How do I… facilitate a rapid response to a public health emergency requiring plasma collection with a public–private partnership?

Abstract

In March 2020, there were no treatment options for COVID-19. Passive immune therapy including anti-SARS-CoV-2 hyperimmune globulin (hIVIG) was a logical candidate for COVID-19 therapeutic trials, given past success treating emerging pathogens with endogenous neutralizing antibodies. We established a plasma collection protocol for persons recovered from COVID-19. To speed recruitment in the first U.S. hotspot, Seattle, Washington, federal and state public health agencies collaborated with Bloodworks Northwest to collect convalescent plasma (CP) for manufacturing hIVIG. During March–December 2020, we identified and recruited prospective CP donors via letters to persons recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection. Prospective donors were pre-screened and administered a medical history survey. Anti-SARS-CoV-2 neutralizing antibody (NAb) titers were classified as qualifying (≥1:80) or non-qualifying (<1:80) for enrollment based on a live virus neutralization assay. Generalized estimating equations were used to identify characteristics of donors associated with qualifying versus non-qualifying NAb titers. Overall, 21,359 letters resulted in 3207 inquiries, 2159 prescreenings with laboratory-confirmed SARS-CoV-2 infection, and 573 donors (27% of all pre-screenings with confirmed infection) who provided a screening plasma donation. Of 573 donors screened, 254 (44%) provided plasma with qualifying NAb titers, resulting in 1284 units for hIVIG manufacture. In a multivariable model, after adjusting for other factors, time (60 days) from COVID-19 symptom onset to screening was associated with lower odds of qualifying NAb (adjusted odds ratio = 0.67, 95% CI: 0.48–0.94). The collaboration facilitated a rapid response to develop and provide hIVIG for clinical trials and CP for transfusion. Only 1 in 12 donor inquiries resulted in a qualifying plasma donation. Challenges included recruitment and the relatively low percentage of persons with high NAb titers and limited screening capacity. This resource-intensive collaboration may not be scalable but informs preparedness and response strategies for plasma collection in future epidemics. Operational readiness plans with templates for screening, consent, and data collection forms are recommended.

1 |. BACKGROUND

As of June 2021, severe acute respiratory virus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected more than 30 million people in the United States, with more than 500,000 deaths and nearly 2 million hospitalizations.¹ Treatment options at the onset of a pandemic with a novel pathogen such as SARS-CoV-2 were limited, making passive immune therapy a reasonable choice for clinical trials. The U.S. Department of Health and Human Services (HHS) declared a public health emergency on January 31, 2020,² then on March 27, 2020 authorized the development, manufacturing, and emergency use of drugs and biological products including novel therapeutics.³ Among these therapeutics were two plasma-derived treatments, COVID-19 hyperimmune globulin (hIVIG) and COVID-19 convalescent plasma (CP).

Prior studies have investigated the use of CP as a treatment option for patients critically ill with other coronaviruses^4,5 and H1N1 influenza virus infections.^6,7 Studies conducted in China suggested that high antibody titer COVID-19 CP could reduce viremia and improve clinical symptoms.^8,9 Data from past viral epidemics on treatment with hIVIG, an injectable concentrated and purified product with standardized IgG neutralizing antibody (NAb) dosing, suggested improved benefits compared to CP transfusion. These potential benefits included use of a standardized product and increased safety, potency, reproducibility, efficiency of manufacture and distribution, clinical utility, as well as possibly improved clinical outcomes including reduced mortality, especially if given early in disease before onset of a poorly regulated inflammatory response and production of endogenous antibodies.^10,11

