Convalescent plasma use in the United States was inversely correlated with COVID-19 mortality

  1. Arturo Casadevall  Is a corresponding author
  2. Quigly Dragotakes
  3. Patrick W Johnson
  4. Jonathon W Senefeld
  5. Stephen A Klassen
  6. R Scott Wright
  7. Michael J Joyner
  8. Nigel Paneth
  9. Rickey E Carter
  1. Johns Hopkins Bloomberg School of Public Health, United States
  2. Johns Hopkins School of Public Health, United States
  3. Mayo Clinic, United States
  4. Michigan State University, United States

Abstract

Background. The US Food and Drug Administration authorized Convalescent Plasma (CCP) therapy for hospitalized COVID-19 patients via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to use in about 500,000 patients during the first year of the pandemic for the US.

Methods. We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data.

Results. CCP usage per admission peaked in Fall 2020, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, CCP usage per admission declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (r = -0.52, P = 0.002) between CCP usage per hospital admission and deaths occurring two weeks after admission, and this finding was robust to examination of deaths taking place one, two or three weeks after admission. Changes in the number of hospital admissions, SARS-CoV-2 variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021.

Conclusions. A strong inverse correlation between CCP use and mortality per admission in the USA provides population level evidence consistent with the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths.

Funding. There was no specific funding for this study. AC was supported in part by RO1 HL059842 and R01 AI1520789; MJJ was supported in part by 5R35HL139854. This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority under Contract No. 75A50120C00096.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Arturo Casadevall

    Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States
    For correspondence
    acasade1@jhu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9402-9167
  2. Quigly Dragotakes

    Johns Hopkins School of Public Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Patrick W Johnson

    Mayo Clinic, Jacksonviille, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathon W Senefeld

    Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Stephen A Klassen

    Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. R Scott Wright

    Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael J Joyner

    Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Nigel Paneth

    Michigan State University, East Lansing, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Rickey E Carter

    Mayo Clinic, Jacksonville, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institute of Allergy and Infectious Diseases (AI1520789)

  • Arturo Casadevall

Biomedical Advanced Research and Development Authority (75A50120C00096)

  • Michael J Joyner

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2021, Casadevall et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,267
    views
  • 315
    downloads
  • 45
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Arturo Casadevall
  2. Quigly Dragotakes
  3. Patrick W Johnson
  4. Jonathon W Senefeld
  5. Stephen A Klassen
  6. R Scott Wright
  7. Michael J Joyner
  8. Nigel Paneth
  9. Rickey E Carter
(2021)
Convalescent plasma use in the United States was inversely correlated with COVID-19 mortality
eLife 10:e69866.
https://doi.org/10.7554/eLife.69866

Share this article

https://doi.org/10.7554/eLife.69866

Further reading

    1. Epidemiology and Global Health
    Marina Padilha, Victor Nahuel Keller ... Gilberto Kac
    Research Article Updated

    Background:

    The role of circulating metabolites on child development is understudied. We investigated associations between children’s serum metabolome and early childhood development (ECD).

    Methods:

    Untargeted metabolomics was performed on serum samples of 5004 children aged 6–59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children’s milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥1. The interaction between significant metabolites and the child’s age was tested.

    Results:

    Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child’s nutritional status, diet quality, and infant age. Cresol sulfate (β=–0.07; adjusted-p <0.001), hippuric acid (β=–0.06; adjusted-p <0.001), phenylacetylglutamine (β=–0.06; adjusted-p <0.001), and trimethylamine-N-oxide (β=–0.05; adjusted-p=0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged –1 SD: β=–0.05; pP=0.01;+1 SD: β=0.05; p=0.02) and methylhistidine (–1 SD: β = - 0.04; p=0.04;+1 SD: β=0.04; p=0.03).

    Conclusions:

    Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.

    Funding:

    Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.

    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease
    Gillian AM Tarr, Linda Chui ... Tim A McAllister
    Research Article

    Several areas of the world suffer a notably high incidence of Shiga toxin-producing Escherichia coli. To assess the impact of persistent cross-species transmission systems on the epidemiology of E. coli O157:H7 in Alberta, Canada, we sequenced and assembled E. coli O157:H7 isolates originating from collocated cattle and human populations, 2007–2015. We constructed a timed phylogeny using BEAST2 using a structured coalescent model. We then extended the tree with human isolates through 2019 to assess the long-term disease impact of locally persistent lineages. During 2007–2015, we estimated that 88.5% of human lineages arose from cattle lineages. We identified 11 persistent lineages local to Alberta, which were associated with 38.0% (95% CI 29.3%, 47.3%) of human isolates. During the later period, six locally persistent lineages continued to be associated with human illness, including 74.7% (95% CI 68.3%, 80.3%) of reported cases in 2018 and 2019. Our study identified multiple locally evolving lineages transmitted between cattle and humans persistently associated with E. coli O157:H7 illnesses for up to 13 y. Locally persistent lineages may be a principal cause of the high incidence of E. coli O157:H7 in locations such as Alberta and provide opportunities for focused control efforts.