AZD7442 (150 mg of tixagevimab plus 150 mg of cilgavimab) has been approved for the preexposure prophylaxis of COVID‐19 and for the treatment of adults and adolescents with COVID‐19 who do not require supplemental oxygen and who are at increased risk of severe COVID‐19. Thus, the aim of the present study is to evaluate the neutralizing capacity of tixagevimab and cilgavimab across different SARS‐CoV‐2 variants in two patients who received AZD7442 for immunoprophylaxis. A cohort of subjects (n = 45) who had received the BNT162b2 mRNA COVID‐19 vaccine has been included to compare these two preventive strategies. Neutralizing antibody (NAb) titers against several variants were assessed against the wild‐type, alpha, beta, gamma, delta, omicron BA.5, and XBB.1.5 variants. Binding antibodies have also been measured. NAbs T1/2 for AZD7442 was 8.1 days (95% CI: 5.1–19.5 days) and was 11.8 days (95% CI: 7.9–23.7 days) for the primo‐vaccination cohort. The time to reach neutralization negativity was 108.3 days (95% CI: 66.9–130.7) for AZD7442 compared to 95.4 days (95% CI: 31.0–119.7 days) for the primo‐vaccination cohort. The time to reach NAbs’ negativity differs between variants with the maximum value obtained for alpha (i.e., 101.1 days (95% CI: 30.0–135.4 days)) and the minimum obtained for beta (i.e., 61.2 days (95% CI: 37.8–77.1 days)). Our results reinforce the need of reviewing the use of AZD7442 in relation to variants of concern and potentially adapting its administration schedule. AZD7442 could be indicated for short‐term prophylaxis in frail patients who may be acutely exposed to SARS‐CoV‐2.

Background: The detection of neutralizing anti-SARS-CoV-2 antibodies is important since they represent the subset of antibodies able to prevent the virus to invade human cells. The aim of this study is to evaluate the clinical performances of an in-house pseudovirus neutralization test (pVNT) versus a commercial surrogate neutralization test (sVNT). Material and Methods: A total of 114 RT-PCR positives samples from 75 COVID-19 patients were analyzed using a pVNT and an sVNT technique. Fifty-six pre-pandemic samples were also analyzed to assess the specificity of the two techniques. An analysis of the repeatability and the reproducibility of the pVNT was also performed. Results: A coefficient of variation (CV) of 10.27% for the repeatability of the pVNT was computed. For the reproducibility test, CVs ranged from 16.12% for low NAbs titer to 6.40% for high NAbs titer. Regarding the clinical sensitivity, 90 RT-PCR positive samples out of 114 were positive with the pVNT (78.94%), and 97 were positive with the sVNT (84.21%). About the clinical specificity, all 56 pre-pandemic samples were negative in both techniques. When comparing the sVNT to the pVNT, the specificity and sensibility were 66.67% (95%CI: 47.81–85.53%) and 98.88% (95%CI: 96.72–99.99%), respectively. Conclusions: The results obtained with the automated sVNT technique are consistent with those obtained with the pVNT technique developed in-house. The results of the various repeatability and reproducibility tests demonstrate the good robustness of the fully manual pVNT technique.

