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dc.contributor.authorTorres Ortiz, Arturo
dc.contributor.authorFenn Torrente, Fernanda
dc.contributor.authorTwigg, Adam
dc.contributor.authorHatcher, James
dc.contributor.authorSaso, Anja
dc.contributor.authorLam, Tanya
dc.contributor.authorJohnson, Marina
dc.contributor.authorWagstaffe, Helen
dc.contributor.authorDhillon, Rishi
dc.contributor.authorMai, Anabelle Lea
dc.contributor.authorGoldblatt, David
dc.contributor.authorStill, Rachel
dc.contributor.authorBuckland, Matthew
dc.contributor.authorGilmour, Kimberly
dc.contributor.authorGrandjean, Louis
dc.date.accessioned2022-06-29T19:44:19Z
dc.date.available2022-06-29T19:44:19Z
dc.date.issued2022-06-22
dc.date.submitted2022-01-22
dc.identifier.issn2045-2322
dc.identifier.others41598-022-14351-2
dc.identifier.other14351
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338476
dc.description.abstractSensitive 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.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/250/255
dc.subject/631/250/255/2514
dc.subjectarticle
dc.titleThe influence of time on the sensitivity of SARS-CoV-2 serological testing.
dc.typeArticle
dc.date.updated2022-06-29T19:44:19Z
prism.issueIdentifier1
prism.publicationNameSci Rep
prism.volume12
dc.identifier.doi10.17863/CAM.85889
dcterms.dateAccepted2022-06-06
rioxxterms.versionofrecord10.1038/s41598-022-14351-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn2045-2322
pubs.funder-project-idWellcome Trust (220565/Z/20/Z, 201470/Z/16/Z)
pubs.funder-project-idGreat Ormond Street Hospital Charity (VC0921)
cam.issuedOnline2022-06-22


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