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• Using a novel multiplex assay, we longitudinally analyzed the genoprevalence of 13 diverse Human polyomaviruses (HPyVs) in in kidney transplant recipients (KTRs). • We specifically included KTRs with high level BK (BKPyV) and JC (JCPyV) virus DNAemia and Polyomavirus associated nephroptahy (PVAN). In total, we analyzed 400 serum and 388 urine samples obtained pairwise from 99 KTRs during the post-transplant follow-up. • Three different recently discovered non-BKPyV/JCPyV HPyVs, Human Polyomavirus 9, Merkel cell Polyomavirus (MCPyV) and Trichodysplasia spinulosa associated Polyomavirus, were detected in 11 blood and 21 urine samples from 21 patients. • DNAemia of these viruses occurred frequently during high level BKPyV DNAemia and PVAN. However, no statistically significant increase of the detection frequency was observed due to progression of BKPyV replication for blood samples. • Of note, the detection rate of MCPyV in urine was significantly higher during BKPyV DNAemia in KTRs with histologically verified PVAN. While the pathogenicity of the two initially identified Human Polyomaviruses (HPyVs), BK Virus (BKPyV) and JC Virus (JCPyV) has been intensely studied, there is only limited data, on whether the occurrence of the recently discovered HPyVs correlates with high level BKPyV replication and progression towards Polyomavirus associated nephropathy (PVAN). Therefore, we performed a comprehensive longitudinal genoprevalence analysis of 13 HPyVs using a novel multiplex assay including 400 serum and 388 urine samples obtained from 99 kidney transplant recipients (KTRs), grouped by quantitative BKPyV DNA loads and evidence of manifest BKPyV associated disease (histologically verified PVAN, high urinary decoy cell levels and concurrent decrease of renal function). In total, 3 different non-BKPyV/JCPyV HPyVs, Human Polyomavirus 9, Merkel Cell Polyomavirus (MCPyV) and Trichodysplasia Spinulosa associated Polyomavirus were detected in 11 blood and 21 urine samples from 21 patients. Although DNAemia of these viruses occurred more frequently during high level BKPyV DNAemia and PVAN, the increase of the detection frequency due to progression of BKPyV replication did not reach statistical significance for blood samples. The positive detection rate of MCPyV in urine, however, was significantly higher during BKPyV DNAemia in 19 KTRs of our cohort who suffered from histologically verified PVAN (p = 0.005). In one individual with PVAN, continuous long-term shedding of MCPyV in urine was observed. In our cohort the recently discovered HPyVs HPyV9, TSPyV and MCPyV emerged in blood from KTRs with variable kinetics, while detection of MCPyV DNAuria occurred more frequently during BKPyV DNAemia in patients with PVAN. [ABSTRACT FROM AUTHOR]

Background: Drug-induced immunosuppression in kidney transplant recipients is crucial to prevent allograft rejection, but increases risk for infectious disease. Immunologic monitoring to tailor immunosuppressive drugs might prevent alloreactivity and adverse effects simultaneously. The apathogenic torque teno virus (TTV) reflects the immunocompetence of its host and might act as a potential candidate for a holistic monitoring.Methods: We screened all 1010 consecutive patients from the prospective Vienna Kidney Transplant Cohort Study for availability of allograft biopsies and adequately stored sera for TTV quantification by polymerase chain reaction.Results: Patients with acute biopsy-proven alloreactivity according to the Banff classification (n = 33) showed lower levels of TTV in the peripheral blood compared to patients without rejection (n = 80) at a median of 43 days before the biopsy. The risk for alloreactivity decreased by 10% per log level of TTV copies/mL (risk ratio, .90 [95% confidence interval, .84-.97]; P = .005). TTV levels >1 × 106 copies/mL exclude rejection with a sensitivity of 94%. Multivariable generalized linear modeling suggests an independent association between TTV level and alloreactivity.Conclusions: TTV is a prospective biomarker for risk stratification of acute biopsy-proven alloreactivity in kidney transplant recipients and might be a potential tool to tailor immunosuppressive drug therapy. [ABSTRACT FROM AUTHOR]

