1. Epidemiology and Global Health
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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
Research Article
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Cite this article as: eLife 2021;10:e69866 doi: 10.7554/eLife.69866

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.

Reviewing Editor

  1. Jameel Iqbal, James J Peters Veterans Affairs Medical Center, United States

Publication history

  1. Received: April 28, 2021
  2. Accepted: June 3, 2021
  3. Accepted Manuscript published: June 4, 2021 (version 1)

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.

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Further reading

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    In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺1-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺1-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺1-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.

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    Background:

    Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample.

    Methods:

    We assessed global effect sizes of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta, and liver of UK Biobank participants who reported drinking alcohol.

    Results:

    We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (–1.7 × 10−3 ± 0.76 × 10−3 per doubling of alcohol consumption, p=3.0 × 10−14). Alcohol consumption was also associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption.

    Conclusions:

    Our results imply that there is not a ‘safe threshold’ below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.

    Funding:

    See acknowledgements.