Real-world data suggest antibody positivity to SARS-CoV-2 is associated with a decreased risk of future infection
Authors: Harvey Raymond A. , Rassen Jeremy A. , Kabelac Carly A. , Turenne Wendy , Leonard Sandy , Klesh Reyna , Meyer William A. , Kaufman Harvey W. , Anderson Steve , Cohen Oren , Petkov Valentina I. , Cronin Kathy A. , Van Dyke Alison L. , Lowy Douglas R. , Sharpless Norman E. , Penberthy Lynne T. 
Published: December 2020

Importance

There is limited evidence regarding whether the presence of serum antibodies to SARS-CoV-2 is associated with a decreased risk of future infection. Understanding susceptibility to infection and the role of immune memory is important for identifying at-risk populations and could have implications for vaccine deployment.

Objective

The purpose of this study was to evaluate subsequent evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among individuals who are antibody-positive compared with those who are antibody-negative, using real-world data.

Design

This was an observational descriptive cohort study.

Participants

The study utilized a national sample to create cohorts from a de-identified dataset composed of commercial laboratory test results, open and closed medical and pharmacy claims, electronic health records, hospital billing (chargemaster) data, and payer enrollment files from the United States. Patients were indexed as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test recorded in the database. Patients with more than 1 antibody test on the index date where results were discordant were excluded.

Main Outcomes/Measures

Primary endpoints were index antibody test results and post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, as 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, such as recorded signs and symptoms or prior evidence of COVID-19 (diagnoses or NAAT+) and recorded comorbidities.

Results

We included 3,257,478 unique patients with an index antibody test. Of these, 2,876,773 (88.3%) had a negative index antibody result, 378,606 (11.6%) had a positive index antibody result, and 2,099 (0.1%) had an inconclusive index antibody result. Patients with a negative antibody test were somewhat older at index than those with a positive result (mean of 48 versus 44 years). A fraction (18.4%) of individuals who were initially seropositive converted to seronegative over the follow up period. During the follow-up periods, the ratio (CI) of positive NAAT results among individuals who had a positive antibody test at index versus those with a negative antibody test at index was 2.85 (2.73 - 2.97) at 0-30 days, 0.67 (0.6 - 0.74) at 31-60 days, 0.29 (0.24 - 0.35) at 61-90 days), and 0.10 (0.05 - 0.19) at >90 days.

Conclusions

Patients who display positive antibody tests are initially more likely to have a positive NAAT, consistent with prolonged RNA shedding, but over time become markedly less likely to have a positive NAAT. This result suggests seropositivity using commercially available assays is associated with protection from infection. The duration of protection is unknown and may wane over time; this parameter will need to be addressed in a study with extended duration of follow up.

Key Points

Question

Can real-world data be used to evaluate the comparative risk of SARS-CoV-2 infection for individuals who are antibody-positive versus antibody-negative?

Finding

Of patients indexed on a positive antibody test, 10 of 3,226 with a NAAT (0.3%) had evidence of a positive NAAT > 90 days after index, compared with 491 of 16,157 (3.0%) indexed on a negative antibody test.

Meaning

Individuals who are seropositive for SARS-CoV-2 based on commercial assays may be at decreased future risk of SARS-CoV-2 infection.