 1554-61. 
37. Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically ill patients with COVID-19 
with convalescent plasma. JAMA. 2020;323(16): 15-82-1589. 
38. Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe 
COVID-19 patients. PNAS. 2020;117(17): 9490-96. 
39. Ye M, Fu D, Ren Y, et al. Treatment with convalescent plasma for COVID-19 
patients in Wuhan, China. J Med Virol. 2020; doi: 10.1002/jmv.25882. [Epub 
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40. Zhang B, Liu S, Tan T. et al. Treatment With Convalescent Plasma for Critically Ill 
Patients With SARS-CoV-2 Infection. Chest. 2020; [E-Pub ahead of print]. 
doi.org/10.1016/j.chest.2020.03.039 
41. Ahn JY, Sohn Y, Lee SH et al. Use of Convalescent Plasma Therapy in Two 
COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea. J Korean 
Med Sci. 2020;35(14): e149 
 
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42. Zeng QL, Yu ZJ, Gou JJ, et al. Effect of Convalescent Plasma Therapy on Viral 
Shedding and Survival in COVID-19 Patients. J Infect Dis. 2020 Apr 29. pii: 
jiaa228. doi: 10.1093/infdis/jiaa228. [Epub ahead of print] 
43. Rajendran K, Narayanasamy K, Rangarajan J, et al. Convalescent plasma 
transfusion for the treatment of COVID-19: Systematic review. J Med Virol. 2020. 
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44. Casadevall A, Pirofski L. The convalescent sera option for containing COVID-19. J 
Clin Invest. 2020; 120(4): 1545-1648. 
45. Casadevall A, Pirofski L. Antibody-mediated regulation of cellular immunity and 
the inflammatory response. TRENDS in Immunology. 2003;24(9):474–478. 
46. Rojas M ,Rodriguez Y, Monsalve DM, et al. Convalescent plasma in Covid-19: 
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47. Wan J, Sun W, Li X, et al. Inflammation inhibitors were remarkably up-regulated in 
plasma of severe acute respiratory syndrome patients at progressive phase. 
Proteomics. 2006;6(9): 2886-94 
48. Wölfel R, Corman VM, Guggemos W, et al. (2020). Virological assessment of 
hospitalized patients with COVID-2019. Nature. doi:10.1038/s41586-020-2196-x 
49. Zhang G, Nie S, Zhang Z, Zhang Z. Longitudinal Change of SARS-Cov2 
Antibodies in Patients with COVID-19. J Infect Dis. 2020 May 2. pii: jiaa229. doi: 
10.1093/infdis/jiaa229. [Epub ahead of print] 
50. Khandia R, Munjal A, Dhama K, et al. Modulation of Dengue/Zika Virus 
Pathogenicity by Antibody-Dependent Enhancement and Strategies to Protect 
Against Enhancement in Zika Virus Infection. Front Immunol. 2018;9: 597. 
51. Tetro JA. Is COVID-19 receiving ADE from other coronaviruses? Microbes and 
Infection. 2020;22: 72-73 
52. Iwasaki A and Yang Y. The potential danger of suboptimal antibody responses in 
COVID-19. Nat Rev Immunol. 2020. doi: 10.1038/s41577-020-0321-6. [Epub 
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53. Yip MS, Cheung CY, Li PH et al. Investigation of Antibody-Dependent 
Enhancement (ADE) of SARS coronavirus infection and its role in pathogenesis of 
SARS.BMC Proceedings. 2011; 5(Suppl 1): P80. 
54. Houser KV, Broadbent AJ, Gretebeck L, et al. Enhanced inflammation in New 
Zealand white rabbits when MERS-CoV reinfection occurs in the absence of 
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55. Houser KV, Broadbent AJ, Gretebeck L, et al. Enhanced inflammation in New 
Zealand white rabbits when MERS-CoV reinfection occurs in the absence of 
neutralizing antibody. PLoS Pathog. 2017 Aug 17;13(8):e1006565. 
 
