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Rapid increases in cases of COVID-19 were observed in multiple cities in Iran towards the start of the pandemic. However, the true infection rate remains unknown. We aimed to assess the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 18 cities of Iran as an indicator of the infection rate. In this population-based cross-sectional study, we randomly selected and invited study participants from the general population (from lists of people registered with the Iranian electronic health record system or health-care centres) and a high-risk population of individuals likely to have close social contact with SARS-CoV-2-infected individuals through their occupation (from employee lists provided by relevant agencies or companies, such as supermarket chains) across 18 cities in 17 Iranian provinces. Participants were asked questions on their demographic characteristics, medical history, recent COVID-19-related symptoms, and COVID-19-related exposures. Iran Food and Drug Administration-approved Pishtaz Teb SARS-CoV-2 ELISA kits were used to detect SARS-CoV-2-specific IgG and IgM antibodies in blood samples from participants. Seroprevalence was estimated on the basis of ELISA test results and adjusted for population weighting (by age, sex, and city population size) and test performance (according to our independent validation of sensitivity and specificity). From 9181 individuals who were initially contacted between April 17 and June 2, 2020, 243 individuals refused to provide blood samples and 36 did not provide demographic information and were excluded from the analysis. Among the 8902 individuals included in the analysis, 5372 had occupations with a high risk of exposure to SARS-CoV-2 and 3530 were recruited from the general population. The overall population weight-adjusted and test performance-adjusted prevalence of antibody seropositivity in the general population was 17·1% (95% CI 14·6–19·5), implying that 4 265 542 (95% CI 3 659 043–4 887 078) individuals from the 18 cities included were infected by the end of April, 2020. The adjusted seroprevalence of SARS-CoV-2-specific antibodies varied greatly by city, with the highest estimates found in Rasht (72·6% [53·9–92·8]) and Qom (58·5% [37·2–83·9]). The overall population weight-adjusted and test performance-adjusted seroprevalence in the high-risk population was 20·0% (18·5–21·7) and showed little variation between the occupations included. Seroprevalence is likely to be much higher than the reported prevalence of COVID-19 based on confirmed COVID-19 cases in Iran. Despite high seroprevalence in a few cities, a large proportion of the population is still uninfected. The potential shortcomings of current public health policies should therefore be identified to prevent future epidemic waves in Iran. Iranian Ministry of Health and Medical Education. For the Farsi translation of the abstract see Supplementary Materials section.

A randomized trial comparing ibrutinib plus rituximab with rituximab alone in patients with Waldenström’s macroglobulinemia showed significantly higher rates of progression-free survival and overall response with the addition of ibrutinib.

Tuberculosis (TB) is a major global health problem and the only currently-licensed vaccine, BCG, is inadequate. Many TB vaccine candidates are designed to be given as a boost to BCG; an understanding of the BCG-induced immune response is therefore critical, and the opportunity to relate this to circumstances where BCG does confer protection may direct the design of more efficacious vaccines. While the T cell response to BCG vaccination has been well-characterized, there is a paucity of literature on the humoral response. We demonstrate BCG vaccine-mediated induction of specific antibodies in different human populations and macaque species which represent important preclinical models for TB vaccine development. We observe a strong correlation between antibody titers in serum versus plasma with modestly higher titers in serum. We also report for the first time the rapid and transient induction of antibody-secreting plasmablasts following BCG vaccination, together with a robust and durable memory B cell response in humans. Finally, we demonstrate a functional role for BCG vaccine-induced specific antibodies in opsonizing mycobacteria and enhancing macrophage phagocytosis in vitro , which may contribute to the BCG vaccine-mediated control of mycobacterial growth observed. Taken together, our findings indicate that the humoral immune response in the context of BCG vaccination merits further attention to determine whether TB vaccine candidates could benefit from the induction of humoral as well as cellular immunity.

COVID-19 seroprevalence data, particularly in less developed countries with a relatively low incidence, has been scant. We aimed to explore the seroprevalence of hospital staff in the area with zero confirmed COVID-19 case to shed light on the situation of COVID-19 infection in zero or low infection rate countries where mass screening was not readily available. A locally developed rapid immunoglobulin M (IgM)/immunoglobulin G (IgG) test kit was used for hospital staff screening of Ranong hospital which is located in a province with zero COVID-19 prevalence in Thailand from 17th April to 17th May 2020. All staff was tested, 100 of which were randomly invited to have a repeating antibody test in one month. (Thai Clinical Trials Registry: TCTR20200426002). Of 844 hospital staff, 82 were tested twice one month apart (response rate for repeating antibody test 82%). Overall, 0.8% of the participants (7 of 844) had positive IgM, none had positive IgG. Female staff had 1.0% positive IgM (95% CI: 0.5-2.1%) while male had 0.5% positive IgM (95% CI: 0.1-2.6%). No participants with a history of travel to the high-risk area or close contact with PCR-confirmed COVID-19 case developed SARS-CoV-2 antibodies. Among 844 staff, 811 had no symptoms and six of them developed IgM seropositive (0.7%) while 33 had minor symptoms and only one of them developed IgM seropositive (3.0%). No association between SARS-CoV-2 IgM status and gender, history of travel to a high-risk area, close contact with PCR-confirmed or suspected COVID-19 case, presence of symptoms within 14 days, or previous PCR status was found. None of the hospital staff developed SARS-CoV-2 IgG. COVID-19 antibody test could detect a considerable number of hospital staff who could be potential silent spreaders in a province with zero COVID-19 cases. Accurate antibody testing is a valuable screening tool, particularly in asymptomatic healthcare workers. Trial registration: This study was approved by the Institutional Review Board of Chulalongkorn University (IRB No.236/63) and the Institutional Review Board of Ranong Hospital. (Thai Clinical Trials Registry: TCTR20200426002).