Background & Aims: Increasing numbers of autochthonous hepatitis E virus infections have been reported in Europe. Chronic infections have been shown in immune‐compromised patients after solid organ transplantation. Hepatitis E virus might be a possible trigger for autoimmune hepatitis and might cause disease flares or relapses in the further course of disease. Aim of this study was to investigate the presence of hepatitis E virus antibodies and hepatitis E virus RNA, and to analyse their impact on immunosuppressive treatment in patients with autoimmune hepatitis. Methods: Sera from 92 autoimmune hepatitis patients (73/79.3% female, age: 42.2 ± 16.3 years [mean ± SD]) were tested. Patients were scored according to the simplified and revised scoring systems of the International Autoimmune Hepatitis Group. The prevalence of anti‐ hepatitis E virus antibodies (Beijing Wantai Biological Pharmacy Enterprises Co., Ltd, Beijing, China) and hepatitis E virus RNA was determined. Results: 19/20.7% autoimmune hepatitis patients tested positive for hepatitis E virus‐IgG, which was higher than in previous reports of healthy Austrian individuals (12.4%, P = 0.031); hepatitis E virus RNA was not detectable in any patient. Anti‐hepatitis E virus positive patients were older (49.5 ± 9.5 vs 40.4 ± 17.2 years [mean ± SD], P = 0.033) but did not differ in laboratory findings at diagnosis (AST: 14.6 [1.3‐70.6] vs 9.5 [0.7‐62.7] × ULN [median/range]; P = 0.387, alanine aminotransferase: 18.3 [1.6‐62.7] vs. 12.9 [0.8‐62.6] × ULN; P = 0.511; IgG: 1.4 [1.0‐2.5] vs 1.3 [0.6‐3.8] g/dL × ULN; P = 0.278) nor in alanine aminotransferase levels after six months (0.7 [0.5‐2.4] vs 1.0 U/L × ULN [0.1‐22.4]; P = 0.077). Conclusions: No chronic hepatitis E virus infection was observed in our cohort of autoimmune hepatitis patients. Anti‐ hepatitis E virus‐IgG positive patients were older and the seroprevalence was nearly twice as high as reported previously in healthy Austrian individuals, suggesting that hepatitis E virus‐infection might act as trigger for the development of autoimmune hepatitis. [ABSTRACT FROM AUTHOR]

Background: Drug-induced immunosuppression following kidney transplantation is crucial to prevent allograft rejection, but increases risk for infectious disease. Tailoring of drug dosing to prevent both rejection and infection is greatly desirable. The apathogenic and ubiquitous torque teno virus (TTV) reflects immunocompetence of the host and might be a potential candidate for immunologic monitoring.Methods: To assess TTV as an infection biomarker, virus load was prospectively quantified in peripheral blood of 169 consecutive renal allograft recipients at the Medical University Vienna.Results: Patients with infection showed higher TTV levels compared to patients without infection (4.2 × 108 copies/mL [interquartile range, IQR, 2.7 × 107-1.9 × 109] vs 2.9 × 107 [IQR 1.0 × 106-7.2 × 108]; P = .006). Differences in TTV load became evident almost 3 months before infection (median 77 days, IQR 19-98). Each log level of TTV copies/mL increased the odds ratio for infection by 23% (95% confidence interval 1.04-1.45; P = .014). TTV >3.1 × 109 copies/mL corresponded to 90% sensitivity to predict infections. Logistic regression demonstrated independent association between TTV levels and infection.Conclusions: TTV quantification predicts infection after kidney transplantation and might be a potential tool to tailor immunosuppressive drug therapy. [ABSTRACT FROM AUTHOR]

Background and Aims: Monitoring of chronic Hepatitis C (CHC) treatment relies on HCV RNA quantification by means of real-time PCR methods. Assay specific analytical sensitivities may impact therapy management. Methods: Comparative analysis between three commercial assays (Roche COBAS AmpliPrep/COBAS TaqMan Version 1 (CAP/CTM Ver. 1), Version 2 (CAP/CTM Ver. 2) and the Abbott RealTime HCV (ART) assay) was performed on 247 available samples taken at key decision time points during antiviral therapy of 105 genotype 1 patients (triple therapy: n = 70; dual therapy: n = 35). Results: Overall concordance of HCV RNA measurements was high between the two Roche systems (89%; n = 220/247) but lower between the Roche assays and the ART (CAP/CTM Ver. 1 vs ART: 77.3%; n = 191/247 and CAP/CTM v.2 vs ART: 80.1%; n = 198/247). Most discrepancies were noted in week 4/8 samples with residual viremia (

Hemophagocytic lymphohistiocytosis (HLH) is an excessive immune activation with cytokine storm und multi-organ dysfunction. It can occur secondarily, especially due to viral infections like COVID-19. Rapid treatment is crucial for favourable outcomes, but diagnosing HLH is challenging. The most common diagnostic instrument is the H-Score. However, the prognostic value of the H-score has not yet been assessed in detail in the spotlight of secondary HLH in severe COVID-19. COVID-19 patients treated between February 2020 and April 2021 at the intensive care unit (ICU) of the Department of Infectious Diseases and Tropical Medicine, Clinic Favoriten, Vienna, Austria, were included in this study. Data were assessed retrospectively by document review, and the follow-up period was at least 90 days. A total of 208 critically ill COVID-19 patients with an age of 61.8 ± 13.6 years were enrolled in this study. We found an average H-Score in the entire study collective of 94 ± 51 points, and 8.7% had a score ≥ 169 testing positive for HLH. A positive score was associated with increased mortality rates at 28 (66.7 vs. 26.3%, p < 0.001) and 90 days (72.2 vs. 27.9%, p < 0.001). In our cohort study, critically ill COVID-19 patients with an H-Score ≥ 169 during their ICU stay had increased mortality rates at 28 and 90 days. Thus, attention should be paid to individuals with rising or high scores. Therapeutic options and their impact on mortality for patients with COVID-19-associated secondary HLH should be evaluated in further studies. [ABSTRACT FROM AUTHOR]

