Evaluation of the correlation between the access SARS-CoV-2 IgM and IgG II antibody tests with the SARS-CoV-2 surrogate virus neutralization test.

Fully automated immunoassays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies that are strongly correlated with neutralization antibodies (nAbs) are clinically important because they enable the assessment of humoral immunity after infection and vaccination. Access SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) II antibody tests are semi-quantitative, fully automated immunoassays that detect anti-receptor-binding domain (RBD) antibodies and might reflect nAb levels in coronavirus disease 2019 (COVID-19). However, no studies have investigated the clinical utility of these tests in association with nAbs to date. To evaluate the clinical utility of Access SARS-CoV-2 IgM and IgG II antibody tests and their correlation with the SARS-CoV-2 surrogate virus neutralization test (sVNT) that measures nAbs in patients with COVID-19, we analyzed 54 convalescent serum samples from COVID-19 patients and 89 serum samples from non-COVID-19 patients. The presence of anti-RBD antibodies was detected using Access SARS-CoV-2 IgM and IgG II antibody tests, while nAbs were measured by sVNT. The sensitivity and specificity of sVNT were 94.4% and 98.9%, respectively. There were strong positive correlations between the inhibition values of sVNT and the results of the Access SARS-CoV-2 IgM (R = 0.95, R2 = 0.90, p < 0.001) and IgG II antibody tests (R = 0.96, R2 = 0.92, p < 0.001). In terms of the presence of nAbs, the sensitivity and specificity were 98.1% and 98.9% in the IgM assay and 100.0% and 100.0% in the IgG II assay, respectively. The Access SARS-CoV-2 IgM and IgG II antibody tests showed high sensitivity and specificity for the detection of nAbs in COVID-19 patients and might be alternatives for measuring nAbs.

Cross-reactive humoral immune responses against seasonal human coronaviruses in COVID-19 patients with different disease severities.

BACKGROUND: The cross-reactive antibody response against seasonal human coronaviruses (HCoVs) was evaluated according to disease severity in patients with COVID-19 in Japan. METHODS: In total, 194 paired serum samples collected from 97 patients with COVID-19 (mild, 35; severe, 62) were analyzed on admission and during convalescence. IgG antibodies against the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2 and four seasonal HCoVs (HCoV-NL63, -229E, -OC43, and -HKU1) were detected by enzyme-linked immunosorbent assays. RESULTS: There was no difference in optical density (OD) values for seasonal HCoVs on admission between the severe and mild cases. In addition, a specific pattern of disease severity-associated OD values for HCoVs was not identified. Significant increases in OD values from admission to convalescence for HCoV-HKU1and -OC43 IgG-S, and for HCoV-NL63 and -229E IgG-N were observed in the severe cases. Significant differences were observed between the mild and severe cases for HCoV-HKU1 and -OC43 IgG-S OD values during convalescence. Correlations were found between the fold changes for HCoV-OC43 IgG-S OD values, and for SARS-CoV-2 IgG-S OD values, and C-reactive protein, lactate dehydrogenase, and lymphocyte levels. CONCLUSION: There was no association between the antibody titer for seasonal HCoVs in the early phase of COVID-19 and disease severity.

Clinical characteristics and antibody response to SARS-CoV-2 spike 1 protein using VITROS Anti-SARS-CoV-2 antibody tests in COVID-19 patients in Japan.

Introduction. Serological tests for COVID-19 are important in providing results for surveillance and supporting diagnosis. Investigating the serological response in COVID-19 patients with different disease severity is important for assessing the clinical utility of serological assays.Gap Statement. However, few studies have investigated the clinical utility of antibody assays for COVID-19 or differences in antibody response in association with disease severity.Aim. The study aimed to evaluate the clinical characteristics and clinical utility of VITROS SARS-CoV-2 antibody tests according to COVID-19 severity in patients in Japan.Methodology. We analysed 255 serum specimens from 130 COVID-19 patients and examined clinical records and laboratory data. Presence of total (IgA, IgM, and IgG) and specific IgG antibody for the spike 1 antigen of SARS-CoV-2 was determined using VITROS Anti-SARS-CoV-2 antibody tests.Results. Overall, 98 (75.4 %) and 32 (24.6 %) patients had mild and severe COVID-19, respectively. On admission, 76 (58.5 %) and 45 (34.6 %) patients were positive for total and IgG antibody assays. Among 91 patients at discharge, 90 (98.9 %) and 81 (89.0 %) were positive for total and IgG antibody, respectively. Clinical background and laboratory findings on admission, but not the prevalence or concentration of total or IgG antibody, were associated with disease prognosis. Total and IgG antibody intensities were significantly higher in severe cases than in mild cases in serum collected >11 days after onset, but not within 10 days.Conclusion. VITROS Anti-SARS-CoV-2 total and IgG assays will be useful as supporting diagnostic and surveillance tools and for evaluation of humoral immune response to COVID-19. Optimal prediction of disease prognosis is made from considering both clinical history and laboratory findings.

