Seroprevalence of SARS-CoV-2 in Slovenia: results of two rounds of a nationwide population study on a probability-based sample, challenges and lessons learned

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Clin Microbiol Infect. 2021 Apr 7:S1198-743X(21)00144-0. doi: 10.1016/j.cmi.2021.03.009. Online ahead of print.


OBJECTIVES: Seroprevalence surveys provide crucial information on cumulative SARS-CoV-2 exposure. This Slovenian nationwide population study is the first longitudinal 6-month serosurvey using probability-based sample across all age categories.

METHODS: Each participant supplied two blood samples: 1,316 samples in April 2020 (first round) and 1,211 in October/November 2020 (second round). The first-round sera were tested using Euroimmun Anti-SARS-CoV-2 ELISA IgG (ELISA) and due to uncertain estimates 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.

RESULTS: The populations of both rounds matched the overall population (n=3,000), with minor settlement type and age differences. The first-round seroprevalence corrected for ELISA’s manufacturer’s specificity was 2.78% (95%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 November 11, 2020, was 4.06% (95%HDI, 2.97-5.16%) and on October 3, 2020, unadjusted upper limit was 4.29% (95%HDI, 3.18-5.47%).

CONCLUSIONS: SARS-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 conducting in low-prevalence settings or during epidemic exponential growth and the usefulness of a Bayesian approach for overcoming complex methodological challenges.

PMID:33838303 | DOI:10.1016/j.cmi.2021.03.009