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

  • 3,260
    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
    Xiaoning Wang, Jinxiang Zhao ... Dong Liu
    Research Article

    Artificially sweetened beverages containing noncaloric monosaccharides were suggested as healthier alternatives to sugar-sweetened beverages. Nevertheless, the potential detrimental effects of these noncaloric monosaccharides on blood vessel function remain inadequately understood. We have established a zebrafish model that exhibits significant excessive angiogenesis induced by high glucose, resembling the hyperangiogenic characteristics observed in proliferative diabetic retinopathy (PDR). Utilizing this model, we observed that glucose and noncaloric monosaccharides could induce excessive formation of blood vessels, especially intersegmental vessels (ISVs). The excessively branched vessels were observed to be formed by ectopic activation of quiescent endothelial cells (ECs) into tip cells. Single-cell transcriptomic sequencing analysis of the ECs in the embryos exposed to high glucose revealed an augmented ratio of capillary ECs, proliferating ECs, and a series of upregulated proangiogenic genes. Further analysis and experiments validated that reduced foxo1a mediated the excessive angiogenesis induced by monosaccharides via upregulating the expression of marcksl1a. This study has provided new evidence showing the negative effects of noncaloric monosaccharides on the vascular system and the underlying mechanisms.

    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease
    Amanda C Perofsky, John Huddleston ... Cécile Viboud
    Research Article

    Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997—2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity.