key: cord-261653-0vtghtp7
authors: Andersen, Kylie J.; Klassen, Stephen A.; Larson, Kathryn F.; Ripoll, Juan G.; Senefeld, Jonathon W.; Clayburn, Andrew J.; Shepherd, John R.A.; Tseng, Andrew S.; Wiggins, Chad C.; Johnson, Christopher P.; Miller, Andrew D.; Baker, Sarah E.; Wright, R. Scott; Winters, Jeffrey L.; Stubbs, James R.; Joyner, Michael J.; van Buskirk, Camille M.
title: Recruitment Strategy for Potential COVID-19 Convalescent Plasma Donors
date: 2020-09-21
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2020.09.021
sha: 
doc_id: 261653
cord_uid: 0vtghtp7

nan

Coronavirus disease 2019 (COVID-19) represents a pandemic and global health crisis. In the first wave of the disease in the US, COVID-19 was diagnosed in approximately two million individuals and contributed to over one-hundred thousand deaths. 1 The number of COVID-19 diagnoses and related deaths are anticipated to perpetuate in subsequent waves of the disease. 2 The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which causes COVID-19 appears to be a new human pathogen with limited efficacious treatments including the antiviral, remdesivir and the glucocorticoid, dexamethasone. 3, 4 However, there is robust historical precedent to anticipate that human convalescent plasma is a viable option for mitigation and treatment of COVID-19. 5, 6 Human convalescent plasma leverages the antibody response of a recently-sick and recovered COVID-19 patient as a plasma donor. 7 The donated plasma which is rich in neutralizing antibodies to the SARS-CoV-2 virus is transfused to a currently-sick COVID-19 patient to mitigate on-going symptomology and induce passive immunity. 7 Thus, the US Food and Drug Administration (US FDA) in collaboration with the Mayo Clinic and national blood banking community developed a national Expanded Access Program (EAP) to collect and distribute convalescent plasma donated by COVID-19 survivors. 8 Theoretically, within four to six weeks of the onset of the US COVID-19 outbreak, human convalescent plasma should have been readily available due to the existing plasma collection infrastructure within the blood banking community 9 and the large numbers of COVID-19 survivors who could have donated high-titer immunoglobulin-containing plasma. 10 However, logistical issues produced a convalescent plasma fulfillment gap that created an urgent need to develop strategies to recruit eligible donors at national, regional, and local blood centers. Thus, the present narrative overviews the strategy developed by our team to identify and recruit COVID-19 survivors to donate convalescent plasma at the Mayo Clinic Blood Donor Center in Rochester, Minnesota.

Emerging data from the COVID-19 pandemic support the use of convalescent plasma therapy.

There is evidence to suggest that SARS-CoV-2 elicits a robust immune response with high levels of antibodies and immunoglobulins (M and G) between 11-21 days after the onset of COVID-19, suggesting a relatively large window of time and high probability of successful extraction of high-titer anti-SARS-CoV-2 plasma from donors. 10 Consistent with this observation, convalescent plasma treated COVID-19 patients had large reductions in serum SARS-CoV-2 J o u r n a l P r e -p r o o f serum viral loads after convalescent plasma infusion, suggesting a viral neutralizing effect of the anti-SARS-CoV-2 antibodies. 11 Some theoretical concerns for the use of convalescent plasma therapy for COVID-19 have been raised, including the risk of transfusion-related lung injury (TRALI), transfusion-related circulatory overload (TACO), and antibody-dependent enhancement of COVID-19. 12 However, in a large study of 20,000 patients transfused with convalescent plasma there was no signal of toxicity beyond what is expected from plasma use in severely-ill patients. 8, 13 While the efficacy of convalescent plasma remains unknown, preliminary investigations have provided a signal of possible benefit in severely-ill COVID-19 patients. 14, 15 Thus, recruitment of COVID-19 survivors was fundamental to meet the rapidlygrowing demand for convalescent plasma as the pandemic progressed and clinical interest in convalescent plasma therapy increased.

Rochester, Minnesota required a strategy to interface with the community of recovering COVID-19 patients and recruit eligible convalescent plasma donors. To accommodate the growing magnitude and geographical spread of COVID-19 survivors and the changing convalescent donor eligibility criteria outlined by regulatory agencies and local institutions, we required this strategy to be inherently modifiable. Overall, this recruitment strategy utilized a simple survey, an algorithm for triaging donors, a workflow for connecting donors with Mayo Clinic Blood Donor Center, a team of physician navigators (including medical students) to screen eligible donors, and a support center for donor questions. This strategy may be adopted by other institutions to rapidly increase convalescent plasma donor recruitment.