Given the limited therapeutic options and the anticipated benefit of hIVIG for transfusion, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) developed a protocol to screen persons recovered from COVID-19 to expedite clinical trials of hIVIG.¹² CDC was already working to contain COVID-19 in the first U.S. hotspot and had protocols in place to transmit case data securely between CDC and state and local health departments, so it offered assistance in communication with recovering COVID-19 patients. The protocol implementation plan included (1) identification of persons recovered from COVID-19, and referral to blood collection organizations (BCOs) for plasmapheresis donation; (2) infrastructure to test donor plasma for SARS-CoV-2 neutralizing antibody titers (NAb); and (3) approval and implementation of a clinical protocol. At the same time, BCOs independently worked with the U.S. Food and Drug Administration (FDA) to collect CP for transfusion, first for extended access investigational new drug applications for fully qualified plasma donations with special history characteristics, then emergency use authorization (EUA) after August 23, 2020.¹³

1.1 |. Initiating collaboration

Prior to the COVID-19 pandemic, there was no precedent for large-scale production of hIVIG at scale to supply clinical trials during an ongoing pandemic.^6,14 To support the hIVIG clinical trials, we rapidly established a public-private collaboration between a BCO (Bloodworks Northwest [BWNW]), the Washington State Department of Public Health (WADOH), CDC, and the NIAID to identify and characterize CP donors. The Seattle/King County metropolitan area was selected because it was the site of the first recognized case of COVID-19 in the U.S. and provided a population of potential donors. The region had over 1000 laboratory-confirmed cases by the end of March 2020.^1,15 The primary objective was to collect plasma to be used for hIVIG production for study in NIH planned clinical trials, and the secondary objective was characterization of donors. Here, we describe our efforts to recruit qualified patients and collect plasma for the manufacture of hIVIG (Figure 1).

FIGURE 1.

Flow diagram of recruitment of prospective convalescent plasma donors and data inclusion for analysis from persons reported by Washington State Department of Health to have recovered from COVID-19—King County, Washington, March 26–December 2, 2020.

*The total number of mailing recipients reflects outreach from three bulk mailings of 1474 letters (March 27–28, 2020), and 17,885 letters (July 23–August 7, 2020), and 2000 letters (September 14–30, 2020). Of the 1474 letters in the first mailing, 37 letters were sent back as undeliverable (97% received). No response or return rate data are available for the two subsequent mailings. This study did not use direct advertising. Donors who completed the prescreening form and did not report a history of a COVID-19 diagnosis and/or positive diagnostic test for SARS-CoV-2 presented via word of mouth, media reports, referrals, etc.

^†107 donors donated plasma to both the hIVIG and CP for transfusion stockpiles.

^§Donor plasma samples were screened for anti-SARS-CoV-2 spike protein neutralizing antibody (NAb) titer quantification using a 2-fold serial dilution from 1:40–1:1280. Results were reported as the highest dilution of plasma leading to at least 50% reduction in SARS-CoV-2 titers.

^¶Anti-SARS-CoV-2 neutralizing antibody (NAb) titers were classified as qualifying (≥1:80) or non-qualifying (<1:80) for enrollment based on a live virus neutralization assay.

Several challenges were identified in implementing the NIH plasma collection protocol at the onset of the pandemic: identification and recruitment of qualified CP donors, validation of donor eligibility, donor intake and screening capacity, and ability to conduct neutralization assays (the gold standard for SARS-CoV-2 antibody quantification). WADOH provided donor contact information, records on laboratory confirmation of SARS-CoV-2 infection in persons recovered from COVID-19 via nucleic acid analysis, and assistance with donor outreach, recruitment, and validation. CDC aided with donor outreach, recruitment, validation, and characterization. The Integrated Research Facility (IRF) at the NIAID developed and conducted live virus NAb assays on plasma collected from donors by BWNW.¹⁶ BWNW coordinated human subjects regulatory requirements, donor intake, screening and blood collection, processing, and shipping of plasma. Institutional review board approval was obtained through Advarra. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.¹

1.2 |. Identifying and recruiting donors

Per the NIH protocol, eligible donors were aged 18–70 years, recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection, and were free of symptoms for 28 days or more.

