On March 24, 2020, the US Food and Drug Administration announced an investigational initiative to transfuse convalescent plasma (CCP) from patients recovered from coronavirus disease 2019 (COVID‐19) to treat patients suffering from severe COVID‐19. 1 Initial eligibility criteria required donors to have evidence of past severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection as determined by a positive molecular diagnostic test of upper respiratory sample (ie, nasopharyngeal [NP] swab), blood positive for SARS‐CoV‐2 RNA, or a positive serologic test. 1 Minimum antibody titers or evidence of neutralizing antibodies were reported if testing was able to be performed but was not required with sample storage for future testing. 2 Donors also needed to be at least 14 days from resolution of clinical symptoms and had to meet allogeneic blood donor criteria per the Code of Federal Regulations. 2
The American Red Cross (ARC) mobilized CCP collection efforts at the end of March 2020. Serologic testing for antibodies to the SARS‐CoV‐2 spike glycoprotein using a semiquantitative enzyme‐linked immunosorbent assay (VITROS Anti‐SARS‐CoV‐2 Total Test; Ortho Clinical Diagnostics, Raritan, New Jersey) was instituted for CCP donors on 27 April 2020. 3 After implementation, only units from donors with a signal‐to‐cutoff (S/CO) ratio of 1.0 or greater (reactive per package insert) were labeled as CCP units. 3
The ARC had an evolutionary approach to donor qualification. At first, an initially positive NP swab (or a physician's attestation) with date of symptom resolution were required. Donors 14 to 28 days from symptom resolution required a follow‐up negative NP swab. Following serologic testing implementation, the ARC transitioned to qualifying donors without requiring diagnostic test proof, allowing donors to self‐report previous diagnostic testing positivity. All donors needed to have had a symptomatic COVID‐19 infection and be at least 14 days from symptom resolution.
Between 27 March and 14 May, 67 810 potential CCP donors registered via the ARC Web site; 38 085 (56%) acknowledged either an existing diagnostic COVID‐19 polymerase chain reaction (PCR) or serologic test. The remainder did not have a diagnostic test (i.e., PCR or serologic) reporting presumptive clinical COVID‐19 diagnosis only. Ortho Diagnostics VITROS Anti‐SARS‐CoV‐2 results were available for 325 CCPs at the time of analysis: 77 donors with only a clinical COVID‐19 diagnosis with the majority more than 28 days from symptom resolution, 62 donors with diagnostic testing and 14 to 28 days from symptom resolution, and 186 with diagnostic testing and more than 28 days from symptom resolution. A total of 36.4% of donors without diagnostic testing had a reactive VITROS test, with an overall median S/CO of 0.11 (Table 1). Among the donors with diagnostic testing, the early recovery group had 82.3% reactivity (overall median S/CO, 26.2). Those further in recovery had 91.9% (overall median S/CO, 129.5). Statistically, by χ 2 analysis, the percentage of donors with reactivity was significantly different among the three groups (P < .0001), and Kruskal‐Wallis tests demonstrated statistical significance in S/CO values among the groups (P < .0001).
TABLE 1.
Donor Testing Information
| CCP donation date range | % > 28 days from symptom resolution | % with reactive VITROS | Median S/CO (IQR) | |
|---|---|---|---|---|
| Donors without diagnostic testing (N = 77) | 4 May 2020 to 25 May 25, 2020 | 97.4 | 36.4 | 0.11 (32.05) |
| Donors with diagnostic testing and 14‐28 days symptom resolution (N = 62) | 8 April 2020 to 19 April 2020 | 0 | 82.3 | 26.20 (58.09) |
| Donors with diagnostic testing and > 28 days symptom resolution (N = 186) | 9 April 2020 to 19 May 2020 | 100 | 91.9 | 129.50 (210.80) |
| P | <.0001 | <.0001 | <.0001 |
CCP, convalescent plasma; IQR, interquartile range; S/CO, signal‐to‐cutoff.
Our seroreactivity evaluation in CCP donors presenting with and without a diagnostic COVID‐19 PCR test highlights the importance of testing to enrich for donors with SARS‐CoV‐2 antibodies. There were a few notable limitations to our study, including screening with only one testing platform examining a single immune response target to SARS‐CoV‐2 infection. This was a small study with a limited number of donors. The three groups were in different states of recovery but in this cohort, lack of diagnostic testing had the most pronounced effect on seroreactivity. Finally, this represents the experience of a single, large blood collector. Due to limitations of collection capacity, it is important to ensure the CCP population is likely to be COVID‐19 antibody enriched. This information may be of value to other CCP collectors recruiting CCP donors and building inventory.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
REFERENCES
- 1. Recommendations for Investigational COVID‐19 Convalescent Plasma, the Food and Drug Administration. https://www.fda.gov/media/141480/download. Accessed August 25, 2020.
- 2. Code of Federal Regulations . Title 21, CFR Parts 600 to 799. Washington, DC: US Government Printing Office, 2019 (revised annually).
- 3. Ortho Clinical Diagnostics . VITROS immunodiagnostic products anti‐SARS‐CoV‐2 Total reagent pack and VITROS immunodiagnostic products anti‐SARS‐CoV‐2 Total calibrator instructions for use. Version 3.0. Rochester, NY: Ortho Clinical Diagnostics, Inc, 2020. [Google Scholar]