The Duration, Dynamics, and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Responses in Individual Healthcare Workers
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Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary.
Methods
We present 6 months of data from a longitudinal seroprevalence study of 3276 UK healthcare workers (HCWs). Serial measurements of SARS-CoV-2 anti-nucleocapsid and anti-spike IgG were obtained. Interval censored survival analysis was used to investigate the duration of detectable responses. Additionally, Bayesian mixed linear models were used to investigate anti-nucleocapsid waning.
Results
Anti-spike IgG levels remained stably detected after a positive result, for example, in 94% (95% credibility interval [CrI] 91–96%) of HCWs at 180 days. Anti-nucleocapsid IgG levels rose to a peak at 24 (95% CrI 19–31) days post first polymerase chain reaction (PCR)-positive test, before beginning to fall. Considering 452 anti-nucleocapsid seropositive HCWs over a median of 121 days from their maximum positive IgG titer, the mean estimated antibody half-life was 85 (95% CrI 81–90) days. Higher maximum observed anti-nucleocapsid titers were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity, and prior self-reported symptoms were independently associated with higher maximum anti-nucleocapsid levels and increasing age and a positive PCR test undertaken for symptoms with longer anti-nucleocapsid half-lives.
Conclusions
SARS-CoV-2 anti-nucleocapsid antibodies wane within months and fall faster in younger adults and those without symptoms. However, anti-spike IgG remains stably detected. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.
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SciScore for 10.1101/2020.11.02.20224824: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics: Deidentified data from staff testing were obtained from the Infections in Oxfordshire Research Database (IORD) which has generic Research Ethics Committee, Health Research Authority and Confidentiality Advisory Group approvals (19/SC/0403, 19/CAG/0144). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Statistical methods: Individuals with ≥1 positive antibody result (titre ≥1.40) and ≥2 antibody results were classified as showing rising titres only, falling or stable titres only, or both. ≥2suggested: NoneSoftware and Algorithms Sentences Res… SciScore for 10.1101/2020.11.02.20224824: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics: Deidentified data from staff testing were obtained from the Infections in Oxfordshire Research Database (IORD) which has generic Research Ethics Committee, Health Research Authority and Confidentiality Advisory Group approvals (19/SC/0403, 19/CAG/0144). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Statistical methods: Individuals with ≥1 positive antibody result (titre ≥1.40) and ≥2 antibody results were classified as showing rising titres only, falling or stable titres only, or both. ≥2suggested: NoneSoftware and Algorithms Sentences Resources Laboratory assays: Serology for SARS-CoV-2 IgG to nucleocapsid protein was performed using the Abbott Architect i2000 chemiluminescent microparticle immunoassay (CMIA; Abbott, Maidenhead, UK). Abbott Architectsuggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)Antibody levels ≥1.40 manufacturer’s arbitrary units were considered positive, 0.50-1.39 equivocal (following Abbott Diagnostics Product Information Letter PI1060-2020) and <0.5 negative. Abbottsuggested: (Abbott, RRID:SCR_010477)Results 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:Limitations: One limitation of our study was that our cohort of individuals consisted of adults of working age (17-69 years); further longitudinal studies will be required to investigate antibody trajectories in younger and older age groups. In addition, the small numbers of self-reported Black (n=25) and Other (n=36) ethnicities reduced/limited power to detect an association between these ethnicities and antibody trajectories. Furthermore, we do not account for multiple mediators, e.g. socioeconomic inequalities, that may link ethnicity to antibody responses in the absence of a direct causal relationship. Due to many of our staff developing symptoms before widespread SARS-CoV-2 PCR testing was available, only 34% of the antibody positive cohort had a documented positive PCR, and as a proportion of the cohort were asymptomatic throughout, we modelled time from maximum positive antibody test rather than time from first positive PCR or time from symptom onset in our main analysis of antibody durability. However under an exponential assumption, half-lives can be unbiasedly estimated from any measurements taken after a maximum; we excluded individuals with only evidence of rising titres to avoid underestimating half-lives. Further, data from those that were PCR positive were consistent with this analysis (Figure 6). Multiple different assays are in use globally to characterize antibody responses to SARS-CoV-2. Here we use a commercially-available anti-nucleocapsid IgG assay; howe...
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.
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- No protocol registration statement was detected.
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