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Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

ABSTRACT: Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

SUBMITTER: Kunze KL

PROVIDER: S-EPMC8357797 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Kunze Katie L KL Johnson Patrick W PW van Helmond Noud N Senefeld Jonathon W JW Petersen Molly M MM Klassen Stephen A SA Wiggins Chad C CC Klompas Allan M AM Bruno Katelyn A KA Mills John R JR Theel Elitza S ES Buras Matthew R MR Golafshar Michael A MA Sexton Matthew A MA Diaz Soto Juan C JC Baker Sarah E SE Shepherd John R A JRA Verdun Nicole C NC Marks Peter P Paneth Nigel S NS Fairweather DeLisa D Wright R Scott RS van Buskirk Camille M CM Winters Jeffrey L JL Stubbs James R JR Senese Katherine A KA Pletsch Michaela C MC Buchholtz Zachary A ZA Rea Robert F RF Herasevich Vitaly V Whelan Emily R ER Clayburn Andrew J AJ Larson Kathryn F KF Ripoll Juan G JG Andersen Kylie J KJ Lesser Elizabeth R ER Vogt Matthew N P MNP Dennis Joshua J JJ Regimbal Riley J RJ Bauer Philippe R PR Blair Janis E JE Casadevall Arturo A Carter Rickey E RE Joyner Michael J MJ

Nature communications 20210811 1

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hyp ...[more]

PMID: 34381030

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Project description:BackgroundThe coronavirus disease-2019 (COVID-19) is a systemic disease with severe implications on the vascular and coagulation system. A procoagulant platelet phenotype has been reported at least in the acute disease phase. Soluble P-selectin (sP-sel) in the plasma is a surrogate biomarker of platelet activation. Increased plasma levels of sP-sel have been reported in hospitalized COVID-19 patients associated with disease severity. Here, we evaluated in a longitudinal study the sP-sel plasma concentration in blood donors who previously suffered from moderate COVID-19.Methods154 COVID-19 convalescent and 111 non-infected control donors were recruited for plasma donation and for participation in the CORE research trial. First donation (T1) was performed 43-378 days after COVID-19 diagnosis. From most of the donors the second (T2) plasma donation including blood sampling was obtained after a time period of 21-74 days and the third (T3) donation after additional 22-78 days. Baseline characteristics including COVID-19 symptoms of the donors were recorded based on a questionnaire. Platelet function was measured at T1 by flow cytometry and light transmission aggregometry in a representative subgroup of 25 COVID-19 convalescent and 28 control donors. The sP-sel plasma concentration was determined in a total of 704 samples by using a commercial ELISA.ResultsIn vitro platelet function was comparable in COVID-19 convalescent and control donors at T1. Plasma samples from COVID-19 convalescent donors revealed a significantly higher sP-sel level compared to controls at T1 (1.05 ± 0.42 ng/mL vs. 0.81 ± 0.30 ng/mL; p < 0.0001) and T2 (0.96 ± 0.39 ng/mL vs. 0.83 ± 0.38 ng/mL; p = 0.0098). At T3 the sP-sel plasma level was comparable in both study groups. Most of the COVID-19 convalescent donors showed a continuous decrease of sP-sel from T1 to T3.ConclusionIncreased sP-sel plasma concentration as a marker for platelet or endothelial activation could be demonstrated even weeks after moderate COVID-19, whereas, in vitro platelet function was comparable with non-infected controls. We conclude that COVID-19 and additional individual factors could lead to an increase of the sP-sel plasma level.

Dataset Information

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Publications

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

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