In March 2020, CDC and WADOH sent joint letters of invitation to prospective plasma donors using WADOH public health registries of COVID-19 patients, followed by a joint press release in April 2020 intended to notify the public of this activity.¹⁷ Active donor recruitment by WADOH occurred from March 27 to September 30, 2020. Collections began on April 10, 2020 and continued until November 16, 2020. Screening and collection operations at BWNW and NIAID formally concluded on December 16, 2020.

1.3 |. Prescreening and validating donors

BWNW initiated a secure electronic online prescreening system, consisting of a questionnaire to collect and assess demographic information and a data field to self-report clinical history of prior COVID-19 infection. Donors confirmed history of laboratory-confirmed SARS-CoV-2 and recovery from COVID-19, defined as complete resolution of symptoms at least 28 days prior to donation.

BWNW lacked access to health records to validate prospective donors’ prior COVID-19 infections. To make data collection more efficient, BWNW collaborated with WADOH and CDC to validate a SARS-CoV-2 test result in individuals who self-reported a prior COVID-19 infection. BWNW staff contacted donors with validated testing histories and maintained records of communication with donors.

1.4 |. Screening donors for anti-SARS-CoV-2 antibodies

Prescreened, validated donors were invited to schedule a screening appointment at BWNW. Eligible donors provided informed consent prior to proceeding with study procedures. At screening appointments, BWNW confirmed prospective donors met FDA/AABB standard donor^2,3 and/or plasmapheresis⁴ requirements, then eligibility for plasma donation for the NIH hIVIG study. Per the NIH protocol, donors were required to have an anti-SARS-CoV-2 antibody titer of 1:80 or greater to qualify for plasma collection for hIVIG, so donors provided a blood sample to assess anti-SARS-CoV-2 antibody levels. On April 10, 2020, BWNW began screening validated donors for NAb titer testing for CP and hIVIG manufacture. Validated donors received a $60 reimbursement for attending the screening visit. Prior to donation, donors completed a survey instrument (Appendix S1) assessing demographics, clinical, and past medical history. Approximately 35 ml of blood was collected from donors and processed. BWNW performed routine infectious diseases screening⁵ in accordance with FDA^6,7 and AABB guidance,^8,9 then shipped processed samples to NIAID for NAb titer assays.

1.5 |. Collecting plasma from donors

Qualified volunteer plasma donors provided 600–800 ml per plasmapheresis collection, a mean 3.7 units per donation (200–250 ml per unit).

In addition to NAb testing at NIAID Integrated Research Facility (IRF), all units were subjected to anti-SARS-CoV-2 ELISA (IgG) antibody testing (EUROIMMUN, Mountain Lakes, NJ).

1.6 |. Quantitating NAb

Plasma samples were sent to NIAID IRF (Fort Detrick, Maryland) for NAb titer quantification using a fluorescence reduction neutralization assay (FRNA) with SARS-CoV-2 isolate WA-01/2020 provided by CDC.¹⁸ Plasma was screened using a 2-fold serial dilution from 1:40 to 1:1280. Results were reported as the highest dilution of plasma leading to at least 50% reduction in SARS-CoV-2 titers, not quantitated at the limit of detection (NT50 at a minimum dilution of 1:40) nor for intermediate titer levels (1:60, 1:80). Titers <1:40 were reported as undetectable. Time from collection to receipt of sample was a median of 2 days and mean of 3.24 ± 3 days. There was a median of 10 days from receipt to NAb titer result. Donor NAb titers were classified as qualifying, ≥1:80 (April–July 2020), or non-qualifying <1:80. Qualifying donors were solicited for repeat collections. After a study protocol modification to increase repeat donations, donors with NAb ≥1:40 could return for an additional screening donation (July–November 2020).

