Fatal case of subdural empyema caused by Campylobacter rectus and Slackia exigua.

We report a fatal subdural empyema caused by Campylobacter rectus in a 66-year-old female who developed acute onset of confusion, dysarthria, and paresis in her left extremities. A CT scan showed hypodensity in a crescentic formation with a mild mid-line shift. She had a bruise on her forehead caused by a fall several days before admission, which initially raised subdural hematoma (SDH) diagnosis, and a burr hole procedure was planned. However, her condition deteriorated on the admission night, and she died before dawn. An autopsy revealed that she had subdural empyema (SDE) caused by Campylobacter rectus and Slackia exigua. Both microorganisms are oral microorganisms that rarely cause extra-oral infection. In our case, head trauma caused a skull bone fracture, and sinus infection might have expanded to the subdural space causing SDE. CT/MRI findings were not typical for either SDH or SDE. Early recognition of subdural empyema and prompt initiation of treatment with antibiotics and surgical drainage is essential for cases of SDE. We present our case and a review of four reported cases.

Fatal case of subdural empyema caused by Campylobacter rectus and Slackia exigua

ABSTRACT We report a fatal subdural empyema caused by Campylobacter rectus in a 66-year-old female who developed acute onset of confusion, dysarthria, and paresis in her left extremities. A CT scan showed hypodensity in a crescentic formation with a mild mid-line shift. She had a bruise on her forehead caused by a fall several days before admission, which initially raised subdural hematoma (SDH) diagnosis, and a burr hole procedure was planned. However, her condition deteriorated on the admission night, and she died before dawn. An autopsy revealed that she had subdural empyema (SDE) caused by Campylobacter rectus and Slackia exigua. Both microorganisms are oral microorganisms that rarely cause extra-oral infection. In our case, head trauma caused a skull bone fracture, and sinus infection might have expanded to the subdural space causing SDE. CT/MRI findings were not typical for either SDH or SDE. Early recognition of subdural empyema and prompt initiation of treatment with antibiotics and surgical drainage is essential for cases of SDE. We present our case and a review of four reported cases.

Serum stratifin and presepsin as candidate biomarkers for early detection of COVID-19 disease progression.

The prognosis of patients with severe cases of COVID-19 is poor; thus, biomarkers for earlier prediction of COVID-19 progression are vital. We measured levels of five lung injury-related biomarkers, SP-D, KL-6, presepsin, kallistatin and stratifin, in serum samples collected serially during hospitalization from 31 patients with mild/moderate or severe/critical COVID-19 pneumonia, and their predictive performances were compared. Like the previously reported presepsin, a new biomarker candidate, stratifin, was significantly elevated with the onset of severe or critical symptoms in COVID-19 patients and decreased with symptom improvement. Notably, changes in stratifin and presepsin levels were distinctly earlier than those in SP-D, KL-6 and even SpO2/FiO2 values. Furthermore, serum levels of these biomarkers were significantly higher at the pre-severe stage (before the start of oxygen support) of patients who eventually advanced to severe/critical stages than in the patients who remained at the mild/moderate stage. These results were confirmed in an independent cohort, including 71 mild/moderate and 14 severe/critical patients, for whom the performance of stratifin and presepsin in discriminating between mild/moderate and pre-severe conditions of COVID-19 patients was superior to that of the SpO2/FiO2 ratio. Therefore, we concluded that stratifin and presepsin could be used as prognostic biomarkers for severe COVID-19 progression.

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.

Evaluation of a chemiluminescent enzyme immunoassay-based high-throughput SARS-CoV-2 antigen assay for the diagnosis of COVID-19: The VITROS® SARS-CoV-2 Antigen Test.

A high-throughput, fully automated antigen detection test for SARS-CoV-2 is a viable alternative to reverse-transcription polymerase chain reaction (RT-qPCR) for mass screening during outbreaks. In this study, we compared RT-qPCR for viral load and the VITROS® SARS-CoV-2 Antigen Test with reference to the results of the LUMIPULSE® SARS-CoV-2 Ag Test. Of 128 nasopharyngeal swab specimens taken from patients suspected of being infected with SARS-CoV-2, 49 were positive and 79 were negative according to RT-qPCR. Consistent dose-dependent detection with VITROS® assay was successfully achieved when using nasopharyngeal swab specimens with Ct values of 32.0 or lesser, whereas the CLEIA-based LUMIPULSE® assay was able to detect lower viral loads compared with the VITROS® assay. Our results show that the performance of the VITROS® assay was satisfactory for the diagnosis of contagious COVID-19 patients in the clinical setting. Highlights The performance of the VITROS® SARS-CoV-2 Antigen Test was sufficient for the diagnosis of contagious COVID-19. This test showed high sensitivity and specificity in the detection of SARS-CoV-2 in samples with a Ct value of 32 or less.

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.

Sequentially timed all-optical mapping photography boosted by a branched 4f system with a slicing mirror.