Abstract Objectives The BNT162b2 messenger RNA vaccine is highly effective in reducing COVID‐19 infection, hospitalization and death. However, many subjects developed a breakthrough infection despite a full vaccination scheme. Since the waned efficacy of mRNA vaccines is correlated with the decrease of antibodies occurring over time, we aimed at evaluating whether lower levels of antibodies were associated with an increased risk of breakthrough infection in a cohort of breakthrough subjects that received three vaccine doses. Methods Total binding antibodies against the RBD of the S1 subunit (Roche Diagnostics, Machelen, Belgium) and neutralizing antibodies using the Omicron B.1.1.529 variant pseudovirus were measured. Based on individual kinetic curves, the antibody titer of each subject was interpolated just before the breakthrough infection and compared to a matched-control group that did not develop a breakthrough infection. Results Lower levels of total binding and neutralizing antibodies were observed compared to the control group (6.900 [95% CI; 5.101–9.470] vs. 11.395 BAU/mL [8.627–15.050] [p=0.0301] and 26.6 [18.0–39.3] vs. 59.5 dilution titer−1 [32.3–110] [p=0.0042], respectively). The difference between breakthrough and control subjects was mostly observed for neutralizing antibodies before three months after the homologous booster administration (46.5 [18.2–119] vs. 381 [285–509] [p=0.0156]). Considering the measurement of total binding antibodies before 3 months, there was no significant difference (p=0.4375). Conclusions In conclusion, our results showed that subjects that developed a breakthrough infection had lower levels of neutralizing and total binding antibodies compared to controls. The difference was mostly noticeable considering neutralizing antibodies, especially for infections occurring before 3 months after the booster administration.

AZD7442 (150 mg of tixagevimab plus 150 mg cilgavimab) has been approved for the pre-exposure prophylaxis of COVID-19 and for the treatment of adults and adolescents with COVID-19 who do not require supplemental oxygen and who are at increased risk of severe COVID-19. In this study, two patients received AZD7442 for immunoprophylaxis. A cohort of subject who had received the BNT162b2 mRNA COVID‐19 vaccine has been included to compare strategies. Neutralizing antibodies (NAbs) against several variants were measured (wild-type, Alpha, Beta, Gamma, Delta, Omicron BA.5 and XBB.1.5). Binding antibodies have also been measured. NAbs T 1/2 for AZD7442 was 8.1 days (95% CI: 5.1–19.5 days) and was 11.8 days (95% CI: 7.9–23.7 days) for the primo-vaccination cohort. The time to reach NAbs negativity was 108.3 days (95% CI: 66.9–130.7) for AZD7442 compared to 95.4 days (95% CI: 31.0–119.7 days) for primo-vaccination cohort. The time to reach NAbs negativity differs between variants with the maximum value obtained for the Alpha (i.e., 101.1 days (95% CI: 30.0–135.4 days)) and the minimum obtained for the Beta (i.e., 61.2 days (95% CI: 37.8–77.1 days)). Our results reinforces the need of reviewing the use of AZD7442 in relation to variant of concern and potentially adapting its administration schedule. AZD7442 could be indicated for short-term prophylaxis in frail patients who may be acutely exposed to SARS-CoV-2.

Neutralizing antibodies (NAbs) are of particular importance because they can prevent binding of the receptor binding domain (RBD) of the spike protein (S protein) to the angiotensin-converting enzyme 2 (ACE2) receptor present at the surface of human cells, preventing virus entry into the host cells. The gold standard method for detection of NAbs is the plaque reduction neutralization test (PRNT). Based on the measurement of cell lysis due to viral infection, this test is able to detect antibodies that prevent cell infection (Muruato et al., 2020; Lau et al., 2021). This technique requires the use of live pathogens, i.e., SARS-CoV-2 in this case, and must be done in a biosafety level 3 (BL3) laboratory. In addition, it requires expensive installations, skillful and meticulous staff, and a high workload, which prevents its wide implementation even in research laboratories. A SARS-CoV-2 pseudovirus will express the S protein responsible for cell entrance, but will not express the pathogenic genetic material of the virus, making them less dangerous for laboratory staff and the environment. Graphic abstract.

Hospital-acquired infections are responsible for a significant part of morbidity and mortality. Among the possible modes of transmission, this study focuses on environmental surfaces by developing innovative antibacterial coatings that can be applied on interior fittings in hospitals. This work aims to optimize a coating made of an amorphous carbon matrix doped with silver (a-C:H:Ag) produced by a hybrid PVD/PECVD process and to evaluate its antibacterial activity. We present a coating characterization (chemical composition and morphology) as well as its stability in an ageing process and after multiple exposures to bacteria. The antibacterial activity of the coatings is demonstrated against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria through several bioassays. Moreover, the data suggest a crucial role of silver diffusion towards the surface and nanoparticle formation to explain the very promising anti-bacterial activities reported in this work.