 
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56. Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, et al. Molecular mechanism for 
antibody-dependent enhancement of coronavirus entry. Journal of Virology. 
2020;94(5). 
57. Zhang L, Pang R, Xue X, et al. Anti-SARS-CoV-2 virus antibody levels in 
convalescent plasma of six donors who have recovered from COVID-19. Aging. 
2020;12(8): 6536-6542. 
58. Liu L, Wei Q, Lin Q, et al. Anti-spike IgG causes severe acute lung injury by 
skewing macrophage responses during acute SARS-CoV infection. JCI Insight. 
2019;4(4). pii: 123158 
59. Crowe JE, Firestone C-Y, Murphy BR. Passively acquired antibodies suppress 
humoral but not cell-mediated immunity in mice immunized with live attenuated 
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2001;167(7):3910–3918. 
 
 
 
 
 
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ABACCuS Initial Data Collection Form 
 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
 
Date of admission: ______________ 
 
 
Date of initial symptoms: ______________  
 
Date of first +COVID PCR: ______________ 
 
Hospitalization Status: Standard floor/COVID Unit/MPCU/ICU 
 
Symptoms onset date: 
_____________ Cough  
 
_______________ SOB 
_____________ Fever 
 
_______________ Lack of taste 
_____________ Nausea 
 
_______________ Lack of smell 
_____________ Vomiting                  _______________ Muscle aches  
_____________ Diarrhea 
 
_______________ Headache  
 
 
Vital signs in last 24 hours (Current reflects measurement immediately prior to transfusion) 
Maximum temperature: _____ 
Minimum temperature: _____ 
Current temperature: _____ 
Maximum heart rate:  _____  
Minimum heart rate: _____ 
 
Current heart rate: _____ 
Maximum blood pressure (based on mean arterial pressure): _____ 
MAP: _____ 
Minimum blood pressure (based on mean arterial pressure): _____ 
MAP: _____ 
Current blood pressure: _____ 
 
 
 
 
 
MAP: _____ 
Maximum O2 patient was on and the method of delivery: ______________________________ 
Minimum O2 patient is on and the method of delivery: ______________________________ 
Minimum O2 saturation, O2 delivered, and the method of delivery: ______________________________ 
Maximum O2 saturation, O2 delivered and the method of delivery: ______________________________ 
Current O2 saturation, O2 delivered, and the method of delivery: ______________________________ 
Maximum respiratory rate: _____ 
Minimum respiratory rate: _____ 
Current respiratory rate: _____ 
 
SOFA Score: ________ 
APACHE II Score: ________  
H-Score: ________ 
 
Include with source documentation the report from EPIC EMR of the most recent of the following lab 
results prior to transfusion of IP if available: 
 
CBC with differential (if a more recent CBC without differential is available include as well) 
CMP (if more recent components of the CMP are available include as well) 
Triglycerides, Ferritin, Fibrinogen, CRP, ESR, LDH, D Dimer, IL-6, CK, COVID PCR 
Pregnancy test (for women of childbearing potential), Type and Screen 
 
Include with source documentation the following reports during the admission for COVID if available: 
Initial chest CT, most recent chest CT, initial chest X-ray, most recent chest X-ray, initial echocardiogram, most 
recent echocardiogram 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
 
 
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ABACCuS Demographics/Medical History Data Collection Form: 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
 
Demographics 
Age: _____  
 
Sex: _____  
 
Race: ____________________ 
Date of birth: __________  
 
 
 
Profession: ____________________ 
Zip Code of Residence: __________ 
 
Medical History 
• Diabetes mellitus: Y / N 
• Cardiovascular disease: Y / N 
• Chronic lung disease: Y / N 
• Chronic kidney disease: Y / N 
• Hypertension: Y / N 
• Immunocompromised: Y / N 
o Transplant [SOT] : Y / N 
o Hematologic malignancy: Y / N 
o Active chemotherapy: Y / N 
o Chronic steroids >0.5 mg/kg/day prednisone equivalent: Y / N 
o Congenital or acquired immunodeficiency: Y / N 
o Splenectomy: Y / N 
o Biologic agents for immunosuppression: Y / N 
o Other: Y / N __________________________ 
Other Major Medical Conditions: 
_____________________________________________________________________________ 
_____________________________________________________________________________ 
_____________________________________________________________________________ 
Current Medications: 
 
Append current medication list from EPIC EMR,  
 
Append ACE inhibitors and ARBs received during current admission, 
 
Append all steroids received during current admission,  
 
Append all antibiotics received during current admission,  
 
Append all anti-coagulation received during current admission,  
 
Append all vasopressors received during current admission, 
 
Append all treatments given specifically for COVID during current admission 
Chronic Medications: Append outpatient medication list from EPIC EMR 
 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
 
