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Can observational clinical data from commercial laboratories be used to evaluate the comparative risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for individuals who are antibody positive vs those who are antibody negative?
In this cohort study of more than 3.2 million US patients with a SARS-CoV-2 antibody test, 0.3% of those indexed with positive test results had evidence of a positive nucleic acid amplification test beyond 90 days after index, compared with 3.0% indexed with negative antibody test results.
Individuals who are seropositive for SARS-CoV-2 based on commercial assays may be at decreased future risk of SARS-CoV-2 infection.
Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment.
The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data.
Design, Setting, and Participants
The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database.
Main Outcomes and Measures
Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities.
The cohort included 3 257 478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2 876 773 (88.3%) had a negative index antibody result, and 378 606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days.
Conclusions and Relevance
In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: January 28, 2021.
Published Online: February 24, 2021. doi:10.1001/jamainternmed.2021.0366
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Harvey RA et al. JAMA Internal Medicine.
Corresponding Author: Lynne T. Penberthy, MD, MPH, National Cancer Institute, National Institutes of Health, 9609 Medical Center Dr, Rockville, MD 20850 (firstname.lastname@example.org).
Author Contributions: Mr Harvey and Dr Rassen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Harvey, Rassen, Turenne, Leonard, Klesh, Kaufman, Cohen, Petkov, Cronin, Van Dyke, Lowy, Sharpless, Penberthy.
Acquisition, analysis, or interpretation of data: Harvey, Rassen, Kabelac, Turenne, Leonard, Klesh, Meyer, Kaufman, Anderson, Cohen, Petkov, Lowy, Sharpless, Penberthy.
Drafting of the manuscript: Harvey, Rassen, Kabelac, Kaufman, Anderson, Sharpless, Penberthy.
Critical revision of the manuscript for important intellectual content: Harvey, Rassen, Turenne, Leonard, Klesh, Meyer, Kaufman, Anderson, Cohen, Petkov, Cronin, Van Dyke, Lowy, Sharpless, Penberthy.
Statistical analysis: Harvey, Rassen, Kabelac, Turenne.
Obtained funding: Harvey, Leonard, Klesh, Cohen.
Administrative, technical, or material support: Harvey, Rassen, Kabelac, Turenne, Leonard, Klesh, Meyer, Kaufman, Cohen, Petkov, Sharpless.
Supervision: Harvey, Rassen, Turenne, Leonard, Klesh, Petkov, Cronin, Van Dyke, Sharpless, Penberthy.
Other - engagement of laboratory collaboration partners: Leonard, Klesh.
Conflict of Interest Disclosures: Mr Harvey is an employee of Aetion, Inc, which received payment for services for the submitted work. Dr Rassen reported other from the National Institutes of Health during the conduct of the study, and is an employee of and has an ownership stake in Aetion, Inc. Ms Kabelac is an employee of Aetion, which received payment for services for the submitted work during the conduct of the study. Ms Turenne is an employee of Aetion, which received payment for services for the submitted work. Ms Leonard reported other from the National Cancer Institute, payment made to HealthVerity for data license and analytics during the conduct of the study; request for proposal from National Cancer Institute; and nonfinancial support from the US Food and Drug Administration outside the submitted work. Ms Klesh reported other from the National Cancer Institute, payment made to HealthVerity for data license and analytics during the conduct of the study; request for proposal from National Cancer Institute and nonfinancial support from the US Food and Drug Administration outside the submitted work. Dr Kaufman is an employee of and owns stock in Quest Diagnostics. Dr Anderson was senior vice president of LabCorp during the conduct of the study, and is on advisory boards for OmniSeq, GeneCentric, Emulate, Kiatech, and Johnson & Johnson. Dr Cohen is an employee and shareholder of Covance (LabCorp) during the conduct of the study. No other disclosures were reported.
Funding/Support: This work was funded by the National Cancer Institute, Office of the Director.
Role of the Funder/Sponsor: The National Cancer Institute had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We would like to thank Tony Fauci, MD, and Cliff Lane, MD, for comments on the manuscript; both are associated with the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and neither received any compensation for their assistance with this article.
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