Vaccine-induced SARS-CoV-2 antibody response: the comparability of S1-specific binding assays depends on epitope and isotype discrimination.

Background: Quantification of the SARS-CoV-2-specific immune response by serological immunoassays is critical for the management of the COVID-19 pandemic. In particular, neutralizing antibody titers to the viral spike (S) protein have been proposed as a correlate of protection (CoP). The WHO established the First International Standard (WHO IS) for anti-SARS-CoV-2 immunoglobulin (Ig) (NIBSC 20/136) to harmonize binding assays with the same antigen specificity by assigning the same unitage in binding antibody units (BAU)/ml. Method: In this study, we analyzed the S1-specific antibody response in a cohort of healthcare workers in Germany (n = 76) during a three-dose vaccination course over 8.5 months. Subjects received either heterologous or homologous prime-boost vaccination with ChAdOx1 nCoV-19 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) or three doses of BNT162b2. Antibodies were quantified using three anti-S1 binding assays (ELISA, ECLIA, and PETIA) harmonized to the WHO IS. Serum levels of neutralizing antibodies were determined using a surrogate virus neutralization test (sVNT). Binding assays were compared using Spearman's rank correlation and Passing-Bablok regression. Findings: All assays showed good correlation and similar antibody kinetics correlating with neutralizing potential. However, the assays show large proportional differences in BAU/ml. ECLIA and PETIA, which detect total antibodies against the receptor- binding domain (RBD) within the S1 subunit, interact similarly with the convalescent plasma-derived WHO IS but differently with vaccine serum, indicating a high sensitivity to the IgG/IgM/IgA ratio. Conclusion: All three binding assays allow monitoring of the antibody response in COVID-19-vaccinated individuals. However, the assay-specific differences hinder the definition of a common protective threshold in BAU/ml. Our results highlight the need for the thoughtful use of conversion factors and consideration of method-specific differences. To improve the management of future pandemics and harmonize total antibody assays, we should strive for reference material with a well-characterized Ig isotype composition.

Clinical performance evaluation of a SARS-CoV-2 Rapid Antibody Test for determining past exposure to SARS-CoV-2.

OBJECTIVES: Due to the number of asymptomatic infections and limited access to high-performance antibody tests, the true prevalence and seropositivity of SARS-CoV-2 infection remains unknown. To fill this gap, the clinical performance of a point-of-care SARS-CoV-2 Rapid Antibody Assay, a chromatographic immunoassay for detecting IgM/IgG antibodies, in near patient settings was assessed. METHODS: Forty-two anti-SARS-Cov-2 positive (CoV+) and 92 anti-SARS-Cov-2 negative (CoV-) leftover samples from before December 2019 were assessed; the Elecsys® Anti-SARS-CoV-2 was used as the reference assay. Analytical specificity was tested using leftover samples collected before December 2019 from patients with common cold symptoms. RESULTS: The SARS-CoV-2 Rapid Antibody Test was 100.0% (95% CI 91.59-100.0) sensitive and 96.74% (95% CI 90.77-99.32) specific, with 0.00% assay failure rate. No cross-reactivity was observed against the common cold panel. Method comparison was additionally conducted by two external laboratories, using 100 CoV+ and 275 CoV- samples, also comparing whole blood versus plasma matrix. The comparison demonstrated 96.00% positive and 96.36% negative percent agreement for plasma with the Elecsys Anti-SARS-CoV-2 and 99.20% percent overall agreement between whole blood and EDTA plasma. CONCLUSION: The SARS-CoV-2 Rapid Antibody Test demonstrated similar performance to the manufacturer's data and a centralised automated immunoassay, with no cross-reactivity with common cold panels.

Thrombocytopenia after implantation of the Perceval S aortic bioprosthesis.