 
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ABACCuS Daily Vital Signs, Clinical and Laboratory Values Data Collection Form: 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
 
Study day #:_____ 
 
 
 
 
 
Date of record: ___________ 
Hospital day #: _____  
 
 
 
 
Date data recorded: ___________ 
 
For the calendar day indicated above: 
Maximum temperature: _____ 
Minimum temperature: _____ 
 
Maximum heart rate:  _____  
Minimum heart rate: _____ 
 
 
Maximum blood pressure (based on mean arterial pressure): _____ 
MAP: _____ 
Minimum blood pressure (based on mean arterial pressure): _____ 
MAP: _____ 
Maximum O2 patient was on and the method of delivery: ______________________________ 
Minimum O2 patient is on and the method of delivery: ______________________________ 
Minimum O2 saturation, O2 delivered, and the method of delivery: ______________________________ 
Maximum O2 saturation, O2 delivered and the method of delivery: ______________________________ 
Maximum respiratory rate: _____ 
Minimum respiratory rate: _____ 
 
Was the patient: On Ventilator: Y/N     
Proned: Y/N   
On Nitrox: Y/N  
On ECMO: Y/N  
Laboratory Values 
Markers of 
Inflammation 
and Other 
Value 
 
Complete Blood 
Count With 
Differential 
Value 
 
Metabolic 
Markers 
Value 
Ferritin 
 
 
WBC 
 
 
Sodium 
 
Fibrinogen 
 
 
Hemoglobin 
 
 
Potassium 
 
CRP 
 
 
Hematocrit 
 
 
Chloride 
 
ESR 
 
 
Platelets 
 
 
CO2 
 
CK 
 
 
Neutrophils 
 
 
BUN 
 
D-Dimer 
 
 
Lymphocytes 
 
 
Creatinine 
 
LDH 
 
 
Monocytes 
 
 
Glucose 
 
Interleukin-6 
 
 
Eosinophils 
 
 
Total Protein 
 
 
 
 
 
 
 
Albumin 
 
 
 
 
 
 
 
Globulin 
 
Triglycerides 
 
 
 
 
 
Alk Phos 
 
Procalcitonin 
 
 
 
 
 
ALT 
 
 
 
 
 
 
 
AST 
 
 
 
 
 
 
 
Total Bilirubin 
 
Append any chest imaging, EKG, or echocardiogram for this date of hospitalization 
Append any positive microbiology results for this date of hospitalization 
Append any blood gasses for this date of hospitalization 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
 
 
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ABACCuS Daily Medications Data Collection Form: 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
 
Study day #:_____ 
 
 
 
 
 
Date of record: ___________ 
Hospital day #: _____  
 
 
 
 
Date data recorded: ___________ 
 
For the calendar day indicated above: 
Was the Patient Sedated: Y/N 
 
 
Sedation Used: ______________________________ 
Was the Patient Paralyzed: Y/N 
 
 
Paralytic Used: ______________________________ 
Was the Patient on Pressors: Y/N 
 
 
Pressors Used: ______________________________ 
Medications Initiated on This Calendar Day: 
Medication 
Dose 
Route of 
Administration 
Frequency 
Time Started 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medications Discontinued or Completed on This Calendar Day: 
Medication 
Medication 
Medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Medications with Dose Modifications on This Calendar Day: 
Medication 
Dose Change 
Frequency Change 
Time of Change 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Append the medication administration record and any blood products for the above calendar date 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
 
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ABACCuS Serology Data Collection Form: 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
Plasma Unit Used: ______________________ 
 
Date and Time of Transfusion: _______________ 
Patient Baseline Serology:  
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology 1 Hour Post-Transfusion (+/- 5 min) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology 24 Hours Post-Transfusion (+/- 1 hour) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology 72 Hours Post-Transfusion (+/- 3 hours) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology 1 Week Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology 2 Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology 3 Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology 4 Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology Day of Discharge 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
 
 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
 
 
IRB NUMBER: 2020-198
IRB APPROVAL DATE: 08/26/2020

 
 
ABACCuS Protocol 
 
PI: Matthew Sims, MD PhD 
 
Page | 35 
 
ABACCuS Supplemental Serology Data Collection Form: 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
Plasma Unit Used: ______________________ 
 
