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We have read with a great interest the article written by Song and colleagues1 assessing seroprevalence of coronavirus disease 2019 (COVID-19) in Daegu, Korea, aftermath of the largest epicenter in Korea. The study is in line with previous assumptions that there may had been a large transmission of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting asymptomatic infection in the general population. However, a few points should be clarified prior to drawing conclusions.
First, the performance of the antibody assay that was used in the study should be noted. The clinical specificity of assays should be vigorously evaluated before applying to the large-scale evaluation of a population. The authors described the specificity of the assay as 92%, which the number may not be drawn from 30 specimens. If the specificity is 92%, which means that false-positive rate is 8%, the prevalence of 7.6% can be attributed to false-positive results, not from past-infection. The authors have assumed that moderate performance is acceptable in estimating the seroprevalence in population. However, even if the performance obtained from study is adequate, the application of the assay into general population should be cautious. The positive predictive value of diagnostic assays is affected by the disease prevalence.2 Low prevalence may result in a high false positive rate, or a low positive predictive value, vice versa.
Second, the property of the assay used should be taken into account in drawing the conclusion. The assays employed two antigens (nucleocapsid protein and receptor binding domain of spike protein). There is a report about the SARS-CoV-2 antibody tests using multiple antigens to increase specificity.3 In this report, when a sample was assessed as positive when reacted with either of multiple antigens, the test specificity has decreased. The assay that authors used multiple antigens in single reaction and cannot differentiate between two antigens. Therefore, this property may lower the specificity of assay. Even though authors might declare that the specificity of the assays was 100%, the variation of performance among COVID-19 antibody based on lateral flow immunoassay was reported to be high and the variation among the interpreters was also high.456
Third, although the authors have acknowledged selection bias, they should recognize that the patient group had more of health-related issues compared with general population, resulting limited generalizability of the study. The generalization of the prevalence obtained from patient group should be cautious. A recent systematic review found that 89% of antibody test evaluation results had selection bias.4 In addition, the PCR-negative specimens collected during COVID-19 pandemic period are inadequate for the evaluation of specificity, as the convalescent patients may show positive results in antibody assay, but negative results in PCR.7 If the authors claimed the high seroprevalence in the population, then authors should not use the PCR-negative samples from the population as negative control group. Moreover, given only small specimens have been included (60 positive and 30 negative), providing the confidence intervals for distribution would be more informative. The confidence interval of the specificity seems to be 88.4%–100.0%, based on Clopper-Pearson Interval.
The authors have estimated the “actual number” of SARS-CoV-2 infection in Daegu to be greater than 180,000 persons, which may be misled from the intrinsic limitation of the study. They also have stated several interesting opinions such as the limited value of containment and the limited role of antibody assay in selecting donor for plasma therapy. However, the points that we have mentioned above should be clarified before drawing the conclusion of the study.
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