Clinical evaluation of the antibody response in patients with COVID-19 using automated high-throughput immunoassays.

Several automated high-throughput immunoassays for detecting anti-SARS-CoV-2 antibodies by a semi-quantitative approach have been commercialized. In this study, we describe the timeline of the antibody response in patients with RT-PCR-confirmed COVID-19. A total of 292 sequential serum samples from 33 Japanese patients were retrospectively analyzed using four test kits for SARS-CoV-2: the Abbott SARS-CoV-2 IgG assay (Abbott), Elecsys® Anti-SARS-CoV-2 assay (Roche Diagnostic), and VITROS® Anti-SARS-CoV-2 Total and IgG assays (Ortho Clinical Diagnostics). All automated immunoassays could equivalently identify positive sera collected within 2 weeks after symptom onset (99.3%-100%). In addition, the S protein-based automated immunoassay, the VITROS® Anti-SARS-CoV-2 Total assay, may play a complementary role in evaluating passive antibody therapies or vaccines against SARS-CoV-2, although further research is required.

Antibody response patterns in COVID-19 patients with different levels of disease severity in Japan.

We analyzed antibody response patterns according to the level of disease severity in patients with novel coronavirus disease 2019 (COVID-19) in Japan. We analyzed 611 serum specimens from 231 patients with COVID-19 (mild, 170; severe, 31; critical, 30). Immunoglobulin M (IgM) and IgG antibodies against nucleocapsid protein (N) and spike 1 protein (S1) were detected by enzyme-linked immunosorbent assays. The peaks of fitting curves for the optical density (OD) values of IgM and IgG antibodies against N appeared simultaneously, while those against S1 were delayed compared with N. The OD values of IgM against N and IgG against both N and S1 were significantly higher in the severe and critical cases than in the mild cases at 11 days after symptom onset. The seroconversion rates of IgG were higher than those of IgM against both N and S1 during the clinical course based on the optimal cut-off values defined in this study. The seroconversion rates of IgG and IgM against N and S1 were higher in the severe and critical cases than in the mild cases. Our findings show that a stronger antibody response occurred in COVID-19 patients with greater disease severity and there were low seroconversion rates of antibodies against N and S1 in the mild cases.

A preliminary study on pre-operative tumor volumetry measured by three-dimensional computer tomography in gastric cancer.

BACKGROUND/AIMS: The aim of the present study was to evaluate the clinical significance of tumor volumetry measured by three-dimensional (3-D) multidetector row computed tomography (MD-CT). METHODOLOGY: A total of 50 patients with gastric cancer who had undergone pre-operative tumor volumetry using 3D-MD-CT followed by subsequent laparotomy (11 women, 39 men; mean age 63.9 years) were examined. Tumor volume and conventional clinicopathological factors were studied and then analyzed with respect to survival. RESULTS: Tumor volume was distributed widely and ranged from 0.16 cm3 to 363.5 cm3 with a mean of 43.6 cm3 (<10 cm3, 21 tumors; ≥10 cm3, 29 tu- mors). Significant differences in survival were found for volume (<10.0 cm3 vs. ≥10.0 cm3; p=0.0414), and depth of invasion (T1-2 vs. T3-4; p=0.0475), but not for diameter (<50 mm vs. ≥50 mm; p=0.2142), location (proximal third vs. middle or distal third; p=0.3254), macroscopic type (localized vs. invasive; p=0.3619), or microscopic type (differentiated vs. undifferentiated; p=0.1230). CONCLUSIONS: The present findings suggest that tumor volume measured by pre-operative 3D-MD-CT offers an alternative indicator for determining the prognosis in gastric cancer.

Synthesis and structure-activity relationship of tricyclic carboxylic acids as novel anti-histamines.

A series of tricyclic carboxylic acids having 6-amino-pyrimidine-2,4(1H,3H)-dione with piperazino or homopiperazino moiety linked by propylene, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice, bioavailability in rats, and their anti-inflammatory activity in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, dibenzoxazepine carboxylic acid 13b showed both histamine H(1) receptor antagonistic activity and anti-inflammatory activity in vivo. In addition, 13b exhibited low affinity toward α(1) receptor and low occupancy of H(1) receptor in the brain. It is therefore, believed that 13b is a potential candidate for development as 3rd generation anti-histamine.

Synthesis and structure-activity relationships of phenothiazine carboxylic acids having pyrimidine-dione as novel histamine H(1) antagonists.

A series of phenothiazine carboxylic acid derivatives, having 6-amino-pyrimidine-2,4(1H,3H)-dione moiety via a appropriate linker, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice and bioavailability in rats. Finally, promising compounds were examined for their anti-inflammatory potential in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, phenothiazineacetic acid compound 27 showed both histamine H(1)-receptor antagonistic activity and anti-inflammatory activity in vivo model.

Pre-operative tumor assessment of patients with gastric cancer based on virtual endoscopy using multidetector-row computer tomography.

