Impact of serological and PCR testing requirements on the selection of COVID-19 convalescent plasma donors

Abstract

Background: Convalescent plasma is undergoing randomized trials as a potential therapeutic option for COVID-19 infection. Little empirical evidence exists regarding the determination of donor eligibility and experiences with donor selection.

Study design and methods: This prospective study was conducted at a tertiary care hospital in New York to select plasma donors for a randomized, double-blind, controlled convalescent plasma trial. Clearance for donation required successful completion of an online questionnaire and an in-person screening visit, which included (a) completion of a Donor Health Questionnaire (DHQ), (b) Immunoglobulin G (IgG) antibody testing using an immunochromatographic anti- severe acute respiratory coronavirus 2 (SARS-CoV-2) test, (c) Polymerase chain reaction (PCR) testing if <28 days from symptom resolution, and (d) routine blood bank testing.

Results: After receiving 3093 online questionnaires, 521 individuals presented for in-person screening visits, with 40.1% (n = 209) fully qualifying. Subjects (n = 312) failed to progress due to the following reasons: disqualifying answer from DHQ (n = 30, 9.6%), insufficient antibodies (n = 198, 63.5%), persistent positive PCR tests (n = 14, 4.5%), and blood donation testing labs (n = 70, 22.4%). Importantly, 24.6% and 11.1% of potential donors who reported having PCR-diagnosed infection had low or undetectable SARS-CoV-2 antibody levels, respectively. Surprisingly, 62.9% (56/89) of subjects had positive PCR tests 14-27 days after symptom resolution, with 13 individuals continuing to be PCR positive after 27 days.

Conclusion: It is feasible for a single site to fully qualify a large number of convalescent plasma donors in a short period of time. Among otherwise qualified convalescent plasma donors, we found high rates of low or undetectable antibody levels and many individuals with persistently positive PCR tests.

Keywords: blood component preparations; donors; immunology (other than RBC serology).

FIGURE 1

Convalescent plasma donor eligibility screening steps (CONSORT). Shows screening steps from online survey through full qualification of donors

FIGURE 2

Distribution of immunoglobulin G (IgG) antibody levels to severe acute respiratory coronavirus 2 on initial screening visit. Potential donors (n = 505) were categorized by IgG nucleocapsid protein antibody level on the initial screening visit into four groups using criteria defined a priori: undetectable (<25 reflectance units, n = 88), low/insufficient (25‐144, n = 118), medium/adequate (145‐300, n = 168), and high/adequate (>300, n = 131) groups. IgG antibody levels are shown as median (orange circle) with interquartile range for each group [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Associations between screening characteristics and adequate antibody levels. An exploratory multivariable logistic regression model was trained to differentiate those donors with adequate antibody levels (defined as an immunoglobulin G antinucleocapsid level ≥ 145) from those with inadequate antibody levels at the initial testing. Characteristics from Table 1 were selected for inclusion based on univariate screening and final model fit. All final model variables and adjusted results are presented in the figure above. Final c‐Index = 0.753, Hosmer‐Lemeshow = 0.42, indicating a good model fit

FIGURE 4

Persistent polymerase chain reaction (PCR) positivity as a function of time since symptom resolution. Persistent PCR positivity is shown for the 40 potential donors who had a positive initial PCR test fewer than 28 days following substantive symptom resolution and at least one additional test result prior to the May 13th follow‐up date (database lock). Once a potential donor tested positive (red circle), he or she was required to have a negative PCR (green circle) prior to donation, regardless of the time since symptom resolution. Additional follow‐up testing is still required for nine potential donors who have not yet had a negative PCR test. Current Food and Drug Administration (FDA) guidance requires only that potential donors be symptom free for at least 14 days (dashed line, left) and does not require any PCR testing prior to donation. The April 8th FDA guidance previously required PCR testing for potential donors who were symptom free for fewer than 28 days (dashed line, right) [Color figure can be viewed at wileyonlinelibrary.com]