Administration of high titer convalescent anti-SARS-CoV-2 plasma: From donor selection to monitoring recipient outcomes

Abstract

Early in the SARS-CoV-2 pandemic, convalescent plasma (CP) therapy was proposed as a treatment for severely ill patients. We conducted a CP treatment protocol under the Mayo Clinic Extended Access Program at University Hospital Brooklyn (UHB). Potential donors were screened with a lateral flow assay (LFA) for IgM and IgG antibodies against the SARS-CoV-2 S1 receptor-binding domain (RBD). Volunteers that were LFA positive were tested with an ELISA to measure IgG titers against the RBD. Subjects with titers of at least 1:1024 were selected to donate. Most donors with positive LFA had acceptable titers and were eligible to donate. Out of 171 volunteers, only 65 tested positive in the LFA (38.0%), and 55 (32.2%) had titers of at least 1:1024. Before our donation program started, 31 CP units were procured from the New York Blood Center (NYBC). Among the 31 CP units that were obtained from the NYBC, 25 units (80.6%) were positive in the LFA but only 12 units (38.7%) had titers of at least 1:1024. CP was administered to 28 hospitalized COVID-19 patients. Patients who received low titer CP, high titer CP and patients who did not receive CP were followed for 45 days after presentation. Severe adverse events were not associated with CP transfusion. Death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality, than patients that received low titer CP (≤1:1024) 77.8% mortality.

HLA B53 is associated with a poor outcome in black COVID-19 patients

“…For comparative purposes HLA typing was also performed on 40 convalescent plasma (CP) donors who had had mild COVID-19 symptoms, were never hospitalized and volunteered to donate CP. Inclusion criteria for CP donors was a previous positive RT-PCR test for SARS-CoV-2 and/or detectable antibodies to SARS-CoV-2 of either the IgM type, IgG type or both [18] . HLA typing of 40 CP donors for the A, B, C, DRB1, 3, 4, 5, DQA, DQB, DPA and DPB loci is shown in Supplementary Table 3 .…”

“…The Downstate Institutional Review Board (IRB) reviewed and approved the studies in this report (IRB #1232938-3 and IRB #341403-1). Characteristics of patients given CP and those not given CP as well as CP donor characteristics were previously published [18] .…”

“…Sixty-five (38.0%) tested positive for IgG and their anti-SARS-CoV-2 RBD IgG titer, determined by enzyme-linked immunosorbent assay (ELISA), was considered of sufficient strength to be a CP donor. Demographic characteristics of volunteers screened for possible CP donation are provided in our previous publication [18] . Genomic DNA was available from 40 of the 65 anti- RBD positive plasma donors for HLA typing in the CLIA certified UHB Transplant Immunology & Immunogenetics Laboratory by rSSO / Luminex technology (Immucor, Norcross, GA).…”

“…We hypothesized that in Blacks, an increased risk for severe COVID-19 may be due, in part, to the prevalence of HLA allele(s) that not only binds a SARS-CoV-2 peptide but may bind a self-peptide as well. In the current investigation, we determined the HLA type of a cohort of hospitalized COVID-19 patients at UHB [18] . We compared their HLA types to a cohort that had mild COVID-19 symptoms and had volunteered to donate convalescent plasma (CP) to critically ill COVID-19 patients under the Mayo Clinic Convalescent Plasma Treatment Program [19] .…”

Convalescent plasma for coronavirus disease 2019: Dose is the key

“…[15][16][17] Mendoza found that death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality than patients that received low titer CP (1:1024) 77.8% mortality. [18] The volume of plasma that should be administered per kg of body weight depends on the antibody titer. For instance, 5 mL/kg plasma is required with an antibody titer ≥1:160.…”