Pooled analysis of laboratory-based SARS-CoV-2 antigen immunoassays

Joint efforts of the IFCC Task Force on COVID-19 and IFCC Working Group on SARS-CoV-2 variants have enabled to publish a series of critical literature reviews and meta-analyses, providing summary statistics of diagnostic accuracy of most of the currently commercially available laboratory-based SARS-CoV-2 immunoassays. In this short report we provide a brief overview of all such reports, compounded by a pooled analysis of their individual diagnostic performance. Overall, 58 individual studies and 28,916 respiratory samples could be included in our pooled analysis. The area under the curve (AUC) and accuracy were 0.978 and 0.92, with 0.74 sensitivity and 0.98 specificity. The PPV and NPV were instead 0.93 and 0.91, respectively. Importantly, for the four laboratory-based SARS-CoV-2 immunoassays for which sufficient data were available in respiratory samples with high viral load (21 pooled studies; 1570 respiratory samples), the diagnostic sensitivity increased to 0.87 (95%CI, 0.85-0.89). In conclusion, although we proffer that laboratory-based immunoassays are not reliable and accurate enough for completely replacing molecular detection of SARS-CoV-2 RNA for purposes of diagnosing acute infections to date, they could be more pragmatically employed for screening and identifying patients with higher SARS-CoV-2 viral load, especially in all circumstances where contagion is more likely to occur (i.e., mass gatherings, indoor meetings without using physical protective measures like glasses, face masks or social distancing), or where high infectivity is more likely to generate substantial harm in secondary cases (i.e., fragile and more vulnerable individuals such as those older, immunocompromised or bearing important medical conditions).