We present sequentially timed all-optical mapping photography (STAMP) with a slicing mirror in a branched 4f system for an increased number of frames without sacrificing pixel resolution. The branched 4f system spectrally separates the laser light path into multiple paths by the slicing mirror placed in the Fourier plane. Fabricated by an ultra-precision end milling process, the slicing mirror has 18 mirror facets of differing mirror angles. We used the boosted STAMP to observe dynamics of laser ablation with two image sensors which captured 18 subsequent frames at a frame rate of 126 billion frames per second, demonstrating this technique's potential for imaging unexplored ultrafast non-repetitive phenomena.

Evaluation of rapid diagnosis of novel coronavirus disease (COVID-19) using loop-mediated isothermal amplification.

With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for more rapid and simple detection technologies at the forefront of medical care worldwide. In this study, we evaluated the effectiveness of the Loopamp® 2019-SARSCoV-2 Detection Reagent Kit, which uses loop-mediated isothermal amplification (LAMP) technology. In this protocol, cDNA is synthesized from SARS-CoV-2 RNA using reverse transcriptase, followed by DNA amplification under isothermal conditions in one step. The RT-LAMP test kit amplified the targeted RNA of a SARS-CoV-2 isolate with a detection limit of 1.0 × 101 copies/µL, which was comparable to the detection sensitivity of quantitative reverse transcription PCR (RT-qPCR). Comparison with the results of RT-qPCR for 76 nasopharyngeal swab samples from patients with suspected COVID-19 showed a sensitivity of 100 % and a specificity of 97.6 %. In the 24 RNA specimens derived from febrile Japanese patients with or without influenza A, no amplification was observed using RT-LAMP. RT-LAMP could be a simple and easy-to-use diagnostic tool for the detection of SARS-CoV-2.

Clinical evaluation of an immunochromatographic IgM/IgG antibody assay and chest computed tomography for the diagnosis of COVID-19.

BACKGROUND: We evaluated the clinical performance of an immunochromatographic (IC) IgM/IgG antibody assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and chest computed tomography (CT) for the diagnosis of Coronavirus disease 2019 (COVID-19). METHODS: We examined 139 serum specimens collected from 112 patients with COVID-19 and 48 serum specimens collected from 48 non-COVID-19 patients. The presence of IgM/IgG antibody for SARS-COV2 was determined using the One Step Novel Coronavirus (COVID-19) IgM/IgG Antibody Test. Chest CT was performed in COVID-19 patients on admission. FINDINGS: Of the139 COVID-19 serum specimens, IgM was detected in 27.8 %, 48.0 %, and 95.8 % of the specimens collected within 1 week, 1-2 weeks, and >2 weeks after symptom onset and IgG was detected in 3.3 %, 8.0 %, and 62.5 %, respectively. Among the 48 non-COVID-19 serum specimens, 1 generated a false-positive result for IgM. Thirty-eight of the 112 COVID-19 patients were asymptomatic, of whom 15 were positive for IgM, and 74 were symptomatic, of whom 22 were positive for IgM and 7 were positive for IgG. The diagnostic sensitivity of CT scan alone and in combination with the IC assay was 57.9 % (22/38) and 68.4 % (26/38) for the asymptomatic patients and 74.3 % (55/74) and 82.4 % (61/74) for the symptomatic patients, respectively. CONCLUSION: The IC assay had low sensitivity during the early phase of infection, and thus IC assay alone is not recommended for initial diagnostic testing for COVID-19. If RT-qPCR is not available, the combination of chest CT and IC assay may be useful for diagnosing COVID-19.

Low-field magnetoelectric effect at room temperature.

The discoveries of gigantic ferroelectric polarization in BiFeO(3) (ref. 1) and ferroelectricity accompanied by a magnetic order in TbMnO(3) (ref. 2) have renewed interest in research on magnetoelectric multiferroics, materials in which magnetic and ferroelectric orders coexist, from both fundamental and technological points of view. Among several different types of magnetoelectric multiferroic, magnetically induced ferroelectrics in which ferroelectricity is induced by complex magnetic orders, such as spiral orders, exhibit giant magnetoelectric effects, remarkable changes in electric polarization in response to a magnetic field. Many magnetically induced ferroelectrics showing the magnetoelectric effects have been found in the past several years. From a practical point of view, however, their magnetoelectric effects are useless because they operate only far below room temperature (for example, 28 K in TbMnO(3) (ref. 2) and 230 K in CuO (ref. 11)). Furthermore, in most of them, the operating magnetic field is an order of tesla that is too high for practical applications. Here we report materials, Z-type hexaferrites, overcoming these problems on magnetically induced ferroelectrics. The best magnetoelectric properties were obtained for Sr(3)Co(2)Fe(24)O(41) ceramics sintered in oxygen, which exhibit a low-field magnetoelectric effect at room temperature. Our result represents an important step towards practical device applications using the magnetoelectric effects.