Background and Aims: Identification of people living with hepatitis C virus (HCV) via readily available laboratory records could be a key strategy for macro‐elimination, aligning with the WHO elimination goal. Therefore, the ELIMINATE(ELIMINation of HCV in AusTria East) project aimed to systematically re‐link people with a 'last‐positive' HCV‐RNA PCR record to care. Methods: In 10 major liver centres in Eastern Austria, a systematic readout of 'last‐positive' HCV‐RNA PCR test records obtained between 2008 and 2020 were conducted and linked to available patient contact data. Between 2020 and 2023, individuals were contacted first by phone, then by letter, to inform them about the availability of effective direct‐acting antiviral (DAA) treatment and invite them for pre‐treatment evaluation. Results: The overall cohort of last‐positive HCV+ individuals included 5695 subjects (62.5% males, mean age 57.3 ± 17.3 years); of note, 1931 (34%) of them had died and 759 (13%) individuals had no valid contact information. Of the remaining 3005 individuals, 1171 (40.0%) had already achieved sustained virological response (SVR) at the time of re‐call. We successfully reached 617 (20.5%), of whom 417 (67.6%) attended their pre‐treatment visit, and 397 (64.3%) commenced DAA‐therapy. HCV cure has been confirmed in 326 individuals, corresponding to an SVR rate of 82.1%. Conclusion: The ELIMINATE project identified 5695 people living with HCV who were 'lost to care' despite documented HCV viraemia. While invalid contact data were an evident barrier to HCV elimination, premature deaths among the cohort underscored the severity of untreated HCV. The implementation of a systematic HCV‐RNA PCR recorded‐based re‐call workflow represents an effective strategy supporting the WHO goal of HCV elimination. [ABSTRACT FROM AUTHOR]

Background: The 2022 mpox outbreak continues, and while progress has been made in prevention strategies and potential treatment options, data on late sequelae following mpox are scarce. Objective: This analysis aimed to assess the incidence of scar formation in individuals affected by the 2022 mpox outbreak. Methods: All individuals diagnosed with mpox at the Department of Dermatology at the Medical University of Vienna in 2022 were included in this analysis. Follow‐up data were collected throughout November 2023. 'Scar formation' was defined as having at least one scar at the former active mpox lesions. Results: At our clinic, 28 cases of mpox presented between June 2022 and October 2022 and exclusively occurred in men who have sex with men (100%, 28/28), of whom 46% (13/28) were living with HIV, and 32% (9/28) were using pre‐exposure prophylaxis (PrEP). Secondary bacterial infection of mpox lesions was suspected in six individuals, and all received systemic antibiotics. Overall, 26 were followed up in November 2023 after a median time of 15 months, and scar formations were found in 43% of cases. Conclusions: Our data provide insights into the late yet cumulating disease burden caused by the 2022 mpox outbreak. Highly effective prevention strategies are warranted to overcome the mpox epidemic and its potential late sequelae. [ABSTRACT FROM AUTHOR]

Background: The 2022 outbreak of monkeypox virus (MPXV) revealed new transmission routes. Incidence declined sharply in September 2022, and it remains unclear whether MPXV is circulating in asymptomatic individuals because of increased immunity. Objectives: Our study aimed to assesss the number of asymtomatic MPXV carriers in individuals at high risk for STI. Methods: We analysed anal samples from asymptomatic highly sexually active men who have sex with men for the presence of MPXV. Results: We detected a high number of concomitant sexually transmitted infections but did not find a single sample with MPXV. Conclusions: Our results indicate that the general recommendation to implement screening for MPXV is not currently justified. [ABSTRACT FROM AUTHOR]

