Wide real-life data supports reduced sensitivity of antigen tests for Omicron SARS-CoV-2 infections

Background: with the continuous spread of new SARS-CoV-2 variants of concern (VOC), monitoring of diagnostic test performances is mandatory. This study aimed at evaluating the changes in the accuracy of antigen diagnostic tests (ADT) along Delta to Omicron VOCs transition, exploring also N protein mutations possibly affecting ADT sensitivity and assessing the best sampling site (nose or mouth) for the diagnosis of Omicron infections.

Methods: 5,175 patients referring to IRCCS Sacro Cuore Don Calabria Hospital (Italy) since October 1^ST 2021 to July 15^TH 2022 were included in the study. Inclusion criteria were SARS-CoV-2 ADT combined to reverse transcriptase polymerase chain reaction (RT-PCR) swab test, performed in the same day. For sampling site analysis, 61 subjects verified as positive to SARS-CoV-2 during the Omicron period were prospectively recruited for nose and mouth swab analysis by RT-PCR. Next Generation Sequencing data was obtained to evaluate the different sublineages.

Results: using RT-PCR as reference, the overall sensitivity of the ADT decreased from 64% in the Delta period to 33.3% in the Omicron period. This decrease was highly statistically significant (p<0.0001) and no difference in viral load levels were detected. The nose site presented significantly higher viral load respect to the mouth during the Omicron wave.

Conclusions: The reduced detection rate of Omicron infections by ADT should be considered in the global testing strategy, to preserve accurate diagnosis across the SARS-CoV-2 changing variants.