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Agreement between self-reported COVID-19 and dried blood spot serology

Sheppard, N.; Carroll, M. T. C.; Borg, B. M.; Toh, Z. Q.; Licciardi, P.; Smith, C. L.; Ikin, J. F.; Abramson, M. J.; Walker-Bone, K.; Lane, T. J.

2025-04-10 epidemiology
10.1101/2025.04.08.25325501 medRxiv
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IntroductionIdentifying likely COVID-19 cases with good accuracy is essential for epidemiological research on the pandemics health effects. Therefore, evaluating case detection methods for cost-effectiveness and reliability is important. We investigated the agreement between a validated self-report questionnaire for COVID-19 and dried blood spot serology for SARS-CoV-2 antibodies. MethodsBetween June and October 2023, 311 adults completed the self-report COVID-19 questionnaire validated by the Avon Longitudinal Study of Parents and Children, and provided fingertip blood samples which underwent Enzyme Linked Immunosorbent Assay to quantify IgG antibodies to SARS-CoV-2 nucleocapsid (N)-protein. We applied several statistical approaches to assess agreement: Cohens Kappa measure of inter-rater reliability; positive (PPV) and negative (NPV) predictive values; logistic regressions of the year of most recent self-reported COVID-19 on serostatus; and linear regressions of N-protein antibody concentrations. ResultsTwo-thirds (203, 65%) of participants self-reported a history of COVID-19 whereas one-third (98, 32%) were seropositive for SARS-CoV-2 N-protein antibodies. Across all years, there was only "fair" agreement ({kappa} = 0.23 [95%CI 0.15 - 0.31]). Self-reported COVID-19 had a PPV of 41% and an NPV of 87% for SARS-CoV-2 seropositivity. PPV was low for 2020-21 (36%) and 2022 (33%), but higher (75%) for participants whose most recent case was in 2023. Compared to participants with no self-reported history of COVID-19, those reporting SARS-CoV-2 infection in 2023 had 23 times greater odds of being seropositive (95%CI: 9.18-62.5), and had 1,079% (617-1,838%) higher N-protein concentrations, after adjustment for confounders. ConclusionA validated COVID-19 self-report questionnaire is useful for identifying people who have previously had COVID-19 and may be reasonably accurate in identifying when an infection occurred, at least within a calendar year. Furthermore, consistent with existing evidence, serological testing becomes much less sensitive over time.

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