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Open accessPosted ContentDOI: 10.1101/2021.03.02.21252203

Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay

02 Mar 2021-medRxiv (Cold Spring Harbor Laboratory Press)-
Abstract: Background The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the in vitro quantitative detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the performance of this assay using samples from seven sites in Germany, Austria, and Switzerland. Methods Anonymized frozen, residual serum, or plasma samples from blood donation centers or routine diagnostic testing were used for this study. For specificity and sensitivity analyses, presumed negative samples collected before October 2019 and SARS-CoV-2 PCR-confirmed single or sequential samples were tested, respectively. The performance of the Elecsys Anti-SARS-CoV-2 S immunoassay was also compared with other commercial immunoassays. Results The overall specificity (n=7880 pre-pandemic samples) and sensitivity (n=240 PCR-positive samples [≥14 days post-PCR]) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87–99.99) and 97.92% (95% CI: 95.21– 99.32), respectively. Compared with seven other immunoassays, the Elecsys Anti-SARS-CoV-2 S assay had comparable or greater specificity and sensitivity. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON® SARS-CoV-2 S1/S2 IgG, ADVIA Centaur® SARS-CoV-2 Total, ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG and IgA assays, and significantly higher sensitivity (≥14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgG and IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG assays. Conclusion The Elecsys Anti-SARS-CoV-2 S assay demonstrated a robust and favorable performance across samples from multiple European sites, with a very high specificity and sensitivity for the detection of anti-S antibodies.

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Topics: Immunoassay (51%)
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11 results found


Open accessJournal ArticleDOI: 10.3390/DIAGNOSTICS11050832
04 May 2021-
Abstract: Background: This study monitored total anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) RBD (receptor-binding domain) antibodies levels in a large population of healthcare workers undergoing mRNA COVID-19 vaccination. Methods. The study population consisted of employees of Pederzoli Hospital of Peschiera del Garda (Verona, Italy), who underwent voluntary vaccination with two doses of COVID-19 mRNA BNT162b2 (Comirnaty; Pfizer Inc). Venous blood was drawn immediately before the first vaccine dose, as well as 21 days (immediately before second vaccine dose) and 50 days afterwards. Humoral response was assessed with Roche Elecsys Anti-SARS-CoV-2 S total antibodies, on Roche Cobas 6000 (Roche Diagnostics). Results: The final study population consisted of 925 subjects (mean age, 44 ± 13 years; 457 women), 206 (22.3%) anti-SARS-CoV-2 baseline seropositive. The increase of total anti-SARS-CoV-2 RBD antibodies levels 21 days after the first vaccine dose was ~3 orders of magnitude higher in seropositive than in seronegative individuals (11782 vs. 42 U/mL; p < 0.001). Total anti-SARS-CoV-2 RBD antibodies levels further increased by over 30-fold after the second vaccine dose in baseline seronegative subjects, while such increase was only ~1.3-fold in baseline seropositive subjects. In multivariate analysis, total anti-SARS-CoV-2 RBD antibodies level was inversely associated with age after both vaccine doses and male sex after the second vaccine dose in baseline seronegative subjects, while baseline antibodies value significantly predicted immune response after both vaccine doses in baseline seropositive recipients. Conclusion: Significant difference exists in post-mRNA COVID-19 vaccine immune response in baseline seronegative and seropositive subjects, which seems dependent on age and sex in seronegative subjects, as well as on baseline anti-SARS-CoV-2 antibodies level in seropositive patients.

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Topics: Vaccination (52%), Population study (50%)

