Cut-off Index Research Articles

Salivary testing of COVID-19: evaluation of serological testing following positive salivary results

BackgroundSalivary detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proposed as an alternative to nasopharyngeal or oropharyngeal swab testing. Our group previously published a study demonstrating that both testing methods identified SARS-CoV-2 using polymerase chain reaction (PCR)-based detection methodology. We therefore conducted a follow-up study using antibody testing to evaluate the accuracy of saliva versus swabs for COVID-19 detection and the durability of antibody response.MethodsVenous blood samples were collected from consenting participants and the presence of serum antibodies for SARS-CoV-2 was evaluated on a large, automated immunoassay platform by the Roche anti-SARS-CoV-2 qualitative assay (Roche Diagnostics, Laval Quebec). Individuals with a serum antibody cut-off index (COI) ≥ 1.0 were considered positive.ResultsIn asymptomatic and mildly symptomatic patients with a previously positive standard swab and/or saliva SARS-CoV-2 PCR-test, 42 demonstrated antibodies with 13 patients positive by swab alone, and 8 patients positive by saliva alone.ConclusionsDespite their status as ‘current standard’ for COVID-19 testing, these findings highlight limitations of PCR-based tests.

Mac-2 Binding Protein Glycosylation Isomer for Screening High-Risk Esophageal Varices in Liver Cirrhotic Patient

Background: Esophageal varices occur at middle to advanced stages of cirrhosis and are associated with increased mortality due to their potential for rupture and bleeding. The aim of this study is to examine the accuracy of a surrogate marker, Mac-2 binding protein glycosylation isomer (M2BPGi), for screening high-risk esophageal varices in cirrhotic patients. Methods: Ninety-four cirrhotic patients who underwent endoscopy screening at Cipto Mangunkusumo Hospital, Jakarta, Indonesia were included. Patients with a history of ligation, portal vein thrombosis, or hepatocellular carcinoma were excluded. All enrolled patients underwent ultrasonography, transient elastography, and laboratory tests. The HISCL-5000 Sysmex analyzer was used to measure M2BPGi levels. Results: Of these 94 patients, 27 had high-risk esophageal varices and 67 had non-high-risk esophageal varices. M2BPGi levels were higher in patients with high-risk esophageal varices compared with those with non-high-risk esophageal varices (cutoff index (COI) of 11.4 vs. 3.7, p < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of M2BPGi with a cutoff value of 5 COI was 92.6%, 70.1%, 55.6%, and 95.9%, respectively. Conclusions: M2BPGi could be used as a non-invasive surrogate marker for ruling out high-risk esophageal varices in cirrhotic patients. This method is cheap and non-invasive and could be used as a screening tool in resource-limited settings.

Sofosbuvir-based therapies associated with regression of liver fibrosis in patients with hepatitis C virus infection: A prospective observational study.

Oral direct-acting antiviral (DAA) treatment leads to >95% sustained virological response (SVR) and could be clinically useful in regression of liver fibrosis in chronic hepatitis C virus (HCV) infection. We evaluated if ledipasvir/sofosbuvir or sofosbuvir + ribavirin is associated with regression of fibrosis in HCV patients who achieved SVR.In this prospective cohort study performed at 3 sites in Japan, patients with genotype 1 and genotype 2 were given standard treatment of ledipasvir 90 mg/sofosbuvir 400 mg and sofosbuvir 400 mg + 200–1000 mg/day ribavirin, respectively, for 12 weeks. Liver fibrosis was assessed using Mac-2-binding protein glycosylation isomer (M2BPGi) and other fibrosis markers (platelet count, Fib-4 index, liver stiffness measurement [LSM]) in patients who achieved SVR.A total of 98.1% of (n = 101/103) patients in genotype 1 cohort and 100% (n = 16/16) in the genotype 2 cohort achieved SVR12. Based on per-protocol analysis, M2BPGi levels showed a significant decrease (–2.2 cut-off index [COI], P < .0001) at week 48 after treatment initiation. Forty-three patients showed a significant decrease in Fib-4 index (–1.2, P < .0001), and 44 patients showed improvement in LSM (–5.9 kPa, P < .0001).Achievement of SVR after antiviral therapy was associated with fibrosis regression. M2BPGi correlated well with LSM at week 48 after treatment initiation, supporting the sustainable benefit of HCV therapy.

Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab

ObjectiveAntitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients...

Persistence of antibody response to SARS-CoV-2 in a cohort of haemodialysis patients with COVID-19.

BackgroundHaemodialysis patients are extremely vulnerable to COVID-19. Their immune response after infection is unclear. We have found high seroconversion rates in this population with 95% developing antibodies. It is unclear if and how long these antibodies persist. Here we investigate this with serial antibody testing.MethodsWe identified haemodialysis patients who had confirmed SARS-CoV-2 between March-May 2020 and measured monthly antibodies (IgG/IgM) in those who survived. We used a semi-quantitative cut-off index (COI) to create a qualitative result and plotted optical density (OD) over time. We used linear regression to examine the slope, as well as noting peak OD and time to peak OD. We correlated these against baseline demographics, markers of illness severity, and comorbidities.Results122 patients were analysed. All remained antibody positive during follow-up; for a minimum of 148 days. 71% had a positive gradient indicating increasing antibody positivity over time. We found that age (p = 0.01), duration of PCR positivity (p = 0.06) and presence of symptoms (p = 0.05) were associated with a longer time to peak OD. Immunosuppression did not alter peak OD but did lead to a non-significant increase in time to peak OD and more patients had a subsequent fall in Ab levels (p = 0.02). Diabetic patients were more likely to have a positive slope (OR 2.26).ConclusionsThese results indicate that haemodialysis patients have a robust and sustained antibody response after confirmed COVID-19 infection with no suggestion that immunosuppression weakens this response. Although unclear what protection these antibodies confer, this encouraging that haemodialysis patients should respond to vaccination.

Need for Confirmatory Neutralization Tests for Hepatitis B Surface Antigen Tests in Populations with Intermediate Prevalence.

Hepatitis B surface antigen (HBsAg) is known as the hallmark of hepatitis B virus (HBV) infection. This study aimed to determine whether an HBsAg neutralization test is necessary to accurately interpret HBsAg test results. Initially reactive HBsAg specimens from a 5-year period, with cutoff index values between 1.0 and 2.0, were subjected to neutralization confirmatory testing using an Elecsys HBsAg Confirmatory test kit (Roche Diagnostics GmbH. Mannheim, Germany). The neutralization test showed 46.1% positive (confirmed positive group) and 53.9% negative (confirmed negative group) results from the total specimens. Among the confirmed negative group, 79.5% of patients were confirmed to be negative for the current infection, whereas 4 patients in the chronic hepatitis B subgroup showed a neutralization percentage close to 40%. More than half of patients in the confirmed positive group were considered to be in the hepatitis B e antigen-negative inactive HBsAg carrier phase. In populations with intermediate HBV prevalence, a neutralization test is necessary to confirm an HBsAg result and reduce the false positive and false negative rates of initial HBsAg tests.

Specificity testing by point prevalence as a simple assessment strategy using the Roche Elecsys® anti-SARS-CoV-2 immunoassay

BackgroundThe detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mandatory for the diagnosis, retrospective assessment of disease progression, and correct evaluation of the current infection situation in the population. Many such assays have been launched by various manufacturers. Unfortunately, the new US Food and Drug Administration emergency use regulations have resulted in a situation where laboratories have to perform their own validation studies but many of these laboratories do not have the biobank needed to conduct the studies. MethodsWe introduce a method that allows institutions to quickly perform a verification study in a low-prevalence infection situation. As proof of concept, we used the Roche Elecsys® anti-SARS-CoV-2 electrochemiluminescence immunoassay and an SAP-based hospital information system. The Shenzhen YHLO Biotech IgM and IgG assay targeting other surface patterns was used as a confirmatory test. ResultsThe Roche assay demonstrated a limit of detection of 0.069 cutoff index and successfully passed the performance validation according to Clinical and Laboratory Standards Institute EP15-A3. The study population of 627 inpatients has a median age of 64 years, and approximately 13% of the group were under intensive care at the respective time point. All patients included tested negative for SARS-CoV-2 infection by quantitative reverse transcription polymerase chain reaction (cobas® 6800, Roche, Mannheim, Germany). Only one false-positive result was obtained, resulting in a specificity for the Roche Elecsys anti-SARS-CoV-2 test of 99.84% and a negative predictive value of 99.98%. ConclusionsThe anonymized use of residual material enables quick evaluation of anti-SARS-CoV-2 immunoassays, as shown in this work with the Roche Elecsys assay. Comparison of the control population with economic data makes it possible to validate the sampling set and therefore to determine diagnostic specificity. By use of the approach chosen, it was shown that the Roche test achieved very good results in terms of diagnostic specificity, reproducibility, and limit of detection.

Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma.

Background: This study assesses the feasibility of producing hyperimmune anti-COVID-19 intravenously administrable immunoglobulin (C-IVIG) from pooled convalescent plasma (PCP) to provide a safe and effective passive immunization treatment option for COVID-19. Materials & methods: PCP was fractionated by modified caprylic acid precipitation followed by ultrafiltration/diafiltration to produce hyperimmune C-IVIG. Results: In C-IVIG, the mean SARS-CoV-2 antibody level was found to be threefold (104 ± 30 cut-off index) that of the PCP (36 ± 8.5 cut-off index) and mean protein concentration was found to be 46 ± 3.7 g/l, comprised of 89.5% immunoglobulins. Conclusion: The current method of producing C-IVIG is feasible as it uses locally available PCP and simpler technology and yields a high titer of SARS-CoV-2 antibody. The safety and efficacy of C-IVIG will be evaluated in a registered clinical trial (NCT 04521309).

Serological Evaluation of Patients with Coronavirus Disease-2019 in Daegu, South Korea

Background: Early and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to prevent spread of the infection. Understanding of the antibody response to SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19) is insufficient, particularly in relation to those whose responses persist for more than 1 month after the onset of symptoms. We conducted a SARS-CoV-2 antibody test to identify factors affecting the serological response and to evaluate its diagnostic utility in patients with COVID-19.Methods: We collected 1,048 residual serum samples from 396 patients with COVID-19 confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2. The samples had been used for routine admission tests in six healthcare institutions in Daegu. Antibody to SARS-CoV-2 was analyzed and the cutoff index (COI) was calculated for quantitative analysis. The patients’ information was reviewed to evaluate the relationship between antibody positivity and clinical characteristics.Findings: The anti-SARS-CoV-2 antibody positivity rate was 85% and the average COI was 24·3. The positivity rate and COI increased with time elapsed since symptom onset. Anti-SARS-CoV-2 antibody persisted for at least 13 weeks after symptom onset at a high COI. There was a significant difference in anti-SARS-CoV-2 antibody positivity rate between patients with and without symptoms, but not according to sex or disease course. The descending COI pattern at weeks 1 to 5 after symptom onset was significantly more frequent in patients who died than in those who recovered. There was a correlation between anti-SARS-CoV-2 antibody positivity and the cycle threshold value of RdRP by real-time RT-PCR.Interpretation: Anti-SARS-CoV-2 antibody persisted for at least 13 weeks at a high COI in patients with COVID-19. A decreasing COI pattern up to fifth week may be associated with a poor prognosis of COVID-19. As new treatments and vaccines are introduced, it is important to monitor continuously the usefulness of anti-SARS-CoV-2 antibody assays.Funding Statement: Research Program funded by the Korea Centers for Disease Control and Prevention (2020ER551000).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study protocol was reviewed and approved by the Institutional Review Board of Medicity Daegu Joint (approval no. DGIRB 2020-05-009-003).

Evaluation of four commercial, fully automated SARS-CoV-2 antibody tests suggests a revision of the Siemens SARS-CoV-2 IgG assay.

