Ultra-sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease

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Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential to identify active infection and monitor disease progression.

Methods

We used Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of coronavirus disease (COVID-19) patients. We studied plasma from 64 COVID-19 positive patients, 17 COVID-19 negative patients, and 34 pre-pandemic patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we quantified changes in 31 SARS-CoV-2 biomarkers in 272 longitudinal plasma samples obtained for 39 COVID-19 patients. Data were analyzed by hierarchical clustering and were compared to longitudinal RT-PCR test results and clinical outcomes.

Results

SARS-CoV-2 S1 and N antigens were detectable in 41 out of 64 COVID-19 positive patients. In these patients, full antigen clearance in plasma was observed a mean ± 95%CI of 5 ± 1 days after seroconversion and nasopharyngeal RT-PCR tests reported positive results for 15 ± 5 days after viral antigen clearance. Correlation between patients with high concentrations of S1 antigen and ICU admission (77%) and time to intubation (within one day) was statistically significant.

Conclusions

The reported SARS-CoV-2 Simoa antigen assay is the first to detect viral antigens in the plasma of COVID-19 positive patients to date. These data show that SARS-CoV-2 viral antigens in the blood are associated with disease progression, such as respiratory failure, in COVID-19 cases with severe disease.

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Author and article information

Contributors

David R Walt

Journal

Journal ID (nlm-ta): Clin Chem

Journal ID (iso-abbrev): Clin. Chem

Journal ID (publisher-id): clinchem

Title: Clinical Chemistry

Publisher: Oxford University Press

ISSN (Print): 0009-9147

ISSN (Electronic): 1530-8561

Publication date (Electronic): 08 September 2020

Electronic Location Identifier: hvaa213

Affiliations

[h1 ]Department of Pathology, Brigham and Women’s Hospital , Boston, MA, USA

[h2 ] Wyss Institute for Biologically Inspired Engineering, Harvard University , Boston, MA, USA

[h3 ] Harvard Medical School , Boston, MA, USA

[h4 ] Tufts University School of Medicine , Boston, MA, USA

[h5 ]Department of Cancer Immunology and Virology Dana-Farber Cancer Institute , Boston, MA, USA

[h6 ]Division of Infectious Diseases, Massachusetts General Hospital , Boston, MA, USA

[h7 ]Department of Medicine, Harvard Medical School , Boston, MA, USA

[h8 ]Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health , Boston MA, USA

Author notes

Alana F. Ogata, Adam M. Maley. These authors contributed equally

Correspondence to: 60 Fenwood Rd, Boston, 02116. 857-307-1112. dwalt@ 123456bwh.harvard.edu

Article

Publisher ID: hvaa213

DOI: 10.1093/clinchem/hvaa213

PMC ID: 7499543

SO-VID: e5984487-b624-45c2-a508-8c5b2e8d46b8

License:

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

History

Date received : 16 August 2020

Date revision received : 31 August 2020

Date accepted : 01 September 2020

Page count

Pages: 25

Custom metadata

edited-state accepted-manuscript

article-lifecycle PAP

Keywords: sars-cov-2,viral antigen,serological,longitudinal plasma samples,single molecule arrays

Data availability:

Keywords: sars-cov-2, viral antigen, serological, longitudinal plasma samples, single molecule arrays

Ultra-sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease

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