22 Citations


Open accessJournal ArticleDOI: 10.1007/S00296-021-04910-7
Abstract: To assess antibody response to inactivated COVID-19 vaccine in patients with immune-mediated diseases (IMD) among hospital workers and people aged 65 and older. In this cross-sectional study, we studied 82 hospital workers with IMD (mean age: 42.2 ± 10.0 years) and 300 (mean age: 41.7 ± 9.9 years) controls. Among + 65 aged population, we studied 22 (mean age: 71.4 ± 4.5 years) patients and 47 controls (mean age: 70.9 ± 4.8 years). All study subjects had a negative history for COVID-19. Sera were obtained after at least 21 days following the second vaccination. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. Patients with IMD were significantly less likely to have detectable antibodies than healthy controls both among the hospital workers (92.7% vs 99.7%, p < 0.001) and elderly population (77.3% vs 97.9%, p = 0.011). Among patients with IMD, those using immunosuppressive or immune-modulating drugs (64/75, 85.3%) were significantly less likely to have detectable antibodies compared to those off treatment (29/29, 100%) (p = 0.029). Additionally, a negative association between age and the antibody titer categories among patients (r = − 0.352; p < 0.001) and controls (r = − 0.258; p < 0.001) were demonstrated. Among hospital workers, the vast majority of patients with IMD and immunocompetent controls developed a significant humoral response following the administration of the second dose of inactivated COVID-19 vaccine. This was also true for the elderly population, albeit with lower antibody titers. Immunosuppressive use, particularly rituximab significantly reduced antibody titers. Antibody titers were significantly lower among those aged ≥ 60 years both in patient and control populations. Whether these individuals should get a booster dose warrants further studies.

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Topics: Antibody titer (57%), Booster dose (51%)

15 Citations


Open accessPosted ContentDOI: 10.1101/2021.05.12.21257102
15 May 2021-medRxiv
Abstract: Background Vaccination constitutes the best long-term solution against Coronavirus Disease 2019 (COVID-19). Real-world immunogenicity data are sparse, particularly for ChAdOx1 and in populations with chronic conditions; and given the UK’s extended dosing interval, it is also important to understand antibody responses in SARS-CoV-2-naive individuals following a single dose. Methods Adults aged ≥18 years from households enrolled in Virus Watch, a prospective community cohort study in England and Wales, provided capillary blood samples and self-reported vaccination status. Primary outcome variables were quantitative Spike total antibody levels (U/ml) and seropositivity to Spike (≥0.8 U/ml), as per Roche’s Elecsys Anti-SARS-CoV-2 S assay. Samples seropositive for Nucleocapsid, and samples taken prior to vaccination, were excluded. Outcomes were analysed by days since vaccination, vaccine type (BNT162b2 and ChAdOx1), and a range of self-reported demographic and clinical factors. Results 8,837 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 17,160 samples (10,508 following ChAdOx1, 6,547 following BNT162b2). Seropositivity to Spike was 96.79% (95% CI 96.42, 97.12) from 28 days following a single dose, reaching 99.34% (98.91, 99.60) from 14 days after a second dose. Seropositivity rates, and Spike-antibody levels rose more quickly following the first dose of BNT162b2, however, were equivalent for both vaccines by 4 and 8 weeks, respectively. There was evidence for lower S-antibody levels with increasing age (p=0.0001). In partially vaccinated 65-79 year-olds, lower S-antibody levels were observed in men compared with women (26.50 vs 44.01 U/ml, p Interpretation A single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. Observed disparities in antibody levels by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures for partially vaccinated adults, particularly those who are older and more clinically vulnerable; and high antibody levels across all groups following a second dose demonstrate the importance of complete vaccination. However, the relationship between Spike-antibody levels and protection against COVID-19, and thus the clinical significance of observed disparities, is not yet clear.

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Topics: Vaccination (51%)

15 Citations


Open accessJournal ArticleDOI: 10.1182/BLOODADVANCES.2021005094
Chava Perry1, Chava Perry2, Efrat Luttwak2, Efrat Luttwak1  +22 moreInstitutions (2)
24 Aug 2021-Blood Advances
Abstract: Patients diagnosed with B-cell non-Hodgkin lymphoma (B-NHL), particularly if recently treated with anti-CD20 antibodies, are at risk of severe COVID-19 disease. Because studies evaluating humoral response to COVID-19 vaccine in these patients are lacking, recommendations regarding vaccination strategy remain unclear. The humoral immune response to BNT162b2 messenger RNA (mRNA) COVID-19 vaccine was evaluated in patients with B-NHL who received 2 vaccine doses 21 days apart and compared with the response in healthy controls. Antibody titer, measured by the Elecsys Anti-SARS-CoV-2S assay, was evaluated 2 to 3 weeks after the second vaccine dose. Patients with B-NHL (n = 149), aggressive B-NHL (a-B-NHL; 47%), or indolent B-NHL (i-B-NHL; 53%) were evaluated. Twenty-eight (19%) were treatment naive, 37% were actively treated with a rituximab/obinutuzumab (R/Obi)-based induction regimen or R/Obi maintenance, and 44% had last been treated with R/Obi >6 months before vaccination. A seropositive response was achieved in 89%, 7.3%, and 66.7%, respectively, with response rates of 49% in patients with B-NHL vs 98.5% in 65 healthy controls (P < .001). Multivariate analysis revealed that longer time since exposure to R/Obi and absolute lymphocyte count ≥0.9 × 103/μL predicted a positive serological response. Median time to achieve positive serology among anti-CD20 antibody-treated patients was longer in i-B-NHL vs a-B-NHL. The humoral response to BNT162b2 mRNA COVID-19 vaccine is impaired in patients with B-NHL who are undergoing R/Obi treatment. Longer time since exposure to R/Obi is associated with improved response rates to the COVID-19 vaccine. This study is registered at www.clinicaltrials.gov as #NCT04746092.