Serological tests detect antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the ongoing coronavirus disease-19 (COVID-19) pandemic. Independent external clinical validation of performance characteristics is of paramount importance. Four fully automated assays, Roche Elecsys Anti-SARS-CoV-2, Abbott SARS-CoV-2 IgG, Siemens SARS-CoV-2 total (COV2T) and SARS-CoV-2 IgG (COV2G) were evaluated using 350 pre-pandemic samples and 700 samples from 245 COVID-19 patients (158 hospitalized, 87 outpatients). All tests showed very high diagnostic specificity. Sensitivities in samples collected at least 14days after disease onset were slightly lower than manufacturers' claims for Roche (93.0%), Abbott (90.8%), and Siemens COV2T (90.3%), and distinctly lower for Siemens COV2G (78.8%). Concordantly negative results were enriched for immunocompromised patients. ROC curve analyses suggest a lowering of the cut-off index for the Siemens COV2G assay. Finally, the combination of two anti-SARS-CoV-2 antibody assays is feasible when considering borderline reactive results. Thorough on-site evaluation of commercially available serologic tests for detection of antibodies against SARS-CoV-2 remains imperative for laboratories. The potentially impaired sensitivity of the Siemens COV2G necessitates a switch to the company's newly filed SARS-CoV-2 IgG assay for follow-up studies. A combination of tests could be considered in clinical practice.

Possible correlation of electrochemiluminescence based numerical cut off index value with concentration of anti-SARS-CoV-2 antibody: Is it worth reporting?

Background: Many laboratories are reporting a numerical cutoff index value (COI) value for most anti-SARS-CoV-2 qualitative tests. These numerical values in patients’ report ultimately created great confusion in the public and physicians, therefore this study was designed to evaluate the correlation of electrochemiluminescence (ECLIA) based numerical COI values with quantitative ELISA of anti-SARS-CoV-2 antibody.Design and Methods: Two hundred and twenty-eight (228) recovered COVID-19 patients were included; their serum samples were analyzed by quantitative ELISA and ECLIA for anti-SARSCOV- 2 antibodies.Results: One hundred and seventy-three (75.8%) patients tested positive by ECLIA and ELISA assay and thirty-seven (6.2%) were tested negative by both methods. A weak positive correlation (r=0.37) was found between numerical COI value of ECLIA with ELISA concentration, which was statistically significant with p<0.001. All values were dispersed on scatter plot and there was no significant linear relationship between ECLIA and ELISA assay.Conclusions: As both testing techniques are base upon the same immunological phenomena of detecting antibodies against nucleocapsid protein. We suggest that COI values are not meant to describe the immunity level of the individuals thus the physicians should not consider it as a quantitative value for antibody levels in COVID-19 patients.Significance for public healthMany laboratories in Pakistan are reporting numerical COI values, which ultimately created great confusion among the patients and physicians. These values are, used indiscriminately and wrongly compared to other testing systems which were in general intended to be used for quantitative analysis of the antibodies developed in the persons exposed to the virus. There had been obvious misunderstanding in the public including the healthcare sector when these different techniques were used indiscriminately without a proper orientation towards the utility and limitations of a given testing system. As a result, the different numerical COI values which were included in the laboratory reports of the test created a great havoc and raised suspicions about the certainty of the diagnostic techniques. This correlation is important because this number game has been talk of the town and lay person uses them to get the idea of one's own immunity status.

First real-world experience of Gam-COVID-Vac Sputnik V vaccine use

With the ongoing SARS-CoV-2 pandemic, the safety and efficacy of vaccine prophylaxis with new vaccines have become vital. Objective. To study tolerability and efficacy of the Gam-COVID-Vac (Sputnik V) vaccine in the short term in a real-world setting in the example of the Federal remote consulting center on vaccination against new coronavirus infection COVID-19 of National Medical Research Center for Therapy and Preventive Medicine. Materials and methods. We retrospectively analyzed data from the registration cards of the first 500 voluntary vaccination recipients who received two vaccine doses in October-December 2020. Serum immunoglobulin (Ig) M and G levels to SARS-CoV-2 were measured in 204 participants at baseline, at Day 21, and at Day 42 after the injection of component I of Gam-COVID-Vac vaccine. Test for SARS-CoV-2 coronavirus RNA in a nasopharyngeal and/or oropharyngeal mucosa smear was performed before injection of component I of the vaccine using real-time PCR method on a DT-96 amplifier (DNA-Technology, Russia) using SARSCoV-2/SARS-CoV reagent kit (DNA-Technology, Russia). Anti-SARS-CoV-2 IgG and IgM were measured using reagent kits for enzyme immunoassay (Vector-Best, Russia). Results. During the follow-up (42 days), none of the vaccine recipients experienced serious adverse events. During the first 14 days after receiving component I of the vaccine Gam-COVID-Vac, eight vaccine recipients got sick with COVID-19;the disease had a mild course and did not require hospital admission. On Day 21, no IgM antibodies were detected in any of the vaccine recipients, while the IgG level was detectable and the cutoff index (CI) was 11.3 [3.4;16.2]. On Day 42 after the injection of component I of the Gam-COVID-Vac vaccine, there was an increase in IgG levels, and CI was 16.2 [16.0;16.4] in most subjects, while no IgM levels were detected in any of the vaccine recipients tested. Conclusion. The data obtained may indicate a favorable tolerability and safety profile of the combined vector vaccine Gam-COVID-Vac, as well as short-term efficacy, according to the change of anti-SARS-CoV-2 IgG and absence of severe COVID-19 disease in vaccinated subjects during the follow-up period. To obtain further evidence of the long-term clinical efficacy of Gam-COVID-Vac, follow-up of vaccinated subjects should be continued. (English) [ABSTRACT FROM AUTHOR] Ð’ NƒN

