Performance of Various Lateral Flow SARS-CoV-2 Antigen Self Testing Methods in Healthcare Workers: a Multicenter Study. (preprint)

Introduction: Rapid antigen detection tests (RDT) are suitable for large-scale testing for SARS-CoV-2 among the population and recent studies have shown that self-testing with RDT in the general population is feasible and yields acceptable sensitivities with high specificity. We aimed to determine the accuracy of two different RDT, with two different sample collection methods for one of the RDT among healthcare workers (HCW). Secondary objectives were to determine the accuracy of RDT using a viral load cut-off as proxy of infectiousness and to identify predictors for a false negative RDT. Methods: Centers that participated were secondary care hospitals, academic teaching hospitals, and long-term care facilities. All HCW that met inclusion criteria were asked to perform a RDT self-test next to a regular SARS-CoV-2 nucleic acid amplification test (NAAT). Three study groups were created. Study group 1; Veritor System, Becton Dickinson, Franklin Lakes, USA (BD-RDT) with combined oropharyngeal - mid-turbinate nasal sampling, group 2; BD-RDT with mid-turbinate nasal sampling only and group 3; SD Biosensor SARS-CoV-2 Rapid Antigen Test, Roche, Basel, Switzerland (Roche-RDT) with combined oropharyngeal - mid-turbinate nasal sampling. RDT accuracy was calculated using NAAT as reference standard. For samples processed in the cobas(R) 6800/8800 platform (Roche Diagnostics, Basel, Switzerland), established cycle threshold values (Ct-values) could be converted into viral loads. A viral load cut-off of [≥]5.2 log10 SARS-CoV-2 E gene copies/ml was used as proxy of infectiousness. Logistic regression analysis was performed to identify predictors for a false negative RDT. Results: In total, 7,196 HCW were included. Calculated sensitivities were 61.5% (95%CI 56.6%-66.3%), 50.3% (95%CI 42.8%-57.7%) and 74.2% (95%CI 66.4%-80.9%) for study groups 1, 2 and 3, respectively. After application of a viral load cut-off as a proxy for infectiousness for samples processed in the cobas(R) 6800/8800 platform sensitivities increased to 82.2% (95%CI 76.6-86.9%), 61.9% (95%CI 48.8%-73.9%) and 90.2% (95%CI 76.9%-97.3%) for group 1, group 2 and group 3, respectively. Multivariable regression analysis showed that use of Roche-RDT (p <0.01), combined oropharyngeal - mid-turbinate nasal sampling (p <0.05) and the presence of COVID-19 like symptoms at the time of testing (p <0.01) significantly reduced the likeliness of a false-negative RDT result. Conclusion: SARS-CoV-2 RDT has proven able to identify infectious individuals, especially when upper respiratory specimen is collected through combined oropharyngeal - mid-turbinate sampling. Reliability of self-testing with RDT among HCW seems to depend on the type of RDT, the sampling method and the presence of COVID-19 like symptoms at the time of testing.

COVID-19 in healthcare workers in three hospitals in the South of the Netherlands, March 2020 (preprint)

Background: Ten days after the first reported case of SARS-CoV-2 infection in the Netherlands, 3.9% of healthcare workers (HCWs) in nine hospitals located in the South of the Netherlands tested positive for SARS-CoV-2 RNA. The extent of nosocomial transmission that contributed to the HCW infections was unknown. Methods: We combined epidemiological data, collected by means of structured interviews of HCWs, with whole genome sequencing (WGS) of SARS-CoV-2 in clinical samples from HCWs and patients in three of nine hospitals that participated in the HCW screening, to perform an in-depth analysis of sources and modes of transmission of SARS -CoV-2 in HCWs and patients. Results: A total of 1,796 out of 12,022 HCWs (15%) of the three participating hospitals were screened, based on clinical symptoms, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete genome sequences of 50 HCWs and 18 patients. Most sequences grouped in 3 clusters, with 2 clusters displaying local circulation within the region. The observed patterns are most consistent with multiple introductions into the hospitals through community acquired infections, and local amplification in the community. Conclusions: Although direct transmission in the hospitals cannot be ruled out, the data does not support widespread nosocomial transmission as source of infection in patients or healthcare workers.