This study presents a graphene field-effect transistor (gFET) biosensor with dual detection capabilities for SARS-CoV-2: one RNA detection assay to confirm viral positivity and the other for nucleocapsid (N-)protein detection as a proxy for infectiousness of the patient. This technology can be rapidly adapted to emerging infectious diseases, making an essential tool to contain future pandemics. To detect viral RNA, the highly conserved E-gene of the virus was targeted, allowing for the determination of SARS-CoV-2 presence or absence using nasopharyngeal swab samples. For N-protein detection, specific antibodies were used. Tested on 213 clinical nasopharyngeal samples, the gFET biosensor showed good correlation with RT-PCR cycle threshold values, proving its high sensitivity in detecting SARS-CoV-2 RNA. Specificity was confirmed using 21 pre-pandemic samples positive for other respiratory viruses. The gFET biosensor had a limit of detection (LOD) for N-protein of 0.9 pM, establishing a foundation for the development of a sensitive tool for monitoring active viral infection. Results of gFET based N-protein detection corresponded to the results of virus culture in all 16 available clinical samples and thus it also proved its capability to serve as a proxy for infectivity. Overall, these findings support the potential of the gFET biosensor as a point-of-care device for rapid diagnosis of SARS-CoV-2 infection and indirect assessment of infectiousness in patients, providing additional information for clinical and public health decision-making. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic necessitates healthcare restrictions that also affected ongoing hepatitis C virus (HCV) elimination efforts. We assessed the value of a physician‐operated HCV hotline on treatment and cure rates throughout the pandemic. All HCV patients undergoing HCV therapy at the Vienna General Hospital from 2019 to 2021 were included. An HCV hotline was established in 2019 and provided services including phone calls, text messages and voicemails. Patients were stratified by date of HCV therapy: 2019 (pre‐COVID) vs. 2020/2021 (during‐COVID) and use of the HCV hotline: users vs. non‐users. Overall, 220 patients were included (pre‐COVID: n = 91 vs. during‐COVID: n = 129). The prevalence of intravenous drug use (60.5%) and alcohol abuse (24.8%) was high during COVID. During COVID, the number of DAA treatment starts declined by 24.2% (n = 69) in 2020 and by 34.1% (n = 60) in 2021 vs. pre‐COVID (n = 91, 100%). Significantly more patients used the HCV hotline during‐COVID (95.3%) vs. pre‐COVID (65.9%; p <.001). Sustained virologic response (SVR) was 84.6% pre‐COVID and 86.0% during‐COVID. HCV hotline users achieved higher SVR rates during‐COVID (88.2% vs. 33.3%, p =.004), but also pre‐COVID (96.7% vs. 61.3%, p <.001) compared with non‐users. Considering only patients with completed DAA treatments, SVR rates remained similarly high during‐COVID (96.9%) versus pre‐COVID (98.1%). HCV treatment initiations decreased during‐COVID but importantly, nearly all DAA‐treated HCV patients used the HCV hotline during the COVID pandemic. Overall, the SVR rate remained at 88.2% during COVID and was particularly high in HCV phone users—most likely due to facilitation of adherence. [ABSTRACT FROM AUTHOR]

Results of earlier external quality assessment (EQA) rounds suggested remarkable differences in the sensitivity of SARS-CoV PCR assays. Although the test systems are intended to detect SARS-CoV-2 in individual samples, screening is often applied to sample pools to increase efficiency and decrease costs. However, it is unknown to what extent these tests actually meet the manufacturer's specifications for sensitivity and how they perform when testing sample pools. The sensitivity of assays in routine use was evaluated with a panel of positive samples in a round of a SARS-CoV-2 virus genome detection EQA scheme. The panel consisted of samples at or near the lower limit of detection ("weakly positive"). Laboratories that routinely test sample pools were asked to also analyze the pooled EQA samples according to their usual pool size and dilution method. All participants could detect a highly positive patient-derived sample (>106 copies/mL). Most (96%) of the test systems could detect at least 1,000 copies/mL, meeting the minimum acceptable benchmark, and many (94%) detected the vRNA in a sample with lower concentration (500 copies/mL). The false negative ratio increased to 16 and 26% for samples with 100 and 50 copies/mL, respectively. The performance of most assays met or exceeded their specification on sensitivity. If assays are to be used to analyze sample pools, the sensitivity of the assay and the number of pooled samples must be balanced. [ABSTRACT FROM AUTHOR]

Background and Aims: The coronavirus disease of 2019 (COVID‐19) causes considerable mortality worldwide. We aimed to investigate the frequency and predictive role of abnormal liver chemistries in different age groups. Methods: Patients with positive severe acute respiratory distress syndrome‐coronavirus‐2 (SARS‐CoV‐2) polymerase chain reaction (PCR) test between 03/2020‐07/2021 at the Vienna General Hospital were included. Patients were stratified for age: 18–39 vs. 40–69 vs. ≥70 years (y). Aspartate aminotransferase (AST), alanine‐aminotransferase (ALT), alkaline phosphatase (ALP), gamma‐glutamyl transferase (GGT) and total bilirubin (BIL) were recorded. Results: 900 patients (18–39 years: 32.2%, 40–69 years: 39.7%, ≥70 years: 28.1%) were included. Number of comorbidities, median D‐dimer and C‐reactive protein increased with age. During COVID‐19, AST/ALT and ALP/GGT levels significantly increased. Elevated hepatocellular transaminases (AST/ALT) and cholestasis parameters (ALP/GGT/BIL) were observed in 40.3% (n = 262/650) and 45.0% (n = 287/638) of patients respectively. Liver‐related mortality was highest among patients with pre‐existing decompensated liver disease (28.6%, p <.001). 1.7% of patients without pre‐existing liver disease died of liver‐related causes, that is consequences of hepatic dysfunction or acute liver failure. Importantly, COVID‐19‐associated liver injury (16.0%, p <.001), abnormal liver chemistries and liver‐related mortality (6.5%, p <.001) were most frequent among 40–69 years old patients. Elevated AST and BIL after the first positive SARS‐CoV‐2 PCR independently predicted mortality in the overall cohort and in 40–69 years old patients. Conclusions: Almost half of the COVID‐19 patients exhibit abnormal hepatocellular and cholestasis‐related liver chemistries with 40–69 years old patients being at particularly high risk for COVID‐19‐related liver injury and liver‐related mortality. Elevated AST and BIL after SARS‐CoV‐2 infection are independent predictors of mortality, especially in patients aged 40–69 years. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has resulted in the disruption of healthcare systems. Vienna General Hospital (VGH), a tertiary hospital located in Austria, ran at almost full capacity despite high levels of community SARS-CoV-2 transmission and limited isolation room capacity. To ensure safe patient care, a bundle of infection prevention and control (IPC) measures including universal pre-admission screening and serial SARS-CoV-2 testing during hospitalization was implemented. We evaluated whether testing as part of our IPC approach was effective in preventing hospital outbreaks during different stages of the pandemic. Methods: In this retrospective single center study, we analyzed the SARS-CoV-2 PCR test results of cases admitted to VGH between a low (15/05/2020–01/08/2020) and a high incidence period (15/09/2020–18/05/2021). Outcomes were the diagnostic yield of (a) admission screening, (b) the yield of serial testing during hospitalization and (c) the occurrence of healthcare-associated COVID-19 (HA-COVID-19) and SARS-CoV-2 related hospital outbreaks. Results: The admission test positivity rate was 0.2% during the low and 2.3% during the high incidence phase. Regarding test conversions, 0.04% (low incidence phase) and 0.5% (high incidence phase) of initially negative cases converted to a positive test result within 7 days after admission The HA-COVID-19 incidence rate per 100,000 patient days was 1.0 (low incidence phase) and 10.7 (high incidence phase). One COVID-19 outbreak affecting eight patients in total could be potentially ascribed to the non-compliance with our IPC protocol. Conclusion: Testing in conjunction with other IPC measures enabled the safe provision of patient care at a hospital with predominantly shared patient rooms despite high case numbers in the community. [ABSTRACT FROM AUTHOR]

The identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen or RNA in respiratory specimens ≥14 days after administration of all recommended doses of authorized coronavirus disease 2019 (COVID-19) vaccines is defined as breakthrough infection. In the present investigation, mRNA and vector-based SARS-CoV-2 vaccines were analysed with respect to postvaccination infections in vaccinated hospital employees. A total of 8553 staff members were vaccinated with BNT162b2 (47%) or ChAdOx1-S (53%) between January and May 2021. In a retrospective observational cohort study, incidence of SARS-CoV-2 postvaccination infections was analysed in relation to demographic data, viral load, virus variants, vaccine brand and vaccination status at time of positive PCR test (fully vaccinated: ≥14 days since second dose; partially vaccinated: >21 days since first, but <14 days after second dose; insufficiently vaccinated: <22 days since first dose). Within the follow-up period, ending on 31 July 2021, person-time at risk-adjusted monthly rates for SARS-CoV-2 postvaccination infections were 0.18% (BNT162b2) and 0.57% (ChAdOx1-S) for insufficiently vaccinated, 0.34% (BNT162b2) and 0.32% (ChAdOx1-S) for partially vaccinated and 0.06% (BNT162b2) and 0.04% (ChAdOx1-S) for fully vaccinated participants. The two vaccine types did not differ with respect to hazard ratios for any of the respective postvaccination infection types. No cases of COVID-19-related hospitalizations or deaths were reported. Genotyping of positive PCR specimens revealed 42 variants of concern: B.1.1.7 (Alpha variant; n = 34); B.1.351 (Beta variant; n = 2), B.1.617.2 (Delta variant; n = 6). BNT162b2 and ChAdOx1-S are both effective in preventing breakthrough infections; however, it seems important, that all recommended vaccine doses are administered. [ABSTRACT FROM AUTHOR]

Background and Aims: Despite vaccination recommendations, hepatitis B (HBV) and D (HDV) coinfections are common in HIV+individuals. Methods: HBV immunization status (anti‐HBs) as well as HBV (HBsAg/HBV‐DNA) and HDV (anti‐HDV) coinfection rates were assessed in 1870 HIV+individuals at HIV diagnosis (baseline, BL) and last follow‐up (FU). Results: Sixty‐eight (3.6%) HIV patients were never tested for HBV. At BL, 89/1802 (4.9%) HIV patients were HBV coinfected. Four hundred and fifteen (23.0%) showed virological HBV clearance [HBsAg(‐)/anti‐HBc(+)/anti‐HBs(+)] and 210 (11.7%) presented with anti‐HBc(+) only. Seven hundred and ten (39.4%) were HBV naïve [HBsAg(‐)/anti‐HBs(‐)/anti‐HBc(‐)/HBV‐DNA(‐)], but only 378 (21.0%) received vaccinations with detectable anti‐HBs(+) titres. Among the 89 HBV/HIV‐coinfected patients, only 52 (58.4%) were tested for HDV: 11/49 (22.4%) had anti‐HDV(+) and 3/12 (25.0%) showed HDV‐RNA viraemia. During a median FU of 6.5 (IQR 7.2) years, 44 (4.6%) of the 953 retested BL HBV‐negative patients acquired new HBV infection (including 15/304, 4.9% of vaccinated patients). Of the 89 patients, 22 (24.7%) patients cleared their HBsAg, resulting in 60/1625 (3.7%) HIV/HBV individuals at FU: 34 (56.7%) showed HBV‐DNA suppression and 15 (25.0%) were HBV viraemic, while 12/89 (13.5%) remained without a FU test. Vaccinations induced anti‐HBs(+) in 137 of the retested 649 (21.1%) BL HBV‐naïve patients. Conclusion: HBV testing is well established among Viennese HIV+patients with HBV coinfection rates around 4%‐5%. HBV vaccinations are insufficiently implemented since anti‐HBs titres were detected in only 21.1% of HBV‐naive HIV(+) patients and new HBV infections occurred in previously vaccinated patients. HDV testing is not systematically performed despite up to 25% of HIV/HBV patients may show HDV coinfection. [ABSTRACT FROM AUTHOR]