Nature and Duration of Protective Antibodies Developed After COVID-19 Infection: Journal of Pediatric Infection

The specificity of tests that measure IgG antibody or IgM+IgG total antibodies is much higher than tests that measure IgM or IgA antibodies alone. [...]the measurement of IgA antibody level is not recommended for routine use. The Centers for Disease Control and Prevention (CDC) recommends that antibody tests with high specificity (99.5%) should be preferred primarily in the diagnosis of COVID-19. [...]the high sensitivity of the test used (the positive rate of a given test in a PCR confirmed COVID-19 patient) and high specificity (the negative rate of a given test in a patient without COVID-19) increases the accuracy of the test used. [...]it can be predicted that SARS CoV-2 infection with systemic symptoms may also lead to a longer-lasting immune response. [...]Roche Elecsys Anti-SARS-CoV-2 total semi-quantitative/qualitative test results with COI (cut-off index) level >109, Roche Elecsys Anti-SARS-CoV-2 quantitative total antibody test with level >132 IU/mL, Euroimmune anti-SARS-CoV-IgG semi-quantitative/qualitative test with ratio >3.5, determined as acceptable high antibody values, for the convalescent plasma pool.

Modeling the spectrum and composition of ultrahigh-energy cosmic rays with two populations of extragalactic sources

We fit the ultrahigh-energy cosmic-ray (UHECR, Egtrsim 0.1 EeV) spectrum and composition data from the Pierre Auger Observatory at energies Egtrsim 5cdot 10^{18} eV, i.e., beyond the ankle using two populations of astrophysical sources. One population, accelerating dominantly protons (^1H), extends up to the highest observed energies with maximum energy close to the GZK cutoff and injection spectral index near the Fermi acceleration model; while another population accelerates light-to-heavy nuclei (^4He, ^{14}N, ^{28}Si, ^{56}Fe) with a relatively low rigidity cutoff and hard injection spectrum. A significant improvement in the combined fit is noted as we go from a one-population to two-population model. For the latter, we constrain the maximum allowed proton fraction at the highest-energy bin within 3.5sigma statistical significance. In the single-population model, low-luminosity gamma-ray bursts turn out to match the best-fit evolution parameter. In the two-population model, the active galactic nuclei is consistent with the best-fit redshift evolution parameter of the pure proton-emitting sources, while the tidal disruption events could be responsible for emitting heavier nuclei. We also compute expected cosmogenic neutrino flux in such a hybrid source population scenario and discuss possibilities to detect these neutrinos by upcoming detectors to shed light on the sources of UHECRs.

Clinical implications of serum Mac-2-binding protein glycan isomer as a novel biomarker of advanced hepatic fibrosis in diabetes.

