BACKGROUND. In the COVID-19 pandemic, highly selective serological testing is essential to define exposure to SARS-CoV-2 virus. Many tests have been developed, yet with variable speed to first result, and of unknown quality, particularly when considering the prediction of neutralizing capacity. OBJECTIVES/METHODS. The LIAISON® SARS-CoV-2 S1/S2 IgG assay was designed to measure antibodies against the SARS-CoV-2 native S1/S2 proteins in a standardized automated chemiluminescent assay. Clinical and analytical performance of the test were validated in an observational study using residual samples (>1500) with positive or negative COVID-19 diagnosis. RESULTS. The LIAISON® SARS-CoV-2 S1/S2 IgG assay proved to be highly selective and specific, and offers semiquantitative measures of serum or plasma levels of anti-S1/S2 IgG with neutralizing activity. The assay's diagnostic sensitivity was 91.3% and 95.7% at >5 or ≥15 days from diagnosis, respectively, and 100% when assessed against a neutralizing assay. The assay's specificity ranged between 97% and 98.5%. The average imprecision of the assay was <5 % coefficient of variation. Assay performance at 2 different cut-offs was evaluated to optimize predictive values. CONCLUSIONS. The automated LIAISON® SARS-CoV-2 S1/S2 IgG assay brings efficient, sensitive, specific, and precise serological testing to the laboratory, with the capacity to test large amounts of samples per day: first results are available within 35 minutes with a throughput of 170 tests/hour. The semiquantitative results provided by the test also associate with the presence of neutralizing antibodies, and may provide a useful tool for the large scale screening of convalescent plasma for safe therapeutic use.

This analysis, despite inevitable inherent limitations, introduces several clinical implications. First, median 25-OHD-dependent PTH levels revealed no threshold above which increasing 25-OHD fails to further suppress PTH. Second, the large number of subjects with 25-OHD deficiency and hyperparathyroidism reinforces the Third International Workshop on Asymptomatic Primary Hyper parathyroidism's recommendations to test for, and replete, vitamin D depletion before considering parathyroidectomy. Third, strong age dependency of the PTH-25-OHD relationship likely reflects the composite effects of age-related decline in calcium absorption and renal function. Finally, this unselected large population database study could guide clinical management of patients based on an age-dependent, PTH-25-OHD continuum.

Objectives COVID-19 has brought about tests from many manufacturers. While molecular and rapid antigen tests are targeted for early diagnosis, immunoassays have a larger role in epidemiological studies, understanding longitudinal immunity, and in vaccine development and response. Methods The performance of the LIAISON® SARS-CoV-2 TrimericS IgG assay was evaluated against the Beckman ACCESS SARS-CoV-2 IgG assay in New Mexico, and against the Siemens ADVIA Centaur COV2G assay in New York. Discordant samples were parsed using a microneutralization assay. Results A SARS-CoV-2 antibody positivity rate of 23.8% was observed in the samples tested in New York (September 2020), while in the same month the positivity rate was 1.5% in New Mexico. Positive and negative agreement were 67.6% (95% CI 49.5–82.6%) and 99.8% (95% CI 99.5–99.9%), respectively, with the Beckman test, and 98.0% (95% CI 95.7–99.3%) and 94.8% (95% CI 93.4–96.0%), respectively, with the Siemens test. Receiver operating characteristic analysis for the detection of SARS-CoV-2 antibodies discloses an AUC, area under the curve, of 0.996 (95% CI 0.992–0.999) for the LIAISON® SARS-CoV-2 TrimericS IgG assay. The criterion associated to the Youden Index was determined to be >12.9 kAU/L with a sensitivity of 99.44% and a specificity of 99.82%. Conclusions The LIAISON® SARS-CoV-2 TrimericS IgG assay is highly sensitive and specific. The balance of these parameters, without emphasis on high specificity alone, is particularly important when applied to high prevalence populations, where a highly sensitive assay will result in reporting a lower number of false negative subjects.