Date and Time of Transfusion: _______________ 
 
Patient Serology _____ Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology _____ Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology _____ Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology _____ Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology _____ Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology _____ Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology _____ Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology _____ Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
Patient Serology _____ Weeks Post-Transfusion (+/- 1 day) 
IgA OD: __________  
IgG OD: __________  
Date and Time of Specimen: ________________ 
 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
 
IRB NUMBER: 2020-198
IRB APPROVAL DATE: 08/26/2020

 
 
ABACCuS Protocol 
 
PI: Matthew Sims, MD PhD 
 
Page | 36 
 
ABACCuS SARS-CoV-2 RT PCR Data Collection Form: 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
Plasma Unit Used: ______________________ 
 
Date and Time of Transfusion: _______________ 
Patient Qualifying RT PCR:  
Result: __________  
CT Value: __________ 
Date and Time of Specimen: ________________ 
Patient Pre-Transfusion RT PCR:  
Result: __________  
CT Value: __________ 
Date and Time of Specimen: ________________ 
Patient 24 hour Post-Transfusion RT PCR:  
Result: __________  
CT Value: __________ 
Date and Time of Specimen: ________________ 
Patient 72 hour Post-Transfusion RT PCR:  
Result: __________  
CT Value: __________ 
Date and Time of Specimen: ________________ 
Patient 7 Days Post-Transfusion RT PCR:  
Result: __________  
CT Value: __________ 
Date and Time of Specimen: ________________ 
Patient 14 Days Post-Transfusion RT PCR:  
Result: __________  
CT Value: __________ 
Date and Time of Specimen: ________________ 
 
 
 
 
 
 
 
 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
 
 
IRB NUMBER: 2020-198
IRB APPROVAL DATE: 08/26/2020

 
 
ABACCuS Protocol 
 
PI: Matthew Sims, MD PhD 
 
Page | 37 
 
ABACCuS 28 Safety Form: 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
Plasma Unit Used: ______________________ 
 
Date and Time of Transfusion: _______________ 
In the 2 hours after the transfusion: 
Did the patient have a rapid decline in respiratory status: Y/N 
 
 
 
If yes: Date and Time: _______________ 
 
Severity: _________________________ 
 
If yes: Description of the event: ________________________________________________________ 
Did the patient have a rapid decline in clinical status: Y/N  
 
 
 
If yes: Date and Time: _______________ 
 
Severity: _________________________ 
 
If yes: Description of the event: ________________________________________________________ 
In the 4 hours after the transfusion: 
Did the patient have a fever of >38°C: Y/N  
Tmax: _____ 
 
If yes: Date and Time: __________ 
Did the patient have an allergic reaction: Y/N 
 
 
 
If yes: Date and Time: __________ 
 
Conjunctival Edema: Y/N 
Edema of Oral Area: Y/N 
Periorbital Erythema/Edema: Y/N 
 
Generalized Flushing: Y/N 
Hypotension: Y/N 
 
Localized Angioedema: Y/N 
 
Maculopapular Rash: Y/N 
Pruritus (itching): Y/N  
Bronchospasm: Y/N 
 
Urticaria (hives): Y/N  
 
 
 
Severity: _________________________ 
In the 6 hours after the transfusion: 
Was the patient diagnosed with Transfusion Associated Circulatory Overload (TACO): Y/N 
 
If yes: Date and Time: _______________ 
 
Severity: _________________________ 
Was the patient diagnosed with Transfusion Related Acute Lung Injury (TRALI): Y/N 
 
If yes: Date and Time: _______________ 
 
Severity: _________________________ 
In the 24 hours after the transfusion: 
Did the patient have evidence of cytokine storm: Y/N  
 
 
 
 
If yes: Date and Time: _______________ 
 
Severity: _________________________ 
 
If yes: Description of the event: ___________________________________________________ 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
 
 
IRB NUMBER: 2020-198
IRB APPROVAL DATE: 08/26/2020

 
 
ABACCuS Protocol 
 
PI: Matthew Sims, MD PhD 
 
Page | 38 
 
ABACCuS 28 Day Outcome Form Group A: 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
Plasma Unit Used: ______________________ 
 
Date and Time of Transfusion: _______________ 
Primary Outcome: 
Was the patient intubated within 28 days of the transfusion:  Y/N 
 
If intubated: 
Date of intubation: __________ 
Study Day #: _____ 
Secondary Outcomes: 
Outcome on a 7-point ordinal scale: 
 Not hospitalized,   (1) No limitations on activities 
 