Criterion for CP to qualify for hIVIG manufacturing was NAb titer >1:40 (i.e., 1:80 or above, with 1:40 defined as acceptable in the event an alternative matched unit was unavailable). Non-qualifying donations were diverted to the standard blood supply. To assess characteristics of donors with qualifying (≥1:40) or non-qualifying (<1:40) NAb titers and adjust for repeated donations from the same individual over time, generalized estimating equations were used with a binomial distribution and an autoregressive correlation structure controlling for age, sex, race, previous history of a COVID-19 hospitalization, time (60 days) between COVID-19 symptom onset, and comorbidities. All statistical analyses were performed using the R statistical programming language (v. 4.0.3, R Foundation for Statistical Computing, 2020) and using various packages, including the geepack for generalized estimating equations (R Core Team 2020. R: A language and environment for statistical computing).

Study data were collected and managed using REDCap electronic data capture tools hosted at the NIAID. REDCap (Research Electronic Data Capture) is a secure, web-based software platform designed to support data capture for research studies, providing an intuitive interface for validated data capture; audit trails for tracking data manipulation and export procedures; automated export procedures for seamless data downloads to common statistical packages; and procedures for data integration and interoperability with external sources.

2 |. RESULTS

Overall, 21,359 prospective donors were sent letters of invitation to donate CP and 3207 (15%) completed prescreening (Figure 1). On average, recruitment of prospective donors took approximately 1–2 weeks from sending the letter of invitation to validation. Of the 3207 pre-screened prospective donors, 2159 (67%) had laboratory-confirmed SARS-CoV-2 infection. Of the 2159 with laboratory-confirmed SARS-CoV-2 infection, 573 (27%) donors provided NAb screening titers, of which less than half (254; 44%) had a qualifying titer. These 254 donors each donated one or more times, for a total of 345 CP collections yielding 1284 qualifying CP units for manufacturing into hIVIG. During the pandemic, a parallel and competing need for CP for transfusion emerged. Additional donors provided 1104 CP collections for transfusion producing 3470 CP units for transfusion.

Characteristics of donors with qualifying and non-qualifying CP are shown in Table 1. Three-quarters of donors were White. Qualifying NAb donors reported a median of 73 days (interquartile range [IQR]: 54–151 days) from COVID-19 symptom onset to screening compared to 103 days (IQR: 66–162 days) for non-qualifying NAb donors. Over a third of qualifying donors were classified as obese (body mass index ≥30 kg/m²). Results from the multivariate generalized estimating equations model comparing donors with qualifying and non-qualifying CP are shown in Figure 2. Characteristics in the model positively associated with qualifying titers were age 50–64 years (adjusted odds ratio [aOR] = 2.39, 95% CI 1.15–4.96) or ≥65 years (aOR = 4.45, 95% CI 1.82–10.87) relative to 19–34 years, history of obesity (aOR = 1.90, 95% CI 1.10–3.30), or COVID-19 related hospitalization (aOR = 5.23, 95% CI 1.98–13.83) (Figure 2). After adjustment for age, sex, race/ethnicity, COVID-19 hospitalizations, and comorbidities, time (60 days) between COVID-19 symptom onset and screening was inversely associated with high titers (aOR = 0.67, 95% CI 0.48–0.94), indicating plasma collected earlier following recovery had greater odds of having qualifying NAb titers. Longer time from COVID-19 symptom onset to screening was associated with lower odds of qualifying NAb.

TABLE 1.

Demographic and clinical characteristics of Bloodworks Northwest COVID-19 convalescent plasma donors—King County, Washington, April–November 2020