BackgroundAppropriate strategy for screening, identification, and linkage to care of patients with advanced fibrosis in the general population is a current issue. The aim of this study was to find reference values and the clinical role of Mac-2 binding protein glycan isomer (M2BPGi) in a health check-up setting.MethodsThis study was designed as cross-sectional study. Adult subjects (n=1,073) who underwent a health check-up were included in the final analysis, and 952 subjects with risk factors for liver disease and insufficient data were excluded. M2BPGi quantification was based on a lectin antibody sandwich immunoassay. Fatty liver was diagnosed using abdominal sonography.ResultsThe reference value of M2BPGi was 0.5–1.0 cut off index (COI) in the average risk group. Serum M2BPGi showed a positive correlation with metabolic parameters as well as age. Prevalence of abnormal M2BPGi (>1.0) was higher in low muscle mass (4.7%, vs. 17.4%, P=0.002), metabolic syndrome (14.2% vs. 30.4%, P=0.003), and hypertension (21.8%, vs. 58.7%, P<0.001) compared to healthy controls. M2BPGi was positively correlated with estimated fibrosis values such as FIB-4 (R=0.293, P<0.001) and NAFLD fibrosis score (R=0.248, P<0.001). Although the prevalence of advanced fibrosis in the total population was just 1.6% (FIB-4 >2.65), the prevalence of advanced fibrosis increased to 50% in the high M2BPGi (>1.0) group with diabetes. This value was 31.25 times higher than in the total population group.ConclusionsThe results indicated a high possibility of advanced hepatic fibrosis in diabetic subjects with abnormal M2BPGi level (>1.0).

An index based on deep learning-measured spleen volume on CT for the assessment of high-risk varix in B-viral compensated cirrhosis.

Deep learning enables an automated liver and spleen volume measurements on CT. The purpose of this study was to develop an index combining liver and spleen volumes and clinical factors for detecting high-risk varices in B-viral compensated cirrhosis. This retrospective study included 419 patients with B-viral compensated cirrhosis who underwent endoscopy and CT from 2007 to 2008 (derivation cohort, n = 239) and from 2009 to 2010 (validation cohort, n = 180). The liver and spleen volumes were measured on CT images using a deep learning algorithm. Multivariable logistic regression analysis of the derivation cohort developed an index to detect endoscopically confirmed high-risk varix. The cumulative 5-year risk of varix bleeding was evaluated with patients stratified by their index values. The index of spleen volume-to-platelet ratio was devised from the derivation cohort. In the validation cohort, the cutoff index value for balanced sensitivity and specificity (> 3.78) resulted in the sensitivity of 69.4% and the specificity of 78.5% for detecting high-risk varix, and the cutoff index value for high sensitivity (> 1.63) detected all high-risk varices. The index stratified all patients into the low (index value ≤ 1.63; n = 118), intermediate (n = 162), and high (index value > 3.78; n = 139) risk groups with cumulative 5-year incidences of varix bleeding of 0%, 1.0%, and 12.0%, respectively (p < .001). The spleen volume-to-platelet ratio obtained using deep learning-based CT analysis is useful to detect high-risk varices and to assess the risk of varix bleeding. • The criterion of spleen volume to platelet > 1.63 detected all high-risk varices in the validation cohort, while the absence of visible varix did not exclude all high-risk varices. • Visual varix grade ≥ 2 detected high-risk varix with a high specificity (96.5-100%). • Combining spleen volume-to-platelet ratio ≤ 1.63 and visual varix grade of 0 identified low-risk patients who had no high-risk varix and varix bleeding on 5-year follow-up.

Updates on management strategies of hepatitis B virus reactivation in patients with resolved hepatitis virus B infection undergoing immunosuppressive therapy in rheumatology and the current situation in Niigata Rheumatic Center

With the introduction of methotrexate, biological disease-modifying antirheumatic drugs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), the disease activity of patients with rheumatoid arthritis has been dramatically ameliorated. However, these drugs have strong immunosuppressive effects and can cause reactivation of hepatitis B virus (HBV) in patients with resolved HBV infection. Corticosteroids or immunosuppressants used for other connective tissue diseases or vasculitis also carry a risk of inducing reactivation of HBV. Therefore, every rheumatologist should know how to detect the resolved infection of HBV in patients with rheumatic diseases receiving immunosuppressive therapy and how to monitor it when resolved infection is revealed. Of note, the cut-off index was changed from 2.1 log copies/ml to 20 IU/ml (1.3 Log IU/ml) in 2017. Rheumatologists should start nucleic acid analog administration at reactivation of HBV while performing ongoing immunosuppressive therapy in order to prevent severe or fulminant hepatitis. A low titer of HBs antibody (Ab) or lack of HBs Ab is a risk factor of reactivation of HBV. However, the reactivation of HBV cannot be prevented by HBs Ab titers at baseline or changes overtime. Rheumatologists should recognize that every immunosuppressive therapy, regardless of the mode of action, has a potential risk of reactivation. To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged. Patients’ education, systems for checking electronic medical charts, and multidisciplinary efforts are considered important for detecting HBV reactivation.