 (2) Limitation on activities  
 Hospitalized,  
 (3) Not requiring supplemental O2  
 (4) Requiring supplemental O2 
 
 
 
 (5) On non-invasive ventilation or high flow O2 devices 
 
 
 
 (6) On invasive mechanical ventilation or ECMO  
 Death 
 
 (7) Deceased 
Cardio-circulatory arrest within 28 days of transfusion: Y/N 
 
 
If so date: __________ 
Renal failure by RIFLE criteria within 28 days of transfusion: Y/N 
 
If so date: __________ 
Liver failure within 28 days of transfusion: Y/N  
 
 
 
If so date: __________ 
 
New rise in ALT or AST >5x the upper limit of normal Y/N 
 
Significant worsening of preexisting liver failure rise in ALT or AST of >25%: Y/N 
Evidence of cytokine storm based on inflammatory markers: Y/N 
 
If so date: __________ 
Days on ventilator: _____ Days off ventilator: _____ Days on coldflow: _____ 
 
Days on CPAP: _____ 
Days on BIPAP: _____ 
Days on non-rebreather: _____ 
Days on NC: _____  
Days on Hiflo NC: _____ Discharge on new home O2: Y/N 
Requirement of pressor support: Y/N 
 
Pressors used and dates of use: _______________  _______________  _______________ 
 
 
          _______________  _______________  _______________  _______________ 
In hospital mortality: Y/N 
Within 28 days: Y/N  
In ICU: Y/N  
If so date: __________ 
Length of Stay: _____ 
ICU Length of Stay: _____  
 
Readmission: Y/N  
If so diagnosis: ____________________ 
If so date: __________ 
 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
IRB NUMBER: 2020-198
IRB APPROVAL DATE: 08/26/2020

 
 
ABACCuS Protocol 
 
PI: Matthew Sims, MD PhD 
 
Page | 39 
 
ABACCuS Final Outcome Form Group A: 
Patient Initials/Study ID: ______________  
 
Date of Enrollment: ______________ 
Plasma Unit Used: ______________________ 
 
Date and Time of Transfusion: _______________ 
Primary Outcome: 
Was the patient intubated after the transfusion:  Y/N 
 
If intubated: 
Date of intubation: __________ 
Study Day #: _____ 
Secondary Outcomes: 
Final outcome on a 7-point ordinal scale: 
 Not hospitalized,   (1) No limitations on activities 
 
 (2) Limitation on activities  
 Hospitalized,  
 (3) Not requiring supplemental O2  
 (4) Requiring supplemental O2 
 
 
 
 (5) On non-invasive ventilation or high flow O2 devices 
 
 
 
 (6) On invasive mechanical ventilation or ECMO  
 Death 
 
 (7) Deceased 
Cardio-circulatory arrest after transfusion: Y/N  
 
 
 
If so date: __________ 
Renal failure by RIFLE criteria after transfusion: Y/N  
 
 
If so date: __________ 
Liver failure after transfusion: Y/N  
 
 
 
 
 
If so date: __________ 
 
New rise in ALT or AST >5x the upper limit of normal Y/N 
 
Significant worsening of preexisting liver failure rise in ALT or AST of >25%: Y/N 
Evidence of cytokine storm based on inflammatory markers: Y/N 
 
If so date: __________ 
Days on ventilator: _____ Days off ventilator: _____ Days on coldflow: _____ 
 
Days on CPAP: _____ 
Days on BIPAP: _____ 
Days on non-rebreather: _____ 
Days on NC: _____  
Days on Hiflo NC: _____ Discharge on new home O2: Y/N 
Requirement of pressor support: Y/N 
 
Pressors used and dates of use: _______________  _______________  _______________ 
 
 
          _______________  _______________  _______________  _______________ 
In hospital mortality: Y/N 
In ICU: Y/N  
 
 
 
 
If so date: __________ 
Length of Stay: _____ 
ICU Length of Stay: _____  
 
Readmission: Y/N  
If so diagnosis: ____________________ 
If so date: __________ 
 
______________________________________________________________________ 
Signature of coordinator 
 
 
 
 
 
Date 
 
______________________________________________________________________ 
Signature of Investigator reviewing data 
 
 
 
Date 
 
IRB NUMBER: 2020-198
IRB APPROVAL DATE: 08/26/2020