To identify previously-ill recovered COVID-19 survivors that satisfied present and changing eligibility criteria to donate convalescent plasma, we employed a brief online survey hosted by the Research Electronic Data Capture (REDCap) system. 16, 17 To reduce user time-burden this survey was limited only to questions deemed necessary to determine donor eligibility and to maximize the retention of interested volunteers ( Table 1) 

Respondents were deemed ineligible to donate convalescent plasma and were immediately excluded from follow up by our team if they i) reported no positive COVID-19 laboratory test, ii) submitted an incomplete survey, iii) did not authorize follow up contact by our team, iv) or could not be contacted by our team for follow-up (Figure 1) . Volunteers were also excluded from follow up by our team if they declined contact authorization at any time. Ineligible respondents received an automated email to communicate both our gratitude and the reason for their J o u r n a l P r e -p r o o f ineligibility. This automated email also included a new call to action for interested volunteerswe encouraged the individuals (if eligible) to perform a standard blood donation to prevent future blood shortages and direct them to the AABB website (http://covidplasma.org/) which provides blood donation information. Also, our donor service center encouraged interested potential donors who reported COVID-19 symptoms but did not receive a COVID-19 clinical test to contact their healthcare provider for a serology test and then fill out the recruitment survey again if they were sero-positive.

Our web-based recruitment survey and all e-mail communications to interested potential donors contained the e-mail address for our convalescent plasma service center. The service center team used available resources from the US FDA, Mayo Clinic, and the blood banking community to support questions regarding donor eligibility and COVID-19 testing. 9,18 Also, the service center supported the physician navigator team by providing ongoing communication with screened eligible donors.

This convalescent plasma donor recruitment strategy had several key strengths:

1) The recruitment strategy had inherent scalability to meet the growing magnitude of recovering COVID-19 patients and enabled filtering by donor location to link the volunteer to a convenient donation center.

2) This strategy reduced the administrative and clinical workload associated with screening potential convalescent plasma donors experienced by transfusion staff at the Mayo Clinic Blood Donor Center. Thus, the blood donation team was able to continue collecting apheresis platelet, platelets, and whole blood donations while also scaling up convalescent plasma donations during the ongoing pandemic.

3) The simple web-based screening survey optimized volunteer convenience and the screening algorithm enabled rapid identification of currently eligible volunteers, retained interested volunteers that were not eligible upon initial survey completion, and provided a new call to action for those that did not meet convalescent plasma donation eligibility criteria -perform a standard blood donation, if eligible. 

Our strategy for interfacing with the community of COVID-19 survivors may be expanded through the following avenues: 1) By introducing plasma fractionators into our recruitment network, we may recruit donors to contribute to a hyperimmune IgG product for COVID-19. Two important populations of eligible donors would be immediate candidates for the plasma fractionation route: i) individuals that have antibody titers below the threshold thought to be efficacious for COVID-19 treatment and ii) volunteers ineligible for standard blood donation, such as multiparous women with Human Leukocyte Antigen antibodies.

2) There is the opportunity to leverage electronic medical records to, upon a positive COVID-19 test result, automatically alert the ordering physician to provide the patient with the link to our donor recruitment survey and support center email address. As the availability of serological tests increases, this avenue will enhance the volume of donors that did not receive an initial diagnostic test. survivors. Based on the responses to three key questions within the convalescent plasma donor recruitment survey -regarding COVID-19 laboratory test result, COVID-19 symptomology, and current residence -our team delineated interested volunteers into four categories: i) immediately eligible, ii) soon to be eligible, iii) eligible for other efforts, and iv) ineligible. Regardless of the categorization, all respondents authorizing follow-up interactions were contacted by our team of physician navigators or an automatically generated email to engage in additional COVID-19 related donor screening or to initiate a new call to action for blood or convalescent plasma donation. Expanded details are available in DONOR RECRUITMENT STRATEGY OVERVIEW.

J o u r n a l P r e -p r o o f 

USA Facts. Coronavirus Locations: COVID-19 Map by County and State

Remdesivir for the treatment of Covid-19-preliminary report

Dexamethasone in hospitalized patients with Covid-19-preliminary report

Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment?

Return to the past: the case for antibody-based therapies in infectious diseases

The convalescent sera option for containing COVID-19

Convalescent Plasma in 5,000 Patients

Deployment of convalescent plasma for the prevention and treatment of COVID-19

Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019

Treatment of 5 critically ill patients with COVID-19 with convalescent plasma

COVID-19 Convalescent Plasma: Now Is the Time for Better Science

Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial

Convalescent plasma treatment of severe COVID-19: A matched control study. medRxiv

Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support

The REDCap consortium: Building an international community of software platform partners

Convalescent Plasma