OBJECTIVE: The Perceval S bioprosthesis (LivaNova PLC, London, United Kingdom) is based on the Freedom Solo aortic bioprosthesis (LivaNova PLC), which has been reported to be associated with perioperative thrombocytopenia. We compared platelet counts after aortic valve replacement with the Perceval S with those with other aortic valve bioprostheses. METHODS: A total of 87 patients receiving aortic valve replacement were included in this retrospective study; 25 patients received the Perceval S, 23 patients received the Labcor TLPB-A (Labcor, Belo Horizonte, Brazil), and 39 patients received the Hancock II bioprosthesis (Medtronic, Minneapolis, Minn). Thrombocyte count was corrected for hematocrit. Multivariable analyses were performed to assess the potential effect of other variables. RESULTS: Preoperatively, there were no differences in platelet counts comparing the Perceval S group (median 200/nl, interquartile range, 157-252) and the control group (Labcor: median 213/nl, interquartile range, 160-246, Hancock: median 227/nl, interquartile range, 183-280, P = .23). Postoperatively, there was significant evidence that the minimum platelet count (median, Perceval: 47, interquartile range, 38-66; Labcor: 76, interquartile range, 61-110; Hancock: 78, interquartile range, 61-111/nl; P = .001), both absolute and corrected, was lower for the Perceval S, even after allowing for other variables. The significant difference in absolute platelet counts persisted until discharge or death. However, there were no significant differences regarding blood loss, transfusion requirements, or rates of reoperation for bleeding. CONCLUSIONS: After aortic valve replacement, platelet counts in patients with the Perceval S decrease more severely compared with other bioprostheses, but in our small study we found no evidence of a detrimental clinical effect of this phenomenon. Future studies have to confirm our findings and investigate a cause for this phenomenon.

Influence of welding fume on systemic iron status.

Iron is the major metal found in welding fumes, and although it is an essential trace element, its overload causes toxicity due to Fenton reactions. To avoid oxidative damage, excess iron is bound to ferritin, and as a result, serum ferritin (SF) is a recognized biomarker for iron stores, with high concentrations linked to inflammation and potentially also cancer. However, little is known about iron overload in welders. Within this study, we assessed the iron status and quantitative associations between airborne iron, body iron stores, and iron homeostasis in 192 welders not wearing dust masks. Welders were equipped with personal samplers in order to determine the levels of respirable iron in the breathing zone during a working shift. SF, prohepcidin and other markers of iron status were determined in blood samples collected after shift. The impact of iron exposure and other factors on SF and prohepcidin were estimated using multiple regression models. Our results indicate that respirable iron is a significant predictor of SF and prohepcidin. Concentrations of SF varied according to the welding technique and respiratory protection used, with a median of 103 µg l(-1) in tungsten inert gas welders, 125 µg l(-1) in those wearing air-purifying respirators, and 161 µg l(-1) in other welders. Compared to welders with low iron stores (SF < 25 µg l(-1)), those with excess body iron (SF ≥ 400 µg l(-1)) worked under a higher median concentration of airborne iron (60 µg m(-3) versus 148 µg m(-3)). Even though air concentrations of respirable iron and manganese were highly correlated, and low iron stores have been reported to increase manganese uptake in the gastrointestinal tract, no correlation was seen between SF and manganese in blood. In conclusion, monitoring SF may be a reasonable method for health surveillance of welders. Respiratory protection with air-purifying respirators can decrease iron exposure and avoid chronically higher SF in welders working with high-emission technologies.

Increased preoperative serum apoptosis marker fas ligand correlates with histopathology and new-onset of atrial fibrillation in patients after cardiac surgery.

BACKGROUND: We evaluated if preoperative serum apoptosis markers correlate with atrial histological remodeling and postoperative atrial fibrillation (POAF) after cardiac surgery. METHODS AND RESULTS: A total of 33 patients with sinus rhythm (SR) and without history of atrial fibrillation (AF) undergoing cardiac surgery were prospectively enrolled. Serum concentrations of Fas (apoptosis-stimulating fragment ligand) and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) were measured preoperatively. Right atrial appendage (RAA) tissue was obtained during surgery. Atrial apoptosis was assessed via TUNEL assay and degree of atrial fibrosis was categorized histologically by visual quantification. Continuous ECG-Monitoring was used to screen for POAF throughout 10 days after cardiac surgery. POAF occurred in 15 patients (45%). Atrial apoptosis was higher in patients with POAF as compared to those without (35.9 ± 9.8% vs 14.5 ± 7.5%; P < 0.0001) and correlated with the degree of atrial fibrosis (r = 0.69; P < 0.0001). In contrast to TRAIL (87.0 ± 8.2 pg/mL vs 83.3 ± 9.4 pg/mL; P = 0.77), preoperative Fas serum concentration was significantly higher in patients with POAF compared to patients in stable SR (91.3 ± 7.2 pg/mL vs 66.7 ± 3.0 pg/mL; P < 0.01). Serum Fas concentration correlated with the degree of atrial apoptosis (r = 0.63; P < 0.001) and the degree of atrial fibrosis (r = 0.39; P < 0.05). CONCLUSION: Preoperative evaluation of serum apoptosis marker Fas is useful to identify patients at risk for POAF undergoing cardiac surgery. Fas but not TRAIL correlates with the documented degree of atrial apoptosis and atrial fibrosis in RAA tissue. Further studies need to identify the prospective role of Fas in predicting POAF events.