BACKGROUND: The possibilities and limitations of computer tomography (CT) examination for detecting primary gastric cancer tumors have been poorly understood. The aim of the present study was to evaluate the pre-operative assessment of gastric cancer tumors using 32-multidetector row-CT. PATIENTS AND METHODS: A prospective study of the pre-operative assessment of gastric cancer tumors using 32-multidetector row-CT was carried out. Seventy-four patients with adenocarcinoma of the stomach (T1 tumors, 38; T2 and T3 tumors, 36) underwent abdominal CTs to assess the feasibility of using MD-CT to assess primary lesions. RESULTS: In 35 (47%) out of the 74 patients, the primary lesions could be detected on 2-D images obtained by CT. In these patients, virtual endoscopic images of these tumors could be created. Twenty-seven advanced cancer tumors (75%) were assessed based on 2-D CT images and 27 larger tumors (>40 mm) (69%) were assessed based on 2-D CT images. Significant differences were found with respect to depth of tumor (p<0.0001) and tumor size (p<0.0001) between tumors that could or could not be assessed on MD-CT. CONCLUSION: The findings of the present study show that CT assessment of tumors is feasible in patients with advanced gastric cancer. Future studies are required to fully explore the ability of MD-CT to assess tumor volume in advanced gastric cancer cases and to determine the optimum application of this approach.

New diagnostic imaging of gastointestinal tumors: a preliminary study of three-dimensional tumor structure and volumetry.

BACKGROUND: The aim of the present report was to present preliminary results of the pre-operative evaluation of three-dimensional tumor structure and volumetry using three-dimensional computed tomography (3-D CT) and three-dimensional endoscopic ultrasonography (3-D EUS). MATERIALS AND METHODS: Diagnostic imaging was performed for 2 patients (one with gastric cancer, one with a rectal tumor) using virtual endoscopy, 3-D CT for the patient with gastric cancer and 3-D EUS for the patient with the rectal tumor, for the pre-operative evaluation of tumor structure and volumetry. Computer-generated image analysis of resected tumors was also performed. RESULTS: The gastric tumor was successfully visualized using 3-D CT and the rectal tumor was successfully visualized using 3-D EUS. The values obtained for volume of the stomach tumor, calculated using 3-D CT and resected materials, were 15.1 cm3 and 11.4 cm3, respectively. The values obtained for volume of the rectal tumor, calculated using 3-D EUS and resected materials, were 2.3 cm3 and 3.9 cm3, respectively. CONCLUSION: The present findings demonstrate that clinically useful results can be obtained by using 3-D CT and 3-D EUS for the pre-operative evaluation of 3-D tumor structure and volumetry of gastrointestinal tumors. We expect that further studies of these methods will lead to the establishment of new diagnostic criteria for gastrointestinal tumors based on tumor volume in the near future.

[Usefulness of the FRFSE method in SPIO-MRI].

AIM: Super-paramagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) is highly sensitive for liver tumors. This trial examined the optimal parameters of the fast recovery fast spin echo (FRFSE) method in SPIO-MRI. The FRFSE method is a pulse sequence with recovery of the compulsory longitudinal magnetization. The FRFSE method used in SPIO-MRI has better sensitivity for liver tumor, better tumor contrast, and can be used with respiratory gating. MATERIALS AND METHODS: The phantoms used included a ferucarbotran phantom, water phantom, and gelatin phantom. Each phantom was scanned by the FRFSE method and fast spin echo (FSE) method, with changing of scanning parameters, and each CNR was measured. Each CNR was given a point, and points were averaged according to each parameter. Parameters that obtained high average points were considered optimal parameters. RESULTS: The optimal parameters were set to TE=50 ms in the FRFSE method. The scan parameters optimized from the phantom study were used in a clinical case, and good results were achieved, as in the phantom study. CONCLUSION: We optimized the scan parameters of the FRFSE method and were able to suggest the usefulness of the FRFSE method in SPIO-MRI.

New anti-MRSA and anti-VRE carbapenems; synthesis and structure-activity relationships of 1beta-methyl-2-(thiazol-2-ylthio)carbapenems.

Discovery of novel antimicrobial agents effective against infections caused by drug-resistant pathogens is an important objective. In order to find a new parenteral carbapenem antibiotic, which has potent antibacterial activity especially against methicillin-resistant staphylococci, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae, a series of 1beta-methylcarbapenems with thiazol-2-ylthio groups at the C-2 position have been synthesized. Structure-activity relationships were investigated which led to SM-197436 (27), SM-232721 (44) and SM-232724 (41), being selected for further evaluation.

Strained silacycles in organic synthesis: a new reagent for the enantioselective allylation of aldehydes.

A new reagent for the enantioselective allylation of aliphatic aldehydes has been developed. The reagent is easily prepared in a single step from commercially available materials and may be stored without significant decomposition. The reactivity of the reagent is attributed to strain-release Lewis acidity.