Characteristic	No. (%)
	Qualifying titera (n = 254)	Non-qualifying titer (n = 319)
Sex
Male	122 (48)	189 (59)
Female	123 (48)	106 (33)
Unknown	9 (4)	24 (8)
Age, years
19–34	20 (8)	63 (20)
35–49	37 (15)	66 (21)
50–64	71 (28)	87 (27)
≥65	33 (13)	25 (8)
Unknown	93 (37)	78 (25)
Race
White	189 (74)	247 (77)
Asian	13 (5)	4 (1)
Black	4 (2)	10 (3)
American Indian/Alaska Native	14 (6)	12 (4)
More than one race	8 (3)	13 (4)
All other races	10 (4)	9 (3)
Unknown/not reported	16 (6)	24 (8)
Symptom onset to screening, median days (IQR)b	73.0 (54–151)	102.5 (66–162)
Unknown screening date	65 (26)	0
COVID-19 related hospitalization	37 (15)	7 (2)
Unknown/not reported	17 (7)	9 (8)
Body mass indexc
Mean (SD)	27.5 (6.3)	25.7 (5.6)
Unknown height or weight	15 (6)	16 (5)
Obese, body mass index ≥30	84 (35)	65 (22)
Smoker, yes	6 (2)	7 (2)
Pre-existing or past medical conditiond
Diabetes	22 (9)	7 (2)
Hypertension	43 (17)	27 (9)
Cancer	16 (6)	12 (4)
Chronic lung disease	11 (4)	10 (3)
Chronic heart disease	3 (1)	8 (3)
Chronic liver disease	1 (<1)	1 (<1)
Chronic kidney disease	4 (2)	5 (2)

^aAnti-SARS-CoV-2 neutralizing antibody (NAb) titers were classified as qualifying (≥1:80) or non-qualifying (<1:80) for enrollment based on a live virus neutralization assay.

^bSelf-reported symptom onset.

^cBody mass index was calculated using the formula: weight (pounds)/[height (inches)]² × 703.

^dProspective donors were asked whether they had ever been diagnosed with any of the following: diabetes, hypertension, cancer, chronic lung disease, chronic heart disease, chronic liver disease, chronic kidney disease. Comorbidities were captured as yes only responses, so it was not possible to accurately assess the frequency of no versus missing responses.

FIGURE 2.

Results of multivariate generalized estimating equation model with adjusted odds ratios^† (95% confidence interval) comparing donor characteristics associated with qualifying neutralizing antibody titers to donors with non-qualifying neutralizing antibody titers—King County, Washington^§

*Generalized estimating equations were used with a binomial distribution and an autoregressive (AR-1) correlation structure controlling for age, sex, race, previous history of a COVID-19 hospitalization, time (60 days) between COVID-19 symptom onset, and comorbidities. Organ dysfunction was classified as the combined binary response of any of the following: chronic lung, heart, liver, or kidney disease (Table 1). After removing missing values for demographic and clinical information, the model was run on n = 321 individuals. Statistical analyses were performed using R v. 4.0.3, including the geepack for generalized estimating equations (R Core Team 2020).

^†For adjusted odds ratios, the reference age group was donors aged 19–34 years. The reference race was White.

^§Donors were recruited beginning March 26, 2020, with earliest date of SARS-CoV-2 positive diagnostic test on February 26, 2020. Donor recruitment ended November 16, 2020.

3 |. DISCUSSION

Donor recruitment for convalescent plasma is difficult, particularly in the setting of an unprecedented global public health emergency. This public-private health collaboration aimed to accelerate and facilitate donor recruitment and characterize plasma donors for rapid manufacture of hIVIG. Overall, this collaboration exceeded initial collection projections of ∼600 units (150 L) for hIVIG and provided important insight and lessons for future pandemic preparedness.

The collaboration had several strengths. First, we leveraged the expertise of public agencies and a BCO to develop and rapidly implement a plasma collection protocol. The protocol was written and approved in a short time window. Second, the collaboration promoted altruistic blood donation in a local community and facilitated donor recruitment for CP collections¹⁹ that resulted in collection of 4754 units of CP. Finally, the collaboration between governmental and nongovernmental partners resulted in agile and rapid modification of clinical and operational protocols to meet evolving needs.

