Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection
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Abstract
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SciScore for 10.1101/2020.12.18.20248336: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources The commercial laboratories antibody testing includes a limited set of high throughput antibody tests with validation against a known standard providing between 98% to 100% agreement with both known antibody-positive and antibody-negative specimens, with a 95% confidence interval of 99-100% agreement. antibody-negativesuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
SciScore for 10.1101/2020.12.18.20248336: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources The commercial laboratories antibody testing includes a limited set of high throughput antibody tests with validation against a known standard providing between 98% to 100% agreement with both known antibody-positive and antibody-negative specimens, with a 95% confidence interval of 99-100% agreement. antibody-negativesuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:While there are acknowledged limitations to RWD, it does provide a means to complement and supplement data from clinical trials in order to formulate hypotheses and provide information on patients or clinical scenario that are not well-represented in clinical trials.30–33 It is particularly well-suited to situations such as an emerging pandemic, where urgent questions require rapid, near real-time answers. To be clear, however, this RWD analysis has significant limitations compared to a classical prospective seroprotection trial. It is not known whether the rate of SARS-CoV-2 exposure or pattern of longitudinal follow-up was comparable between the two groups. It is also not known if the positive NAAT results in either group were associated with clinical signs of infection. Perhaps most importantly, it is not known how long any protective effect of serostatus may last beyond the studied 90 days. These questions remain to be addressed by further research. That research can also shed light on whether a seropositive individual who subsequently becomes seronegative may be associated with reduced protection and the degree to which protection associated with seropositivity may actually be mediated by antibodies versus other forms (e.g. T-cell based) immunity.6
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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Our take
In this study, available as a preprint and thus not yet been peer-reviewed, antibody positivity appeared to show short term protection against reinfection compared to those without antibodies to SARS-CoV-2, though it is not clear how long this protection could last as the study follow-up was limited to 7-8 months with a median follow-up of ~50 days. More research with well-defined cohorts over extended periods of time could help clarify the best correlates of protection and duration of protection.
Study design
retrospective-cohort
Study population and setting
There is currently limited data on whether development of IgG antibodies following infection from SARS-CoV-2 leads to protection against reinfection. The authors sought to determine whether being antibody positive for SARS-CoV-2 predicted …
Our take
In this study, available as a preprint and thus not yet been peer-reviewed, antibody positivity appeared to show short term protection against reinfection compared to those without antibodies to SARS-CoV-2, though it is not clear how long this protection could last as the study follow-up was limited to 7-8 months with a median follow-up of ~50 days. More research with well-defined cohorts over extended periods of time could help clarify the best correlates of protection and duration of protection.
Study design
retrospective-cohort
Study population and setting
There is currently limited data on whether development of IgG antibodies following infection from SARS-CoV-2 leads to protection against reinfection. The authors sought to determine whether being antibody positive for SARS-CoV-2 predicted risk of future infection compared to being antibody negative. The authors conducted a retrospective cohort study using a national sample in the US with commercial laboratory results linked to longitudinal claims data, electronic health records and billing data and medical records. Patients with at least one antibody test on or after January 2020 were classified by their antibody status on first index test, and then compared on their risk of having evidence of viral shedding using a nucleic acid amplification test (NAAT) through August 26, 2020. Subsequent antibody tests were also included in the study to examine loss of detectable SARS-CoV-2 antibodies over time.
Summary of main findings
The authors identified 3,257,478 patients with at least one index antibody test of whom 88.3% were negative and 11.6% were positive at baseline. Median follow-up was 47 days for the seronegative group and 54 days for the seropositive group. In total 18.4% of those who were seropositive at baseline converted to seronegative by the end of study. Among those positive at baseline, 11.0% (n=41,587) had a NAAT test during follow-up, while among those negative at baseline, 9.5% (n=273,735) did. The ratio of positive NAAT tests at follow-up over the first 0-30 days comparing those who had a positive antibody test at baseline to those who were antibody negative at baseline was 2.85 (95% CI: 2.73 - 2.97), likely reflecting shedding of viral particles from the initial infection. After 30 days, the ratio of NAAT positive tests was lower for those who were initially antibody positive compared to those initially antibody negative (ratio 0.67; 95% CI: 0.60-0.74 from 31-60 days, 0.29; 95% CI: 0.24-0.35 from 61-90 days and 0.10; 95% CI: 0.05-0.19 at >90 days) likely reflecting antibody protection against reinfection in the short term.
Study strengths
The study sample was very large giving reasonably precise estimates of the relationship between antibody positivity and infection and allowing for breaking the results up into time periods to distinguish between first infections and repeat infections. In addition, the cohort included participants from around the US allowing for broad generalizability of the result in terms of region.
Limitations
One limitation of this analysis is the potential for misclassification of the antibody and NAAT results and the use of any type of antibody to define antibody positivity, even though IgM antibodies, for example, would not be expected to provide protection over time. Both of these limitations could lead to an underestimate the protective effect of longer lasting antibodies. There is likely some measurement error in the NAAT test itself but there also limited ability to differentiate between new and persisting viral shedding, particularly early after the first antibody test. Finally, selection bias may have impacted the results given that it isn’t clear who would have had more than one antibody test or the reasons for testing – including, curiosity, symptoms, or work requirements - and how that relates to possible risk of exposure.
Value added
There is currently limited data on the duration of protection from antibodies following SARS-CoV-2 infection, and as such, this adds important information on short term risk of reinfection.
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SciScore for 10.1101/2020.12.18.20248336: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Patients were indexed as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test recorded in the database. antibody-negative according to their first SARS-CoV-2suggested: NoneAdditional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, such as recorded signs and symptoms or prior … SciScore for 10.1101/2020.12.18.20248336: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Patients were indexed as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test recorded in the database. antibody-negative according to their first SARS-CoV-2suggested: NoneAdditional 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. NAAT+suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
While there are acknowledged limitations to RWD, it does provide a means to complement and supplement data from clinical trials in order to formulate hypotheses and provide information on patients or clinical scenario that are not well-represented in clinical trials.30–33 It is particularly wellsuited to situations such as an emerging pandemic, where urgent questions require rapid, near real-time answers. To be clear, however, this RWD analysis has significant limitations compared to a classical prospective seroprotection trial. It is not known whether the rate of SARS-CoV-2 exposure or pattern of longitudinal follow-up was comparable between the two groups. It is also not known if the positive NAAT results in either group were associated with clinical signs of infection. Perhaps most importantly, it is not known how long any protective effect of serostatus may last beyond the studied 90 days. These questions remain to be addressed by further research. That research can also shed light on whether a seropositive individual who subsequently becomes seronegative may be associated with reduced protection and the degree to which protection associated with seropositivity may actually be mediated by antibodies versus other forms (e.g. T-cell based) immunity.6 Acknowledgements: This work was supported by the National Cancer Institute, Office of the Director. We would like to thank Dr. Tony Fauci and Dr. Cliff Lane for comments on the manuscript. Authors RAH, JAR, CAK, WT are employee...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
About SciScore
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