Introduction Edoxaban is the only anti-Xa inhibitor metabolized in pharmacologically active moiety that could interfere with chromogenic anti-Xa assays, especially in case of drug-drug interactions or physiological disorders. Materials and methods We evaluated the contribution of the main metabolite of edoxaban, edoxaban-M4 (M4), in 79 plasma samples from patients taking edoxaban. The total anti-Xa activity was evaluated on three different chromogenic factor Xa-based assays. Results were compared with a validated ultra-high-performance liquid chromatography coupled with a tandem mass spectrometry measurement. Edoxaban and its active M4 metabolite have also been spiked separately in normal pooled plasma to assess the sensitivity of chromogenic anti-Xa assays to both molecules individually. Results Spiked edoxaban or M4 provided different slopes of linear regression models between chromogenic and chromatographic measurement (from 0.97 for STA Liquid Anti-Xa to 1.10 for Biophen Heparin LRT Low with edoxaban and from 0.70 for Biophen DiXaI High to 0.83 for Biophen Heparin LRT High, respectively). A positive correlation is observed between the increase of the ratio M4/edoxaban with the difference between chromogenic and chromatographic measurements. Conclusion Edoxaban and M4 do not similarly impact chromogenic assays, leading to biased chromogenic estimations of ponderal concentrations. In patient samples, this impact is even more important at low concentrations or in the case of an increase in the M4/edoxaban ratio because of hepatic or renal impairments or in case of drug interactions. This study highlights the limitations and risks of error of expressing results in ponderal concentrations instead of global activity anti-Xa.

Background: in this report, we describe the case of an 83-year-old woman vaccinated with ChadOx1 nCoV-19 who developed a so-called vaccine-induced thrombosis with thrombocytopenia syndrome and who did not develop any antibodies against the spike protein of SARS-CoV-2 at 30 days following the administration of her first dose of ChadOx1 nCoV-19. Experimental section: two serum samples from the patient and 5 serum samples from 5 control individuals having received the two-dose regimen vaccination with ChadOx1 nCoV-19 were evaluated. In order to investigate the lack of response to the vaccination, a cell model was developed. This model permits to evaluate the interaction between responsive cells (A549) possessing the Coxsackievirus and Adenovirus Receptor (CAR), a defined concentration of ChadOx1 nCoV-19 and serial dilution of the patient or the control serum. The aim was to assess the impact of these sera on the production of the spike (S) protein induced by the transfection of the genetic material of ChadOx1 nCoV-19 into the A549 cells. The S protein is measured in the supernatant using an ELISA technique. Results: interestingly, the serum from the patient who developed the vaccine-induced thrombosis with thrombocytopenia syndrome impaired the production of S protein by the A549 cells transfected with ChadOx1 nCoV-19. This was not observed with the controls who did not interfere with the transfection of ChadOx1 nCoV-19 into A549 cells since the S protein is retrieved in the supernatant fraction. Conclusion: based on the data coming from the clinical and the cell model information, we found a possible explanation on the absence of antibody response in our patient. She has, or has developed, characteristics that prevent the production of the S protein in contrast to control subjects. We were not able to investigate the entire mechanism behind this resistance which deserve further investigations. A link between this resistance and the development of the thrombosis with thrombocytopenia syndrome following vaccination with ChadOx1 nCoV-19 cannot be excluded.