Aims: Mass antigen testing programs have been challenged because of an alleged insufficient specificity, leading to a large number of false positives. The objective of this study is to derive a lower bound of the specificity of the SD Biosensor Standard Q Ag-Test in large scale practical use. Methods: Based on county data from the nationwide tests for SARS-CoV-2 in Slovakia between 31.10.–1.11. 2020 we calculate a lower confidence bound for the specificity. As positive test results were not systematically verified by PCR tests, we base the lower bound on a worst case assumption, assuming all positives to be false positives. Results: 3,625,332 persons from 79 counties were tested. The lowest positivity rate was observed in the county of Rožňava where 100 out of 34307 (0.29%) tests were positive. This implies a test specificity of at least 99.6% (97.5% one-sided lower confidence bound, adjusted for multiplicity). Conclusion: The obtained lower bound suggests a higher specificity compared to earlier studies in spite of the underlying worst case assumption and the application in a mass testing setting. The actual specificity is expected to exceed 99.6% if the prevalence in the respective regions was non-negligible at the time of testing. To our knowledge, this estimate constitutes the first bound obtained from large scale practical use of an antigen test. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) testing is generally available in most care centres, but it is rarely performed because clinicians' seldom suspect RSV to be the underlying pathogen in adults with respiratory disease. Here, we evaluate the impact of broad combined influenza/RSV testing on the clinical practice. Overall, 103 patients were tested positively for RSV. Our study indicates that positively tested patients were mostly of advanced age and suffered from chronic diseases. Mortality was significant in our cohort and higher in patients with advanced age. Further, we report a significant increase in detected RSV cases but also in detection rate. Together, these findings suggest that implementation of a combined influenza/RSV testing led to a significant increase in detection rate, supported clinicians establishing the correct diagnosis and allowed a safe and controlled handling of RSV patients. [ABSTRACT FROM AUTHOR]

To explore the epidemiology and clinical course of hepatitis A virus (HAV) infections at the Vienna General Hospital. We retrospectively identified patients who were tested positive for HAV-IgM at the Vienna General Hospital form Q1/2008 to Q3/2018. Our definition of severe HAV infection was AST and/or ALT > 5 × above the upper limit of normal (ULN); and liver dysfunction as (i) hepatic encephalopathy or ammonia > 100 μmol/L, (ii) coagulopathy with INR > 1.5, or (iii) jaundice with bilirubin > 5 mg/dL. A total of 578 HAV-IgM (+) were identified, including 31 (5.4%) and 38 (6.6%) without and with liver dysfunction, respectively. A proportional increase in severe HAV cases with and without liver dysfunction occurred in 2016/2017 with (21.5% (vs. 8.0% in the years before; p < 0.001). Thirty-seven (53.6%) patients with severe HAV were hospitalized, 6 (9%) required ICU support, and one patient received liver transplantation within 30 days. Patients with severe HAV and liver dysfunction were more often male (60.5 vs. 43.1%, p = 0.055) and younger (31.5 vs. 63 years, p < 0.001) as compared with other HAV-IgM (+) cases. The observed increase of severe HAV infections in Vienna in 2017 among young males, coincided with a multinational HAV outbreak among MSM. Our data suggests a higher likelihood of severe courses of hepatitis A in MSM. Vaccination against HAV should be recommended for risk groups. [ABSTRACT FROM AUTHOR]