word count: 246 20 Text word count: 3188 21 22 4 ABSTRACT 23BACKGROUND. In the Covid-19 pandemic, highly selective serological testing is 24 essential to define exposure to SARS-CoV-2 virus. Many tests have been developed, 25 yet with variable speed to first result, and of unknown quality, particularly when 26 considering the prediction of neutralizing capacity. 27 OBJECTIVES/METHODS. The LIAISON ® SARS-CoV-2 S1/S2 IgG assay was designed 28 to measure antibodies against the SARS-CoV-2 native S1/S2 proteins in a standardized 29 automated chemiluminescent assay. Clinical and analytical performance of the test 30 were validated in an observational study using residual samples (>1500) with positive or 31 negative Covid-19 diagnosis. 32RESULTS. The LIAISON ® SARS-CoV-2 S1/S2 IgG assay proved highly selective and 33 specific, and offers semiquantitative measures of serum or plasma levels of anti-S1/S2 34 IgG with neutralizing activity. The diagnostic sensitivity was 91.3% and 95.7% at >5 or 35 ≥15 days from diagnosis respectively, and 100% when assessed against a neutralizing 36 assay. The specificity ranged between 97% and 98.5%. The average imprecision of the 37 assay was <5 % coefficient of variation. Assay performance at 2 different cut-offs was 38 evaluated to optimize predictive values in settings with different % disease prevalence. 39 CONCLUSIONS. The automated LIAISON ® SARS-CoV-2 S1/S2 IgG assay brings 40 efficient, sensitive, specific, and precise serological testing to the laboratory, with the 41 capacity to test large amounts of samples per day: first results are available within 35 42 minutes with a throughput of 170 tests/hour. The test also provides a semiquantitative 43 measure to identify samples with neutralizing antibodies, useful also for a large scale 44 screening of convalescent plasma for safe therapeutic use. 45 5 IMPORTANCE 46With the worldwide advance of the COVID-19 pandemic, efficient, reliable and 47 accessible diagnostic tools are needed to support public health officials and healthcare 48 providers in their efforts to deliver optimal medical care, and articulate sound 49 demographic policy. DiaSorin has developed an automated serology based assay for 50 the measurement of IgG specific to SARS CoV-2 Spike protein, and tested its clinical 51 performance in collaboration with Italian health care professionals who provided access 52 to large numbers of samples from infected and non-infected individuals. The assay 53 delivers excellent sensitivity and specificity, and is able to identify samples with high 54 levels of neutralizing antibodies. This will provide guidance in assessing the true 55 immune status of subjects, as well as meeting the pressing need to screen donors for 56 high titer convalescent sera for subsequent therapeutic and prophylactic use. 57 58 SARS-CoV-2, the virus responsible for the Covid-19 pandemic, has spread at an 59 alarming rate since the first case tracked back to mid-November of 2019 in Wuhan 60 China (1). Contraction and subsequent transmission accrue...

Mammals have separate enzymatic and cellularly mediated detoxification systems. Glutathione S-transferases (GSTs) protect against xenobiotic chemicals which continuously enter the body, largely through mucous membranes. These enzymes catalyse the conjugation of glutathione with a wide variety of electrophilic compounds rendering them non-toxic. Mammals also mount a cellular immunological response on entry of foreign cells, viruses or macromolecules into the body. T lymphocytes mobilize at the site of foreign body entry and secrete protein messengers called lymphokines. Secondary to T lymphocytes, macrophages concentrate at the infection site and function in antigen processing and phagocytosis. In vitro, macrophage movement is arrested by one class of lymphokines known as macrophage migration inhibitory factors (MIFs). We report here the purification of milligram quantities of a unique multifunctional protein from rat liver which links enzymatic and immunological detoxification systems. This protein actuates both GST and MIF activity and matches the primary structure of a human MIF in 25 out of 26 amino-terminal amino acids. Primary structure comparisons revealed significant similarity between GSTs and MIF. The glutathione affinity chromatography purification described here yields a 100-fold increase in obtaining MIF and will aid understanding of its precise biological function.