Real-world data suggest antibody positivity to SARS-CoV-2 is associated with a decreased risk of future infection

Abstract

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.

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 SARS-CoV-2 antibody test on or after January 8, 2020. Follow-up occurred in 30-day increments after the index date.

Figure 2.. Subsequent antibody testing among index antibody positive patients over time (n = 378,606)

This figure shows the results of subsequent antibody tests among the group of patients with an initial positive antibody test. Over the four time periods, blue bars represent those who subsequently test negative for antibodies, while red bars show those who subsequently test positive. The blue line shows the percentage of patients who subsequently tested negative in each time period.

Figure 3.. Subsequent Diagnostic (NAAT) Test Results at 30 Day Intervals

This figure shows the results of diagnostic (NAAT) testing after initial antibody testing. Over each time period, the red bars show those who test positive for the diagnostic test among those who initially tested positive for antibodies. The blue bars show those who test positive for the diagnostic test among those who initially tested negative for antibodies. The black line shows the ratio of positive diagnostic tests among those who initially tested positive for antibodies versus those who initially tested negative.