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Observational Study
. 2021 May 1;181(5):672-679.
doi: 10.1001/jamainternmed.2021.0366.

Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection

Raymond A Harvey  1 , Jeremy A Rassen  1 , Carly A Kabelac  1 , Wendy Turenne  1 , Sandy Leonard  2 , Reyna Klesh  2 , William A Meyer 3rd  3 , Harvey W Kaufman, Steve Anderson  4 , Oren Cohen  4 , Valentina I Petkov  5 , Kathy A Cronin  5 , Alison L Van Dyke  5 , Douglas R Lowy  5 , Norman E Sharpless  5 , Lynne T Penberthy  5
Affiliations
Observational Study

Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection

Raymond A Harvey et al. JAMA Intern Med. .

Abstract

Importance: 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.

Objective: 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.

Results: 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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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Diagram of Study Design
This figure shows the key elements of the study design. The study index date for each patient was the day of the patient’s first observed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody test on or after January 8, 2020. Follow-up occurred in 30-day increments after the index date. COVID-19 indicates coronavirus disease 2019; NAAT indicates nucleic acid amplification test.
Figure 2.
Figure 2.. Subsequent Diagnostic Nucleic Acid Amplification Test (NAAT) Results at 30-Day Intervals
This figure shows the results of diagnostic NAAT after initial antibody testing. A, The line shows the ratio of positive diagnostic tests among those who initially tested positive for antibodies vs those who initially tested negative. B, Over each time period, the dark blue bars show the percent of patients who tested positive for the diagnostic test among those who initially tested positive for antibodies with corresponding confidence intervals. The light blue bars show the percent of patients who tested positive for the diagnostic test among those who initially tested negative for antibodies with corresponding confidence intervals.
Figure 3.
Figure 3.. Subsequent Antibody Testing Among Index Antibody-Positive Patients Over Time
This figure shows the results of subsequent antibody tests among the group of patients with an initial positive antibody test (n = 378 606). A, The line shows the percentage of patients who subsequently tested negative in each time period. B, Over the 4 time periods, light blue bars represent those who subsequently tested negative for antibodies, while dark blue bars show those who subsequently tested positive.
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References

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