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Neutralising antibodies (NAbs) represent the real source of protection against SARS-CoV-2 infections by preventing the virus from entering target cells. The gold standard in the detection of these antibodies is the plaque reduction neutralization test (PRNT). As these experiments must be done in a very secure environment, other techniques based on pseudoviruses: pseudovirus neutralization test (pVNT) or surrogate virus neutralization test (sVNT) have been developed. Binding assays, on the other hand, measure total antibodies or IgG, IgM, and IgA directed against one epitope of the SARS-CoV-2, independently of their neutralizing capacity. The aim of this study is to compare the performance of six commercial binding assays to the pVNT and sVNT. In this study, we used blood samples from a cohort of 62 RT-PCR confirmed COVID-19 patients. Based on the results of the neutralizing assays, adapted cut-offs for the binding assays were calculated. The use of these adapted cut-offs does not permit to improve the accuracy of the serological assays and we did not find an adapted cut-off able to improve the capacity of these tests to detect NAbs. For a part of the population, a longitudinal follow-up with at least two samples for the same patient was performed. From day 14 to day 291, more than 75% of the samples were positive for NAbs (n = 87/110, 79.1%). Interestingly, 6 months post symptoms onset, the majority of the samples (N = 44/52, 84.6%) were still positive for NAbs. This is in sharp contrast with the results we obtained 6 months post-vaccination in our cohort of healthcare workers who have received the two-dose regimens of BNT162b2. In this cohort of vaccinated subjects, 43% (n = 25/58) of the participants no longer exhibit NAbs activity 180 days after the administration of the first dose of BNT162b2.

International Journal of Laboratory HematologyVolume 43, Issue 1 p. e48-e51 LETTER TO THE EDITOR Are the DOAC plasma level thresholds appropriate for clinical decision-making? A reappraisal using thrombin generation testing Jonathan Evrard, Jonathan Evrard orcid.org/0000-0003-4255-1591 Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, BelgiumSearch for more papers by this authorMichaël Hardy, Michaël Hardy Department of Anesthesiology, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, Yvoir, Belgium Hematology Laboratory, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, Yvoir, BelgiumSearch for more papers by this authorJean-Michel Dogné, Jean-Michel Dogné Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium Namur Biobank-eXchange (NAB-X), University of Namur, Namur, BelgiumSearch for more papers by this authorSarah Lessire, Sarah Lessire Department of Anesthesiology, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, Yvoir, BelgiumSearch for more papers by this authorVincent Maloteau, Vincent Maloteau Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, BelgiumSearch for more papers by this authorFrançois Mullier, François Mullier orcid.org/0000-0001-6947-6099 Hematology Laboratory, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, Yvoir, BelgiumSearch for more papers by this authorJonathan Douxfils, Corresponding Author Jonathan Douxfils jonathan.douxfils@unamur.be orcid.org/0000-0002-7644-5298 Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium Qualiblood s.a, Namur, Belgium Correspondence Jonathan Douxfils, University of Namur, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Namur (5000), Belgium. Email: jonathan.douxfils@unamur.beSearch for more papers by this author Jonathan Evrard, Jonathan Evrard orcid.org/0000-0003-4255-1591 Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, BelgiumSearch for more papers by this authorMichaël Hardy, Michaël Hardy Department of Anesthesiology, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, Yvoir, Belgium Hematology Laboratory, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, Yvoir, BelgiumSearch for more papers by this authorJean-Michel Dogné, Jean-Michel Dogné Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium Namur Biobank-eXchange (NAB-X), University of Namur, Namur, BelgiumSearch for more papers by this authorSarah Lessire, Sarah Lessire Department of Anesthesiology, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, Yvoir, BelgiumSearch for more papers by this authorVincent Maloteau, Vincent Maloteau Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, BelgiumSearch for more papers by this authorFrançois Mullier, François Mullier orcid.org/0000-0001-6947-6099 Hematology Laboratory, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, Yvoir, BelgiumSearch for more papers by this authorJonathan Douxfils, Corresponding Author Jonathan Douxfils jonathan.douxfils@unamur.be orcid.org/0000-0002-7644-5298 Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium Qualiblood s.a, Namur, Belgium Correspondence Jonathan Douxfils, University of Namur, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Namur (5000), Belgium. Email: jonathan.douxfils@unamur.beSearch for more papers by this author First published: 10 October 2020 https://doi.org/10.1111/ijlh.13356Citations: 8Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume43, Issue1February 2021Pages e48-e51 RelatedInformation