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Clinical MedicineIn-Press PreviewInfectious diseaseVirology Free access | 10.1172/JCI144930

Clinical, laboratory, and temporal predictors of neutralizing antibodies to SARS-CoV-2 among COVID-19 convalescent plasma donor candidates

Jim Boonyaratanakornkit,1 Chihiro Morishima,2 Stacy Selke,2 Danniel Zamora,1 Sarah A. McGuffin,3 Adrienne E. Shapiro,4 Victoria L. Campbell,3 Christopher L. McClurkan,3 Lichen Jing,3 Robin Gross,5 Janie Liang,5 Elena Postnikova,5 Steven Mazur,5 Vladimir V. Lukin,6 Anu Chaudhary,2 Marie K. Das,2 Susan L. Fink,2 Andrew Bryan,2 Alexander L. Greninger,2 Keith R. Jerome,2 Michael R. Holbrook,5 Terry B. Gernsheimer,3 Mark H. Wener,2 Anna Wald,3 and David M. Koelle3

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

Find articles by Selke, S. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

Find articles by Zamora, D. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

Find articles by Das, M. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

Find articles by Bryan, A. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

Find articles by Jerome, K. in: JCI | PubMed | Google Scholar |

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

Find articles by Wener, M. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

Find articles by Wald, A. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

3Department of Medicine, University of Washington, Seattle, United States of America

4Department of Global Health, University of Washington, Seattle, United States of America

5Division of Clinical Research, National Institutes of Health, Frederick, United States of America

6PCE Labs, Kearney, Chicago, United States of America

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Published December 15, 2020 - More info

J Clin Invest. https://doi.org/10.1172/JCI144930.
Copyright © 2020, American Society for Clinical Investigation
Published December 15, 2020 - Version history
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Abstract

Background: SARS-CoV-2-specific antibodies may protect from reinfection and disease, providing rationale for administration of plasma containing SARS-CoV-2 neutralizing antibodies (nAb) as a treatment for COVID-19. Clinical factors and laboratory assays to streamline plasma donor selection, and the durability of nAb responses, are incompletely understood.

Methods: Potential convalescent plasma donors with virologically-documented SARS-CoV-2 infection were tested for serum IgG to SARS-CoV-2 spike protein S1 domain, nucleoprotein (NP), and for nAb.

Results: Amongst 250 consecutive persons, including 27 (11%) requiring hospitalization, studied a median of 67 days since symptom onset, 97% were seropositive on one or more assays. Sixty percent of donors had nAb titers ≥1:80. Correlates of higher nAb titer included older age (adjusted odds ratio [AOR] 1.03/year of age, 95% CI 1.00-1.06), male sex (AOR 2.08, 95% CI 1.13-3.82), fever during acute illness (AOR 2.73, 95% CI 1.25-5.97), and disease severity represented by hospitalization (AOR 6.59, 95% CI 1.32-32.96). Receiver operating characteristic (ROC) analyses of anti-S1 and anti-NP antibody results yielded cutoffs that corresponded well with nAb titers, with the anti-S1 assay being slightly more predictive. NAb titers declined in 37 of 41 paired specimens collected a median of 98 days (range, 77-120) apart (P<0.001). Seven individuals (2.8%) were persistently seronegative and lacked T cell responses.

Conclusions: Nab titers correlated with COVID-19 severity, age, and sex. Standard commercially available SARS-CoV-2 IgG results can serve as useful surrogates for nAb testing. Functional nAb levels were found to decline and a small proportion of persons recovered from COVID-19 lack adaptive immune responses.

Graphical Abstract
graphical abstract
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  • Version 1 (December 15, 2020): In-Press Preview
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