The big data analysis application to evaluate the clinical utility of igm anti sars-cov-2 determination: the experience of modena

ABSTRACT

Background: Serological tests identifying SARS-CoV-2 IgG and IgM in serum play an important role in understanding the disease epidemiology. However, their immunological significance are currently undefined. There are many methods available for the detection of specific Abs whit suboptimal diagnostic accuracy and relatively high throughput capacity and less stringent specimen requirements compared to RNA-based assays. We aimed to assess the clinical utility of IgM detection in SARSCoV- 2 using the big data analysis. Methods: We conduct a retrospective study analyzing with a big data analysis all samples collected between 11 March and 30 September 2020. All serum samples received at the laboratory were processed using qualitative and commercially available rapid lateral flow immunoassay tests for 2019-nCoV IgG and IgM. Positive results were confirmed using a chemiluminescent method. Subjects with a positive result were contacted from the Department of Public Health for further tests (viral RNA research or subsequent serological tests) for definitive diagnosis.Results: A total of 69,343 serological tests (in 42,911 subjects) and 140,065 oropharyngeal or nasopharyngeal swabs (in 88,771 subjects) were performed. 94.5% of subjects screened (n=40,559) had negative results for both IgG and IgM. Of the 640 subjects with both IgG and IgM positive results, viral RNA research confirmed positivity in 16%. Of the subjects with IgG negative and IgM positive results, a positivity was confirmed in 1.4% (n=7/478) subjects. Subsequent serological testing confirmed IgG positivity in 8 subjects (1.6%). Conversely, in subjects with IgG positive and IgM negative results, a positivity was confirmed in 7.9%. Therefore, analysis suggests that up to 94% of serological test results of IgM positivity and IgG negativity are false positive whereas, serological test results of IgG positive and IgM negative are confirmed true positives in around 7.9% of subjects. Discussion: Our study, based on big data analysis application, confirms the scarce clinical utility of IgM anti SARS-CoV-2 detection in COVID-19 management, and underlines the responsibility of laboratory medicine professionals to highlight limitations of the SARS-CoV-2 serological tests due to uncertainty in their interpretation.