Introduction: Immunoadsorption (IA) represents a therapeutic option for acute antibody-mediated rejection (ABMR) after kidney transplantation. The addition of membrane filtration (MF) to enhance elimination of macromolecular components that potentially contribute to rejection, such as key complement component C1q and alloreactive IgM, may be an effective strategy to further improve its therapeutic efficiency. Results: Here we present 4 consecutive patients with episodes of HLA donor-specific antibody-positive ABMR nonresponsive to cycles of 6–16 sessions of IA treatment. Rejection episodes were characterized by severe microvascular injury (high-grade microcirculation inflammation and/or signs of thrombotic microangiopathy) and evidence of intense complement activation in peritubular capillaries (diffuse C4d-positivity). IA combined with MF led to substantial morphologic improvement (follow-up biopsies: g + ptc and C4d scores ≤1) and stabilization of allograft function. Conclusions: Our findings provide evidence for an effect of combination of IA + MF in refractory early acute/active ABMR in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Summary: In kidney transplant recipients (KTRs), BK polyomavirus (BKPyV) replication may progress to polyomavirus‐associated nephropathy (PVAN). In this retrospective study, we assessed the chemokine CXCL10 in urine and blood samples consecutively acquired from 85 KTRs who displayed different stages of BKPyV replication and eventually developed PVAN. In parallel to progression toward PVAN, CXCL10 gradually increased in blood and urine, from baseline (prior to virus replication) to BKPyV DNAuria (median increase in blood: 42.15 pg/ml, P = 0.0156), from mere DNAuria to low‐ and high‐level BKPyV DNAemia (median increase: 52.60 and 87.26 pg/ml, P = 0.0010 and P = 0.0002, respectively) and peaked with histologically confirmed PVAN (median increase: 145.00 pg/ml, P < 0.0001). CXCL10 blood and urine levels significantly differed among KTRs with respect to simultaneous presence of human cytomegalovirus (P < 0.001) as well as in relation to the clinical severity of respective BKPyV DNAemia episodes (P = 0.0195). CXCL‐10 concentrations were particularly lower in KTRs in whom BKPyV DNAemia remained without clinical evidence for PVAN, as compared to individuals who displayed high decoy cell levels, decreased renal function and/or biopsy‐proven PVAN (median blood concentration: 266.97 vs. 426.42 pg/ml, P = 0.0282). In conclusion, in KTRs CXCL10 rises in parallel to BKPyV replication and correlates with the gradual development of PVAN. [ABSTRACT FROM AUTHOR]

• Archetype BKPyV predominates in the plasma and urine of patients with probable, presumptive or proven PVAN. • BKPyV reactivation in kidney transplant recipients increases viral load and leads to rearrangements within the viral genome. • Proven PVAN can develop without BKPyV rearrangements, although their frequency is highest among patients with proven PVAN. BKPyV is associated with polyomavirus-associated nephropathy (PVAN), a major cause of graft rejection in kidney transplant recipients (KTRs). Mutations occur in the transcriptional control region (TCR) of BKPyV, but whether they are required for the development of PVAN is not completely understood. To this end, we characterized BKPyV TCRs from KTRs to assess whether TCR mutations are associated with PVAN. We analyzed urine and plasma samples of fifteen KTRs with biopsy-confirmed PVAN, presumptive PVAN, or probable PVAN in order to explore the contents of the BKPyV virome. BKPyV TCRs were amplified and deep sequenced to characterize the viral strains. Alterations in block structures and transcription factor binding sites were investigated. The majority of sequences in both urine and plasma samples represented archetype BKPyV TCR. Minor populations harboring rearranged TCRs were detected in all patient groups. In one biopsy-confirmed PVAN patient rearranged TCRs predominated, and in another patient half of all reads represented rearranged sequences. Although archetype BKPyV predominated in most patients, highest proportions and highest numbers of rearranged strains were detected in association with PVAN. TCR mutations seem not necessary for the development of PVAN, but immunosuppression may allow increased viral replication giving rise to TCR variants with enhanced replication efficiency. [ABSTRACT FROM AUTHOR]

The impact of excess viral RNA on myocardial function and morphology in the setting of acute human immunodeficiency virus (HIV) infection remains unknown. In this study, 49 patients with acute HIV infection showed increased levels of N-terminal prohormone of brain natriuretic peptide, a surrogate of myocardial function, which decreased with viral suppression and normalization of systemic inflammation (79 pg/mL vs 28 pg/mL; P < .001). A comparable change was seen with levels of troponin T, a marker of morphologic myocardial damage (4.9 ng/L vs 1.5 ng/L; P < .001). In conclusion, we observed significant functional and morphological myocardial impairment during acute HIV infection, fueled by inflammatory activation and extensive viral replication, resulting in a reversible subclinical inflammatory cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background The toll-like receptor 2 (TLR2) is a significant component of innate immunity against cytomegalovirus (CMV) infection but information on the clinical significance of the single nucleotide polymorphism (SNP) (R753Q) is conflicting. Objectives The inconsistent observations of the immunological and clinical significance of the TLR2 R753Q polymorphism for CMV infection indicates the influence of confounders. Study design The presence of the TLR2 polymorphism was determined by a genotyping assay of 175 HTX patients and 281 healthy blood donors and evaluated in relation to selected virological and clinical parameters. Results Relative frequency of TLR2 polymorphism was similar in HTX patients and blood donors (homozygous wild-type, 94.3% vs. 94.0%; heterozygous, 5.1% vs. 5.7%; homozygous mutated, <1%). CMV viremia was detectable in 108 (61.7%) of HTX patients. The TLR2 polymorphism was neither associated with occurrence or level of CMV infection nor with survival, graft failure or rejection, or CMV serostatus of patient before transplantation. Nevertheless, CMV viremia occurred in 83.1% of R+/D+, 77.1% of R+/D-, and 64.3% of R-/D+ patients. Time of first CMV viremia was in R-/D+ patients later than in CMV-seropositive patients (median, 182 days versus 23 days; P < 0.001) corresponding to the duration of antiviral prophylaxis in R-/D+ patients. Conclusions The TLR2 R753Q polymorphism is extremely rare in the general population and HTX patients. Screening for this risk factor of CMV disease may not be cost-effective in contrast to testing for CMV viremia. [ABSTRACT FROM AUTHOR]

