The influence of time on the sensitivity of SARS-CoV-2 serological testing.
Torres Ortiz, Arturo
Fenn Torrente, Fernanda
Mai, Anabelle Lea
Springer Science and Business Media LLC
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Torres Ortiz, A., Fenn Torrente, F., Twigg, A., Hatcher, J., Saso, A., Lam, T., Johnson, M., et al. (2022). The influence of time on the sensitivity of SARS-CoV-2 serological testing.. Sci Rep, 12 (1) https://doi.org/10.1038/s41598-022-14351-2
Sensitive serological testing is essential to estimate the proportion of the population exposed or infected with SARS-CoV-2, to guide booster vaccination and to select patients for treatment with anti-SARS-CoV-2 antibodies. The performance of serological tests is usually evaluated at 14-21 days post infection. This approach fails to take account of the important effect of time on test performance after infection or exposure has occurred. We performed parallel serological testing using 4 widely used assays (a multiplexed SARS-CoV-2 Nucleoprotein (N), Spike (S) and Receptor Binding Domain assay from Meso Scale Discovery (MSD), the Roche Elecsys-Nucleoprotein (Roche-N) and Spike (Roche-S) assays and the Abbott Nucleoprotein assay (Abbott-N) on serial positive monthly samples collected as part of the Co-STARs study ( www.clinicaltrials.gov , NCT04380896) up to 200 days following infection. Our findings demonstrate the considerable effect of time since symptom onset on the diagnostic sensitivity of different assays. Using a time-to-event analysis, we demonstrated that 50% of the Abbott nucleoprotein assays will give a negative result after 175 days (median survival time 95% CI 168-185 days), compared to the better performance over time of the Roche Elecsys nucleoprotein assay (93% survival probability at 200 days, 95% CI 88-97%). Assays targeting the spike protein showed a lower decline over the follow-up period, both for the MSD spike assay (97% survival probability at 200 days, 95% CI 95-99%) and the Roche Elecsys spike assay (95% survival probability at 200 days, 95% CI 93-97%). The best performing quantitative Roche Elecsys Spike assay showed no evidence of waning Spike antibody titers over the 200-day time course of the study. We have shown that compared to other assays evaluated, the Abbott-N assay fails to detect SARS-CoV-2 antibodies as time passes since infection. In contrast the Roche Elecsys Spike Assay and the MSD assay maintained a high sensitivity for the 200-day duration of the study. These limitations of the Abbott assay should be considered when quantifying the immune correlates of protection or the need for SARS-CoV-2 antibody therapy. The high levels of maintained detectable neutralizing spike antibody titers identified by the quantitative Roche Elecsys assay is encouraging and provides further evidence in support of long-lasting SARS-CoV-2 protection following natural infection.
Article, /631/250/255, /631/250/255/2514, article
Wellcome Trust (220565/Z/20/Z, 201470/Z/16/Z)
Great Ormond Street Hospital Charity (VC0921)
External DOI: https://doi.org/10.1038/s41598-022-14351-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338476