Detection of SARS-CoV-2 Antibodies in Kidney Transplant Recipients.

Detection of SARS-CoV-2 Antibodies in Kidney Transplant Recipients.

Seroprevalence of COVID-19 in Taiwan revealed by testing anti-SARS-CoV-2 serological antibodies on 14,765 hospital patients

BackgroundCoronavirus Disease 2019 (COVID-19) has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 25 million cases with over 0•85 million deaths, as of September 2, 2020. Taiwan has been successful in countering the COVID-19 outbreak, however, the potential risk for asymptomatic infections and the prevalence rates remain unknown. We aimed to estimate the seroprevalence of COVID-19 in Taiwan via serologically testing hospital patients with neither symptoms indicative of nor positive nucleic acid test for SARS-CoV-2 infection. MethodsResidual specimens from laboratory blood tests for outpatient and emergency department patients visiting a medical centre in Taipei, Taiwan, within one week in May and another in July, 2020, were collected. We used Elecsys Anti-SARS-CoV-2 Assay to screen and further validated cases with high cutoff index by a confirmatory ELISA assay. We also analysed antibody responses against SARS-CoV-2 along disease progression in four nucleic acid test confirmed COVID-19 patients. FindingsBlood samples from a total of 14,765 patients were tested. The unweighted seroprevalence of anti-SARS-CoV-2 antibodies was 0•07% [95% CI, 0•04%-0•13%]; after weighting with the population demographics of Taiwan, the estimated overall seroprevalence was 0•05% [95% CI, 0•02%-0•10%]. Furthermore, based on data of the four COVID-19 cases, the seroconversion dates for IgM were as early as 9 days and that for IgG 11 days after symptoms onset. InterpretationWe screened the anti-SARS-CoV-2 antibodies in a small-scale population-based study and observed an approximately 0•05% seroprevalence of COVID-19, indicating that the current containment protocols emphasising mask wearing, hand washing, social distancing and mandatory quarantine for all incomers are effective in Taiwan. FundingTaipei Veterans General Hospital, Taipei, Taiwan.

Performance of an automated chemiluminescence SARS-CoV-2 IG-G assay

IntroductionWe describe our evaluation of the Abbott SARS-CoV-2 IgG assay on the Architect immunoassay analyser. MethodsWe assessed assay precision, sensitivity, specificity, positive/negative predictive values (PPV/NPV), cross-reactivity (influenza/dengue/hepatitis B and C/rheumatoid factor/anti-nuclear/double-stranded DNA/syphilis) and sample throughput in samples from real-time polymerase chain reaction (RT-PCR) positive patients/healthcare workers (HCWs)/pre-pandemic samples. We compared the cut-off indexes (COIs) between all control samples (HCWs and pre-pandemic) to generate an optimised COI limit for reactivity. ResultsThe assay specificity was 99.8% (n = 980) and sensitivity was 45.9–96.7% (n = 279). When tested ≥ 14 days post-positive RT-PCR (POS), the PPV/NPV was 96.4%/99.8%. The difference between the COIs of HCWs/pre-pandemic samples was small (0.01, p < 0.0001). There was minimal cross-reactivity with other antibodies. A lower COI limit for reactivity (≥0.55, using the 99th percentile COI of our controls and ROC analysis) improved diagnostic sensitivity, especially at 0–6 days POS (45.9–55.8%), with a small decrease in specificity (98.9%). The assay throughput was 100 samples in 70 min. ConclusionThe Abbott SARS-CoV-2 IgG assay shows excellent performance in patients ≥ 14 days POS. The difference between the COIs of HCWs and pre-pandemic samples was numerically small. A lower COI limit improves assay sensitivity with a slight decrease in specificity.