Development and Diagnosis Performance of IgM-Based Rapid Antigen Test for Early Detection of SARS-CoV-2 Infection in a Large Cohort of Suspected COVID-19 Cases - USA, Poland, and Sweden, 2021-2022.

INTRODUCTION: Antigen testing has been crucial in effectively managing the coronavirus disease 2019 (COVID-19) pandemic. This study evaluated the clinical performance of a nasopharyngeal swab (NPS)-based antigen rapid diagnostic test (Ag-RDT) compared to the gold standard real-time reverse transcription-polymerase chain reaction (RT-PCR) for early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We developed an IgM-based rapid antigen test for early detection of SARS-CoV-2 infection. Between July 2021 and January 2022, we analyzed 1,030 NPS samples from participants at three centers in different countries, using both antigen rapid diagnostic tests (Ag-RDT) and RT-PCR. RESULTS: The Ag-RDT demonstrated minimal detection limits as low as 0.1 ng/mL for recombinant N antigen and 100 TCID50/mL for heat-inactivated SARS-CoV-2 virus. Specificity assessments involving four human coronaviruses and 13 other respiratory viruses showed no cross-reactivity. The Ag-RDT assay (ALLtest) exhibited high sensitivity (93.18%-100%) and specificity (99.67%-100%) across all centers. Factors such as cycle threshold (Ct) values and the timing of symptoms since onset were influential, with sensitivity increasing at lower Ct values (<30) and within the first week of symptoms. CONCLUSION: The ALLtest Ag-RDT demonstrated high reliability and significant potential for diagnosing suspected COVID-19 cases.