PCR methods are presently the standard for the diagnosis of Coronavirus disease 2019 (COVID-19), but additional methodologies are needed to complement PCR methods, which have some limitations. Here, we validated and investigated the usefulness of measuring serum antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the iFlash3000 CLIA analyzer. We measured IgM and IgG titers against SARS-CoV-2 in sera collected from 26 PCR-positive COVID-19 patients, 53 COVID-19-suspected but PCR-negative patients, and 20 and 100 randomly selected non-COVID-19 patients who visited our hospital in 2020 and 2017, respectively. The repeatability and within-laboratory precision were obviously good in validations, following to the CLSI document EP15-A3. Linearity was also considered good between 0.6 AU/mL and 112.7 AU/mL for SARS-CoV-2 IgM and between 3.2 AU/mL and 55.3 AU/mL for SARS-CoV-2 IgG, while the linearity curves plateaued above the upper measurement range. We also confirmed that the seroconversion and no-antibody titers were over the cutoff values in all 100 serum samples collected in 2017. These results indicate that this measurement system successfully detects SARS-CoV-2 IgM/IgG. We observed four false-positive cases in the IgM assay and no false-positive cases in the IgG assay when 111 serum samples known to contain autoantibodies were evaluated. The concordance rates of the antibody test with the PCR test were 98.1% for SARS-CoV-2 IgM and 100% for IgG among PCR-negative cases and 30.8% for SARS-CoV-2 IgM and 73.1% for SARS-CoV-2 IgG among PCR-positive cases. In conclusion, the performance of this new automated method for detecting antibody against both N and S proteins of SARS-CoV-2 is sufficient for use in laboratory testing.

Traditional right ventricular apical pacing can, over time, result in deterioration of left ventricular function. In this comparative-effectiveness trial, biventricular pacing prevented the reduction in left ventricular ejection fraction that is seen with right ventricular pacing. The findings have implications for the treatment of patients with bradycardia who require permanent pacing. This phase 2 study evaluated the role of B-lymphocyte depletion with rituximab in type 1 diabetes mellitus. Rituximab partially preserved beta-cell function over a 1-year period, suggesting that B lymphocytes contribute to the pathogenesis of type 1 diabetes mellitus. The autoimmune destruction of beta cells in patients with type 1 diabetes mellitus begins before the onset of hyperglycemia, but measurement of C-peptide responses at the time of diagnosis indicates that patients retain some beta-cell function at this stage. Furthermore, the persistence of residual beta-cell function is associated with reductions of severe hypoglycemic episodes and complications. 1 Thus, an intervention that maintains endogenous insulin production might improve the management of type 1 diabetes and reduce long-term complications. Although the presence of autoantibodies is a diagnostic criterion, the immunopathogenesis of beta-cell destruction in type 1 diabetes is typically associated with T-lymphocyte autoimmunity. . . .

Background. Treatment with pegylated interferon (peg-IFN) alfa-2a (40KD) results in hepatitis B \"e\" antigen (HBeAg) seroconversion 6 months after treatment in up to 36% of HBeAg-positive chronic hepatitis B patients. This study explored the efficacy of a novel combination of peg-IFN alfa-2a and entecavir (ETV), a potent nucleoside analogue. Methods. In total, 218 treatment-naive Chinese HBeAg-positive patients were randomized to peg-IFN alfa-2a (180 μg/week) for 48 weeks, either as monotherapy (n = 72), or with 24 weeks of ETV (0.5 mg/daily) added at week 13 (ETV add-on, n = 73), or pretreatment with a 24-week course of ETV, starting peg-IFN alfa-2a at week 21 (ETV pretreatment, n = 73). The primary endpoint was reduction in quantitative HBeAg from baseline to 24 weeks posttreatment. Results. Significant reductions in HBeAg from baseline were achieved in all treatment groups 24 weeks posttreatment; reductions were comparable across treatment arms (shown as log10 Paul Ehrlich international units [PEIU]/mL): monotherapy: −1.4 (SD, 1.8); ETV add-on: −1.6 (SD, 1.8); ETV pretreatment: −1.3 (SD, 1.7). Rates of HBeAg seroconversion were similar across treatment groups posttreatment (monotherapy: 22 [31%]; ETV add-on: 18 [25%]; ETV pretreatment: 19 [26%]). Significantly greater reductions of hepatitis B virus DNA were achieved with ETV add-on while on treatment, but were not sustained posttreatment. Safety profiles were comparable between treatment groups; adverse events were experienced by 62 (86%) monotherapy, 65 (89%) ETV add-on, and 58 (81%) ETV pretreatment patients. Conclusions. Neither ETV add-on nor ETV pretreatment demonstrated superiority compared with 48 weeks of peg-IFN alfa-2a monotherapy. The optimal treatment strategy using nucleos(t)ide analogues and peg-IFN alfa-2a remains to be determined.

