Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modeling study

Abstract

We performed a systematic review and meta-analysis of SARS-CoV-2 serology studies to estimate time-dependent sensitivity for a large set of serological assays. We find that seroreversion depends strongly on the antigen and the analytic technique of the assay. We estimate the average time-varying sensitivity for different types of assays, as defined by their technical characteristics, which can be used to approximate the sensitivity of out-of-sample assays. We find large variability between types of assays, with assays of certain characteristics (nucleocapsid antigen, lateral flow assay) having an average of 20% sensitivity at 6 months, while others (receptor-binding domain antigen, sandwich design) have 98% sensitivity. Importantly, we estimate that almost a third of included assays depart significantly from manufacturer specified sensitivity after 6 months. Our analysis outlines the importance of monitoring the seroreversion of serological tests, and provides a tool for researchers to account for this phenomenon.

SARS-CoV-2 Antibody Prevalence among Industrial Livestock Operation Workers and Nearby Community Residents, North Carolina, 2021 to 2022

“…This waning, especially of N-specific antibodies, may have caused us to underestimate infection-induced SARS-CoV-2 exposure. Variability in commercial anti-N antibody assay performance suggests faster waning of N-specific antibodies may be related to assay characteristics rather than biological waning ( 46 – 48 ). We used a quantitative antibody assay, which generally perform better than lateral flow assays ( 48 ).…”

“…Variability in commercial anti-N antibody assay performance suggests faster waning of N-specific antibodies may be related to assay characteristics rather than biological waning ( 46 – 48 ). We used a quantitative antibody assay, which generally perform better than lateral flow assays ( 48 ). Assays targeting RBD generally have the slowest decay and loss of sensitivity over time, followed by S, followed by N; our multiplex approach incorporating both RBD and N may have allowed us to maintain sensitivity with a lower N cutoff ( 43 , 48 ).…”

“…We used a quantitative antibody assay, which generally perform better than lateral flow assays ( 48 ). Assays targeting RBD generally have the slowest decay and loss of sensitivity over time, followed by S, followed by N; our multiplex approach incorporating both RBD and N may have allowed us to maintain sensitivity with a lower N cutoff ( 43 , 48 ). Variability in anti-N antibody assay sensitivity over time is also a limitation when comparing our SARS-CoV-2 infection-induced antibody prevalence estimates to other studies.…”

“…Variability in anti-N antibody assay sensitivity over time is also a limitation when comparing our SARS-CoV-2 infection-induced antibody prevalence estimates to other studies. Neighbors et al used the Abbott Alinity N IgG assay to estimate seroprevalence in the C3PI Cabarrus County cohort, which Owusu-Boaitey found to be one of the poorer-performing assays ( 30 , 48 ). If the Abbott Alinity N IgG assay had a lower sensitivity over time compared to our assay, prevalence ratios comparing our ILO participants to the C3PI cohort could be overestimated.…”

Age-stratified infection fatality rate of COVID-19 in the non-elderly informed from pre-vaccination national seroprevalence studies

“…Antibody titers may decline over time. For example, a modelling study estimating the average time from seroconversion to seroreversion at 3-4 months (11) and other investigators have also found steep decreases in antibody assay sensitivity over time (12) and a systematic review found large variability in seroreversion rates across assays and studies (13). Therefore, for consistency, if there were multiple different time points when seroprevalence was assessed in a given study, we selected the one that gave the highest seroprevalence estimate and when there was a tie we chose the earliest one (in a sensitivity analysis, we excluded from the calculations studies where the chosen time point was not the latest).…”