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Topics: Vaccination (52%)

12 Citations


Open accessJournal ArticleDOI: 10.3390/PHARMACEUTICS13060874
13 Jun 2021-Pharmaceutics
Abstract: The widespread use of antibiotics has resulted in the emergence of drug-resistant populations of microorganisms. Clearly, one can see the need to develop new, more effective, antimicrobial agents that go beyond the explored 'chemical space'. In this regard, their unique modes of action (e.g., reactive oxygen species (ROS) generation, redox activation, ligand exchange, depletion of substrates involved in vital cellular processes) render metal complexes as promising drug candidates. Several Ru (II/III) complexes have been included in, or are currently undergoing, clinical trials as anticancer agents. Based on the in-depth knowledge of their chemical properties and biological behavior, the interest in developing new ruthenium compounds as antibiotic, antifungal, antiparasitic, or antiviral drugs has risen. This review will discuss the advantages and disadvantages of Ru (II/III) frameworks as antimicrobial agents. Some aspects regarding the relationship between their chemical structure and mechanism of action, cellular localization, and/or metabolism of the ruthenium complexes in bacterial and eukaryotic cells are discussed as well. Regarding the antiviral activity, in light of current events related to the Covid-19 pandemic, the Ru (II/III) compounds used against SARS-CoV-2 (e.g., BOLD-100) are also reviewed herein.

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Topics: Cellular localization (57%)

5 Citations


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37 results found


Open accessJournal Article
01 Jan 2014-MSOR connections
Abstract: Copyright (©) 1999–2012 R Foundation for Statistical Computing. Permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and this permission notice are preserved on all copies. Permission is granted to copy and distribute modified versions of this manual under the conditions for verbatim copying, provided that the entire resulting derived work is distributed under the terms of a permission notice identical to this one. Permission is granted to copy and distribute translations of this manual into another language, under the above conditions for modified versions, except that this permission notice may be stated in a translation approved by the R Core Team.

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Topics: R Programming Language (78%)

229,202 Citations


Open accessJournal ArticleDOI: 10.1038/S41586-020-2008-3
Fan Wu1, Su Zhao2, Bin Yu3, Yan-Mei Chen1  +17 moreInstitutions (4)
03 Feb 2020-Nature
Abstract: Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1–3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.

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Topics: Coronavirus (62%), Betacoronavirus (59%), Zika virus disease (54%) ... read more

6,266 Citations


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30154-9
Jasper Fuk-Woo Chan1, Shuofeng Yuan1, Kin-Hang Kok1, Kelvin K. W. To1  +19 moreInstitutions (2)
15 Feb 2020-The Lancet
Abstract: Summary Background An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. Methods In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. Findings From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6–10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Interpretation Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. Funding The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).

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Topics: Coronavirus (51%)

5,975 Citations


Open accessJournal ArticleDOI: 10.1126/SCIENCE.ABB2507
13 Mar 2020-Science
Abstract: The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

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5,197 Citations


Open accessJournal ArticleDOI: 10.1016/J.CELL.2020.02.058
16 Apr 2020-Cell
Abstract: The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

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Topics: Ectodomain (56%), Viral entry (55%), Epitope (53%) ... read more

4,968 Citations