Background Our aim was to investigate the influence of FTS on human cellular and humoral immunity using a randomized controlled clinical study in esophageal cancer patients. Methods Between October 2013 and December 2014, 276 patients with esophageal cancer in our department were enrolled in the study. The patients were randomized into two groups: FTS pathway group and conventional pathway group. The postoperative hospital stay, hospitalization expenditure, and postoperative complications were recorded. The markers of inflammatory and immune function were measured before operation as well as on the 1st, 3rd, and 7th postoperative days (POD), including serum level of interleukin-6 (IL-6), C-reactive protein (CRP), serum globulin, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA) and lymphocyte subpopulations (CD3 lymphocytes, CD4 lymphocytes, CD8 lymphocytes and the CD4/CD8 ratio) in the patients between the two groups. Results In all, 260 patients completed the study: 128 in the FTS group and 132 in the conventional group. We found implementation of FTS pathway decreases postoperative length of stay and hospital charges ( P  < 0.05). In addition, inflammatory reactions, based on IL-6 and CRP levels, were less intense following FTS pathway compared to conventional pathway on POD1 and POD3 ( P  < 0.05). On POD1 and POD3, the levels of IgG, IgA, CD3 lymphocytes, CD4 lymphocytes and the CD4/CD8 ratio in FTS group were significantly higher than those in control group (All P  < 0.05). However, there were no differences in the level of IgM and CD8 lymphocytes between the two groups. Conclusions FTS improves postoperative clinical recovery and effectively inhibited release of inflammatory factors via the immune system after esophagectomy for esophageal cancer. Trial registration ChiCTR-TRC-13003562 , the date of registration: August 29, 2013.

Cholera is an acute voluminous dehydrating diarrheal disease caused by toxigenic strains of Vibrio cholerae O1 and occasionally O139. A growing body of evidence indicates that immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae are involved in mediating protection against cholera. We therefore assessed whether antibody responses against OSP occur after vaccination with live attenuated oral cholera vaccine CVD 103-HgR, and whether such responses correlate with protection against cholera. We assessed adult North American volunteers (n = 46) who were vaccinated with 5 × 108 colony-forming units (CFU) of oral cholera vaccine CVD 103-HgR and then orally challenged with approximately 1 × 105 CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961, either 10 or 90 days post-vaccination. Vaccination was associated with induction of significant serum IgM and IgA anti-OSP and vibriocidal antibody responses within 10 days of vaccination. There was significant correlation between anti-OSP and vibriocidal antibody responses. IgM and IgA anti-OSP responses on day 10 following vaccination were associated with lower post-challenge stool volume (r = -0.44, P = 0.002; r = -0.36, P = 0.01; respectively), and none of 27 vaccinees who developed a ≥1.5 fold increase in any antibody isotype targeting OSP on day 10 following vaccination compared to baseline developed moderate or severe cholera following experimental challenge, while 5 of 19 who did not develop such anti-OSP responses did (P = 0.01). Oral vaccination with live attenuated cholera vaccine CVD 103-HgR induces antibodies that target V. cholerae OSP, and these anti-OSP responses correlate with protection against diarrhea following experimental challenge with V. cholerae O1. ClinicalTrials.gov NCT01895855.

Background: Zoonotic risks in exposed students are poorly documented in Belgium. According to the literature, even though human tick-borne encephalitis (TBE) infection risk has increased significantly in southern Belgium, no previous human serological survey has demonstrated specific antibodies directed at TBE virus. Methods and principal findings: The aim of this paper was to perform a representative serological survey on sera involving students at the University of Liege, in the southern part of Belgium, to discover possible exposure to TBEV. A total of 207 sera samples were randomly chosen and analyzed using ELISA IgM (with 1 positive student out of 207) and ELISA IgG (with 10 positive students out of 207), subsequent serial immunofluorescence antibody testing (IFAT) IgG (with 8 positive students out of 10 positive in ELISA IgG) and serial IFAT IgM (with 1 negative student out of 1 positive in ELISA IgM), and confirmatory tests, i.e., 50% and 90% plaque reduction neutralization tests (PRNTs) (1 strongly positive student out of 8 positive in IFAT). Conclusions and significance: The exposure of students from the southern part of Belgium (area with increasing risk) to TBEV was assessed for the first time. Antibodies against TBEV could only be demonstrated in 1 out of 207 students. This finding contributes to better decision-making in public health and prevention and management of tick-borne diseases in the context of climate change. Awareness among all students should be prioritized, with prevention measures against tick bites, particularly during forest and recreational activities contributing to risk, to maintain the current low seroprevalence levels.