4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25113-5

Keywords

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Funding

  1. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, and Biomedical Advanced Research and Development Authority [75A50120C00096]
  2. National Center for Advancing Translational Sciences (NCATS) [UL1TR002377]
  3. National Heart, Lung, and Blood Institute (NHLBI) [5R35HL139854, 1F32HL154320]
  4. Natural Sciences and Engineering Research Council of Canada (NSERC) [PDF-532926-2019]
  5. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [5T32DK07352]
  6. National Institute of Allergy and Infectious Disease (NIAID) [R21 AI145356, R21 AI152318, R21 AI154927, R01 AI152078 9]
  7. National Heart Lung and Blood Institute [RO1 HL059842]
  8. National Institute on Aging (NIA) [U54AG044170]
  9. Schwab Charitable Fund
  10. United Health Group
  11. National Basketball Association (NBA)
  12. Millennium Pharmaceuticals
  13. Octapharma USA, Inc.
  14. Mayo Clinic

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Successful COVID-19 therapeutics and vaccines have utilized the immune response to the virus, but locally-evolving variants may impact treatment effectiveness. Near-sourced convalescent plasma has higher efficacy in causing death within 30 days of transfusion.
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. Regional differences in SARS-CoV-2 variants may affect treatment outcome. Here, the authors show that near-sourced convalescent plasma has higher efficacy, as defined by death within 30 days of transfusion, than plasma sourced more than 150 miles away.

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