Introduction Numerous CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) are offered in Europe, several of them with unconfirmed quality claims. Aim We performed an independent head-to-head evaluation of the sensitivity of SARS-CoV-2 Ag RDT offered in Germany. Methods We addressed the sensitivity of 122 Ag RDT in direct comparison using a common evaluation panel comprised of 50 specimens. Minimum sensitivity of 75% for panel specimens with a PCR quantification cycle (Cq) ≤ 25 was used to identify Ag RDT eligible for reimbursement in the German healthcare system. Results The sensitivity of different SARS-CoV-2 Ag RDT varied over a wide range. The sensitivity limit of 75% for panel members with Cq ≤ 25 was met by 96 of the 122 tests evaluated; 26 tests exhibited lower sensitivity, few of which failed completely. Some RDT exhibited high sensitivity, e.g. 97.5 % for Cq < 30. Conclusions This comparative evaluation succeeded in distinguishing less sensitive from better performing Ag RDT. Most of the evaluated Ag RDT appeared to be suitable for fast identification of acute infections associated with high viral loads. Market access of SARS-CoV-2 Ag RDT should be based on minimal requirements for sensitivity and specificity.

Background Antibody detection of SARS-CoV-2 requires an understanding of its variation, course, and duration. Methods Antibody response to SARS-CoV-2 was evaluated over 5-430 days on 828 samples across COVID-19 severity levels, for total antibody (TAb), IgG, IgA, IgM, neutralizing antibody (NAb), antibody avidity, and for receptor-binding-domain (RBD), spike (S), or nucleoprotein (N). Specificity was determined on 676 pre-pandemic samples. Results Sensitivity at 30-60 days post symptom onset (pso) for TAb-S/RBD, TAb-N, IgG-S, IgG-N, IgA-S, IgM-RBD, and NAb was 96.6%, 99.5%, 89.7%, 94.3%, 80.9%, 76.9% and 92.8%, respectively. Follow-up 430 days pso revealed: TAb-S/RBD increased slightly (100.0%); TAb-N decreased slightly (97.1%); IgG-S and IgA-S decreased moderately (81.4%, 65.7%); NAb remained positive (94.3%), slightly decreasing in activity after 300 days; there was correlation with IgG-S (Rs=0.88) and IgA-S (Rs=0.71); IgG-N decreased significantly from day 120 (15.7%); IgM-RBD dropped after 30-60 days (22.9%). High antibody avidity developed against S/RBD steadily with time in 94.3% of patients after 430 days. This correlated with persistent antibody detection depending on antibody-binding efficiency of the test design. Severe COVID-19 correlated with earlier and higher antibody response, mild COVID-19 was heterogeneous with a wide range of antibody reactivities. Specificity of the tests was ≥99%, except for IgA (96%). Conclusion Sensitivity of anti-SARS-CoV-2 assays was determined by test design, target antigen, antibody avidity, and COVID-19 severity. Sustained antibody detection was mainly determined by avidity progression for RBD and S. Testing by TAb and for S/RBD provided the highest sensitivity and longest detection duration of 14 months so far.

SummarySamples from >750 patients with presumptive TB in two continents were tested with a field-based IgG serological assay incorporating 57 M. tuberculosis antigens, and showed that responses to single antigens or multiple antigen sets have no clinically useful discriminating power.

Patients carrying very rare loss‐of‐function mutations in interleukin‐1 receptor–associated kinase 4 (IRAK4), a critical signaling mediator in Toll‐like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon‐alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV). Cytokine production in response to purified Toll‐like receptor agonists was also impaired. Additionally, rs3844283 was epidemiologically associated with a chronic course of HCV infection in two independent HCV cohorts and emerged as an independent predictor of chronic HCV disease. Mechanistically, IRAK2 L392V showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor–associated factor 6, a vital step in signal transduction. Conclusion: Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity. (Hepatology 2015;62:1375–1387)