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HLA Antibody Rates Are Not Increased in a Regional Group of Male COVID-19 Convalescent Plasma Donors

      To The Editor:
      Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) remains a widely used therapeutic option for patients hospitalized for COVID-19 as further variant strains continue to arise. We recently reported significantly elevated positivity rates (P < .0001) for HLA antibodies (HLA-Abs), a risk factor for transfusion-associated acute lung injury, in 5 of 69 local male CCP donors (7.2 %).
      • Juskewitch J.E.
      • Stubbs J.R.
      • Gandhi M.J.
      Elevated rate of HLA antibodies in male COVID-19 convalescent plasma donors: a risk factor for transfusion-related acute lung injury.
      ,
      • Popovsky M.A.
      • Moore S.B.
      Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.
      As noted in a subsequent reply letter though, CCP has repeatedly exhibited a safety profile similar to standard plasma.
      • Franchini M.
      • Glingani C.
      Safety of convalescent plasma transfusion.
      ,
      • Joyner M.J.
      • Bruno K.A.
      • Klassen S.A.
      • et al.
      Safety update: COVID-19 convalescent plasma in 20,000 hospitalized patients.
      Because HLA-Ab screening is not routinely performed on male donors, it remains unclear whether male CCP donors truly have an elevated HLA-Ab screening positivity rate and pose a potential increased transfusion-associated acute lung injury risk to CCP recipients. In collaboration with several blood donation organizations, we assessed the prevalence of positive HLA-Ab screening results in male CCP donors across the southeastern United States.
      Male CCP donors who donated from April 27 through August 24, 2020, at Kentucky Blood Center, LifeSouth Community Blood Centers, Mississippi Blood Services, Shepeard Community Blood Center, and South Texas Blood & Tissue Center with sufficient residual serum and de-identified demographic data available were eligible for this cross-sectional study. All CCP donors provided permission to use de-identified donor information and serum samples for research. Given the de-identified nature of this study, clinical information on COVID-19 infection and past pregnancy, transfusion, or transplantation history was not available. Each male CCP serum sample was identified using the associated CCP unit’s ISBT 128 donation identification number. This study was approved by the local institutional review board.
      All CCP serum samples were screened for HLA-Abs using the same LABScreen Mixed Class I and Class II assays (One Lambda) and performed by the same American Society for Histocompatibility & Immunogenetics-accredited tissue typing laboratory that offers blood donor HLA-Ab screening.
      • Juskewitch J.E.
      • Stubbs J.R.
      • Gandhi M.J.
      Elevated rate of HLA antibodies in male COVID-19 convalescent plasma donors: a risk factor for transfusion-related acute lung injury.
      Positive screening cutoff ratios for these HLA-Ab screening assays (class I ratio, >30; class II ratio, >18) had been previously established by the laboratory using a +5SD mark in a population of male never-transfused blood donors following a published methodology.
      • Carrick D.M.
      • Norris P.J.
      • Endres R.O.
      • et al.
      National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study-II. Establishing assay cutoffs for HLA antibody screening of apheresis donors.
      Five hundred twenty-six male CCP donors with sufficient residual serum and de-identified demographic information available were screened for HLA-Abs (Figure). The median donor age at the time of CCP collection was 48.8 years (range, 16.0-85.5 years). Only 2 of 526 male CCP donors screened positive for HLA-Abs (0.3%) within the expected less than 1% screening positivity rate. These 2 male CCP donors screened positive only for class I HLA-Abs (class I ratios, 33.74 and 60.91), were collected at different blood donation organizations, and were older at CCP donation (age, 68.8 and 73.3 years) than most male CCP donors. The positivity rate in this male CCP donor population significantly differed from the previously reported 7.2% HLA-Ab screening positivity rate (Fisher exact, P=.001).
      Figure thumbnail gr1
      FigureDistribution map of coronavrius disease 2019 convalescent plasma (CCP) study samples.
      This larger cross-sectional study does not support an association between increased HLA-Ab screening positivity rates and recent COVID-19 infection in male CCP donors. These discrepant findings between these 2 male CCP groups may be due to time differences since donor COVID-19 infection or regional differences in infecting COVID-19 strains or may indicate a false-positive study result in our initial report.

      Acknowledgments

      We thank the faculty and staff of South Texas Blood & Tissue Center, LifeSouth Community Blood Centers, Shepeard Community Blood Center, Kentucky Blood Center, and Mississippi Blood Services for their work and support in this study. We also thank all the convalescent plasma (CCP) donors who volunteered throughout the coronavirus disease 2019 pandemic to provide CCP products as well as research samples and de-identified donor data for ongoing CCP research.

      References

        • Juskewitch J.E.
        • Stubbs J.R.
        • Gandhi M.J.
        Elevated rate of HLA antibodies in male COVID-19 convalescent plasma donors: a risk factor for transfusion-related acute lung injury.
        Mayo Clin Proc. 2021; 96: 500-502
        • Popovsky M.A.
        • Moore S.B.
        Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.
        Transfusion. 1985; 25: 573-577
        • Franchini M.
        • Glingani C.
        Safety of convalescent plasma transfusion.
        Mayo Clin Proc. 2021; 96: 1368-1369
        • Joyner M.J.
        • Bruno K.A.
        • Klassen S.A.
        • et al.
        Safety update: COVID-19 convalescent plasma in 20,000 hospitalized patients.
        Mayo Clin Proc. 2020; 95: 1888-1897
        • Carrick D.M.
        • Norris P.J.
        • Endres R.O.
        • et al.
        National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study-II. Establishing assay cutoffs for HLA antibody screening of apheresis donors.
        Transfusion. 2011; 51: 2092-2101