The collaboration also had significant challenges. These included timely implementation of a protocol and conversion of screening and collection capability to scaling for special collections. In the early months of the pandemic, BWNW needed to rapidly and iteratively develop and modify protocols and informed consent materials with NIH. Managing the competing priorities (i.e., plasma for hIVIG vs. CP for transfusion) required balancing immediate community needs with research commitments. Assimilation of an evolving evidence base into BWNW’s closely regulated collection system required novel approaches. Challenges with donor outreach strained resources and reduced operational efficiency.

These activities were further challenged by limitations in the development and implementation of national plasma collection strategies which would have ideally resulted in more efficient allocation of collected plasma for hIVIG manufacturing along with transfusion. In the absence of such a strategy, demand for plasma for transfusion led to a delay in direction of collected plasma for hIVIG production. Additionally, early in the pandemic, the efficacy of CP for transfusion was unclear. NAb titers were not routinely measured nationally, limiting the ability to study the clinical impact of this therapy.^20,21 Where titers were measured, the use of different assays and the lack of delivery protocols slowed standardization and assessment of CP products. Despite these factors, CP was widely adopted into practice despite lack of evidence of improvement of clinical outcomes, which precluded a rigorous assessment of efficacy of CP and hIVIG. Attempts to conduct CP clinical trials detracted from development of hIVIG products. Due to the inherent variability of neutralizing antibody concentration in individual convalescent plasma units versus standardized concentration of neutralizing antibodies in hIVIG, future emergency research response in an outbreak to assess the clinical benefit of passive antibody should prioritize the manufacturing and testing of hIVIG through randomized clinical trials of hIVIG rather than trials of convalescent plasma.

To date, thousands of CP units and comparatively few doses of hIVIG have been used. Distribution of new and stockpiled CP units exceeded collections by over 7000 units in fall and winter 2020.²² While high-titer CP for the treatment of hospitalized patients with COVID-19 may be used early in the course of disease, this modality has no clinical benefit when used later.^23,24 NAb titers of CP collected from a single donor vary over time; as such, the EUA was revised in February 2021 to limit the authorization to the use of high-titer CP.²⁵ While hIVIG was hoped to be a more efficacious treatment, the Phase 3 Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) did not meet clinical endpoints in hospitalized patients. The trial found no evidence that hIVIG caused detrimental impact to the patients. RCTs of hIVIG for the treatment of COVID-19 outpatients are ongoing. The discrepancy in clinical trial activity and data collection for the two treatments highlights the importance of RCTs in pandemics despite the considerable demand that might arise for routine clinical care among ill patients. Since the launch of this study, more has been learned about the importance of collecting sequencing data to track neutralizing capacity against SARS-CoV-2 variants (e.g., to determine candidacy for monoclonal antibody therapies). Future collaborations should include testing and trial infrastructure to track variants to ensure rapid availability of effective and appropriate allocation of medical countermeasures to patients.

The activities of this partnership demonstrated how important it is to establish adaptable protocols, collaborations, management, and leadership prior to the next pandemic. Strong leadership is essential to an agile response that can meet rapidly changing needs, such as data sharing needs. This study recruited donors from early iterations of COVID-19 public health case registries via letter of invitation from CDC and WA DOH leads (Figure 1). Case registries could hypothetically improve return in a shorter time frame than would be achievable using standard recruitment mechanisms unassisted by government. It may be feasible to improve return and get rapid access to patient data using public health case registries on an ongoing basis, although this study did not track methods of referral, nor did it compare use of letters of invitation versus electronic communications from BCO marketing and outreach.

To bypass delays associated with the complicated logistics of data sharing in the setting of the next pandemic, future best practices can be considered (Table 2). These proposed practices may provide a foundation for mounting a rapid, effective, coordinated national effort through public-private partnerships.

TABLE 2.

