Abstract
ObjectivesSeroprevalence surveys provide crucial information on cumulative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. This Slovenian nationwide population study is the first longitudinal 6-month serosurvey using probability-based samples across all age categories. MethodsEach participant supplied two blood samples: 1316 samples in April 2020 (first round) and 1211 in October/November 2020 (second round). The first-round sera were tested using Euroimmun Anti-SARS-CoV-2 ELISA IgG (ELISA) and, because of uncertain estimates, were retested using Elecsys Anti-SARS-CoV-2 (Elecsys-N) and Elecsys Anti-SARS-CoV-2 S (Elecsys-S). The second-round sera were concomitantly tested using Elecsys-N/Elecsys-S. ResultsThe populations of both rounds matched the overall population (n = 3000), with minor settlement type and age differences. The first-round seroprevalence corrected for the ELISA manufacturer's specificity was 2.78% (95% highest density interval [HDI] 1.81%–3.80%), corrected using pooled ELISA specificity calculated from published data 0.93% (95% CI 0.00%–2.65%), and based on Elecsys-N/Elecsys-S results 0.87% (95% HDI 0.40%–1.38%). The second-round unadjusted lower limit of seroprevalence on 11 November 2020 was 4.06% (95% HDI 2.97%–5.16%) and on 3 October 2020, unadjusted upper limit was 4.29% (95% HDI 3.18%–5.47%). ConclusionsSARS-CoV-2 seroprevalence in Slovenia increased four-fold from late April to October/November 2020, mainly due to a devastating second wave. Significant logistic/methodological challenges accompanied both rounds. The main lessons learned were a need for caution when relying on manufacturer-generated assay evaluation data, the importance of multiple manufacturer-independent assay performance assessments, the need for concomitant use of highly-specific serological assays targeting different SARS-CoV-2 proteins in serosurveys conducted in low-prevalence settings or during epidemic exponential growth and the usefulness of a Bayesian approach for overcoming complex methodological challenges.
Highlights
The coronavirus disease 2019 (COVID-19) pandemic has already affected over 120 million people, with over 2.6 million COVID-19related deaths as of 16 March 2021
Uncorrected crude seroprevalence based on enzyme-linked immunosorbent assay (ELISA) results was estimated at 3.11%, seroprevalence corrected for the manufacturer's estimate of ELISA specificity at 2.78% (95% high-density interval (HDI) 1.81%e3.80%) and seroprevalence corrected for the estimate of ELISA specificity based on our meta-analysis at 0.93%
Seroprevalence surveys on a probability-based sample provide crucial information on cumulative SARS-CoV-2 exposure in communities. Such serosurveys are useful in settings where limited SARS-CoV-2 RNA testing and/or contact tracing capacity prevents reliable assessment of the COVID-19 burden through cumulative incidence data from official notification systems, which is an unfortunate reality in most of the world
Summary
The coronavirus disease 2019 (COVID-19) pandemic has already affected over 120 million people, with over 2.6 million COVID-19related deaths as of 16 March 2021. Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal swabs is a COVID-19 reference diagnostic standard [1,2]. Because of a significant number of asymptomatic/mild infections, demanding implementation and scale-up of molecular testing and frequent changes in testing strategies, the SARS-CoV-2 RNA positives identified represent only the tip of the pandemic iceberg [2e4]. Seroprevalence surveys measuring the population immune response to SARS-CoV-2 remain integral for understanding cumulative population exposure and insight into pandemic dynamics during the COVID-19 pre-vaccination era [4,5]. The most recent systematic review and meta-analysis, assessing non-peer-reviewed seroprevalence surveys deposited in open-access preprint repositories or posted at websites, showed a general lack of peer-reviewed population-based studies from much of the world and significant data heterogeneity, and called for longitudinal surveys to continually monitor seroprevalence around the globe [2]
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