Decreased Sensitivity of Rapid Antigen Test Is Associated with a Lower Viral Load of Omicron than Delta SARS-CoV-2 Variant.

Large-scale screening for SARS-CoV-2 infection is an important tool for epidemic prevention and control. The appearance of new variants associated with specific mutations can call into question the effectiveness of rapid diagnostic tests (RDTs) deployed massively at national and international levels. We compared the clinical and virological characteristics of individuals infected by Delta or Omicron variants to assess which factors were associated with a reduced performance of RDT. A commercially available RDT as well as the evaluation of the viral load (VL) and the detection of replicate intermediates (RIs) were carried out retrospectively on positive SARS-CoV-2 nasopharyngeal specimens from health care workers of the Pitié-Salpêtrière Hospital infected by the Delta or Omicron variant between July 2021 and January 2022. Of the 205 samples analyzed (104 from individuals infected with Delta and 101 with Omicron), 176 were analyzed by RDT and 200 by RT-PCR for VL and RIs. The sensitivity of the TDR for Omicron was significantly lower than that observed for Delta (53.8% versus 74.7%, respectively, P < 0.01). Moreover, the Delta VL was significantly higher than that measured for Omicron (median Ct 21.2 versus 24.1, respectively, P < 0.01) and associated with the positivity of the RDT in multivariate analysis. We demonstrate a lower RDT sensitivity associated with a lower VL at the time of diagnosis on Omicron-infected individuals in comparison to those infected with the Delta variant. This RDT lower sensitivity should be taken into account in the large-scale screening strategy and in particular in case of strong suspicion of infection where testing should be repeated. IMPORTANCE Previous reports have shown a variability in the diagnostic performance of RDTs. In the era of SARS-CoV-2 variants and the use of RDT, mutation associated with these variants could affect the test performance. We evaluate the sensitivity of the RDT Panbio COVID-19 Ag (Abbott) with two variants of concern (VOC), the Delta and Omicron variants. In order to investigate whether clinical characteristics or virological characteristics can affect this sensitivity, we collected clinical information and performed a specific RT-PCR that detected the RIs as a marker of the viral replication and viral cycle stage. Our results showed that Omicron was less detected than the Delta variant. A lower viral load of Omicron variant in comparison to Delta variant explained this decreased sensitivity, even if they are at the same stage of the disease and the viral cycle and should be taken into account with the use of RDT as diagnostic tool.

MAN1B1-CDG: Three new individuals and associated biochemical profiles.

Congenital disorders of glycosylation (CDG) constitute an ever-growing group of genetic diseases affecting the glycosylation of proteins. CDG individuals usually present with severe multisystem disorders. MAN1B1-CDG is a CDG with nonspecific clinical symptoms such as intellectual deficiency and developmental delay. Although up to 40 affected individuals were described so far, its final diagnosis is not straightforward using common biochemical methods due to the trace-level accumulation of defective glycan structures. In this study, we present three unreported MAN1B1-CDG individuals and propose a decision tree to reach diagnosis using a panel of techniques ranging from exome sequencing to gel electrophoresis and mass spectrometry. The occurrence of MAN1B1-CDG in patients showing unexplained intellectual disability and development delay, as well as a particular transferrin glycosylation profile, can be ascertained notably using matrix assisted laser desorption/ionization - time of flight (MALDI-TOF) mass spectrometry analysis of endo-ß-acetylglucosaminidase H-released serum N-glycans. In addition to reporting new pathogenic variants and additional clinical signs such as hypersialorrhea, we highlight particular biochemical features of MAN1B1-CDG with potential glycoprotein-specific glycosylation defects.