Recommendations to counter potential delays to mounting a coordinated, strategic national approach to emergency response and research in future epidemics

Stakeholders	Delays experienced in COVID-19 emergency response	Recommendations to improve pandemic response
Federala	No efficacious novel medical countermeasures were available at the time of the emergence of COVID-19
Federal State/Localb BCO’sc	Collection of hIVIG for clinical trials impeded by demand for convalescent plasma as therapeutic	Outline proposed use and deployment of biologics for multiple uses in future epidemics, strategizing and anticipating needs for biologics such as purified immune therapy/hIVIG Develop national pandemic readiness plans that incorporate detailed guidance on production, evaluation, and distribution of convalescent plasma • Prioritize clinical trials of hyperimmune globulin to provide rapid and accurate assessment of safety and efficacy of passive immune therapy • Include plasma collection strategies in national pandemic response strategy • Develop and implement national plasma collection strategies to guide more efficient use and allocation of collected plasma • Develop draft guidance for trials of biologic countermeasures including hIVIG to enable rapid evaluation of efficacy early in a relevant pandemic • Establish public-private/multisector collaboration and conduct table-top exercises for readiness and education • Include BCO’s as a stakeholder in pandemic preparedness and response trainings, preparation, and action plans and establish working relationships ahead of an emergency • Identify mechanisms of funding to support BCO’s in business transition to convalescent plasma collection
Federal State/Local BCO’s	Blood centers lacked the infrastructure, expertise, and systems required for identification of COVID-19 survivors and large-scale convalescent plasma collection for clinical trials	Improve BCO’s operational readiness requirements in a pandemic • Operational readiness training • Develop Federal-State-BCO data-sharing systems to enable donor identification • Develop pandemic emergency donor recruitment, marketing, and collection protocols, tools, materials • Train BCO’s for pandemic readiness • Co-develop (NIH and BCOs) protocols, templates, informed consent, and IRB materials that can be rapidly adapted, modified, iterated, submitted, and implemented at the onset of a pandemic • Establish strong collaborations to lay the groundwork for just-in-time pandemic requirements • Develop in advance financial compensation/budgets for BCO’s that will provide necessary resources for their participation in collection, screening, and scaling, including reimbursement of BCO’s for plasma collection costs
Federal BCO’s	Serologic testing was not immediately available to blood centers, but was implemented several months after the development of these assays	• When relevant (depending on pathogen), expedite development and approval of novel serology and NAAT assays required for blood qualification • Develop data collection and sharing capabilities for rapid evaluation and monitoring of serology tests across sites • Develop testing and trial infrastructure to perform genetic sequencing, including information on genetic variants that may impact neutralizing capacity of plasma product • Formalize mechanisms for rapid data sharing and information dissemination

^aFederal agencies

^bState and local health departments

^cBlood collection organizations

In future epidemics, it will be imperative to integrate clinical research if plasma collection is considered for therapeutic purposes. We recommend providing BCOs and public health partners with operational readiness plans. Plans could include templates for consent forms and protocols for prescreening, screening, collection, evaluation, and data sharing. Training could include how to rapidly deploy remote and automated processes to facilitate donor intake using customizable, interoperable technology platforms. Pandemic preparedness should ensure that collaborators have parallel capacities in place at the onset of an outbreak. Some aspects of pandemic preparedness like rapid development and approval of reliable serology assays for new pathogens are difficult to bring to scale, but they present challenges to efficacious plasma collection for trials and should have high priority.

Abbreviations:

BCO

blood collection organization

BWNW

Bloodworks Northwest Research Institute

CDC

United States Centers for Disease Control and Prevention

CP

COVID-19 convalescent plasma

EUA

emergency use authorization

FDA

United States Food and Drug Administration

HHS

United States Department of Health and Human Services

hIVIG

COVID-19 hyperimmune globulin

IND

investigational new drug

NAb

neutralizing antibody titer (antibody to the SARS-CoV-2 spike protein)

NIAID

National Institute of Allergy and Infectious Diseases, National Institutes of Health

WADOH

Washington State Department of Health