Background & Aims The severity of acute viral hepatitis, which may be caused by several distinct viruses, varies among individual patients. In rare cases, severe hepatic injury with sudden loss of liver function may occur, which is clinically indicated by the occurrence of coagulopathy or encephalopathy. As the molecular mechanisms of this liver injury are largely unknown, we investigated extracellular micro RNA (mi RNA) profiles in 54 patients acutely infected with one of four different hepatotropic viruses, in order to identify those mi RNAs which indicate severe viral hepatitis associated with coagulopathy. Methods First, the profile of mi RNAs was extensively analysed using a microarray-based approach in highly characterized 24 patients, matched in terms of sex, age and level of liver enzymes, as well as in three healthy controls. The cohort included samples from 18 patients with moderate and six individuals with severe hepatitis, indicated by abnormal prothrombin time and higher alanine aminotransferase and bilirubin levels. mi RNAs found to be upregulated in severe hepatitis were then quantified by real-time PCR in the expanded cohort of 54 patients. Results Comprehensive microarray-based mi RNA profiling identified upregulation of mir-106a, mir-122 and mir-197 in patients with severe acute viral hepatitis with coagulopathy, as compared to patients who did not develop coagulopathy. mir-106a, mir-122 and mir-197 were then proven to be significantly upregulated in patients with severe acute viral hepatitis by quantitative real-time PCR ( P < 0.01, Mann-Whitney U-test). Conclusions mir-106a, mir-122 and mir-197 could be potential markers for severe acute viral hepatitis associated with coagulopathy. [ABSTRACT FROM AUTHOR]

Despite increasing evidence in favor of prophylactic valganciclovir treatment in kidney transplant recipients for the prevention of cytomegalovirus (CMV) infection, the impact of preemptive vs. prophylactic treatment on long-term clinical outcomes is unclear. In this retrospective study, 187 kidney transplant recipients with serologic intermediate-risk constellation (recipient CMV IgG positive) received either preemptive or prophylactic treatment with valganciclovir. Patient survival (primary endpoint), graft survival, viremia rates, and other CMV-related outcomes were analyzed. Prophylactic therapy reduced the rates for CMV viremia during the first year (hazard ratio: 0.48, 95% confidence interval [CI] 0.30-0.75; p < 0.001). There was a trend for higher three-yr patient mortality in the prophylactic group (hazard ratio: 5.08, 95% CI 0.62-41.3; p = 0.091), and the rate of graft loss was not reduced (hazard ratio: 0.93, 95% CI 0.32-2.68; p = 0.894). Estimated glomerular filtration rate over three yr was on average 6.8 mL/min/1.73 m² lower in the prophylactic group (95% CI -11.68 to - 1.81 ; p = 0.007) using a multivariate random effects model but showed more improvement over time. Prophylactic valganciclovir treatment reduced the rate of CMV infections during the first year post-transplant but no effects of prophylactic treatment on patient and graft survival or kidney function over three yr were observed. [ABSTRACT FROM AUTHOR]

Background: Among HIV-1–infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1–infected subjects. Methods: Prospective, longitudinal study in 153 HIV-1–infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months. Results: Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results. Conclusions: While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results. [ABSTRACT FROM AUTHOR]

Background Among HIV-1–infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1–infected subjects. Methods Prospective, longitudinal study in 153 HIV-1–infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months. Results Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMVQFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results. Conclusions While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMVQFT results. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the therapeutic potential of telaprevir (TPV)/boceprevir (BOC)-based triple-therapy in a complete cohort of HIV/chronic hepatitis C co-infected patients (HIV/HCV). Moreover, a case series of four HIV/HCV genotype (HCV-GT)1 patients with rapid virologic response (RVR), who received only 28 weeks of BOC-based triple-therapy (BOCW28), was reported. 290/440 HIV-positive patients with positive HCV serology had at least one visit during the past 2 years, 142/290 had target detectable HCV-RNA with 64% (82/142) carrying HCV-GT1. While 18 HIV/HCV-GT1 displayed contraindications, 45% (64/142) of HIV/HCV were eligible for triple-therapy. Insufficiently controlled HIV-infection despite combined antiretroviral therapy (cART) (HIV-RNA <50 copies/mL: 73% vs. 22%; p<0.001) and liver cirrhosis (31% vs. 8%; p=0.025) were overrepresented among patients with contraindications for triple-therapy. Low treatment uptake rates (39% (25/64)) during the first 2 years of triple-therapy availability suggest that its benefit in HIV/HCV co-infected patients might fall short of expectations. Modification of cART or TPV dose adjustment would have been necessary in 61% and 84% of HIV/HCV-GT1 on cART eligible for triple-therapy using TPV and BOC, respectively, suggesting that drug-drug interactions with cART complicate management in the majority of patients. All four BOCW28 patients achieved a sustained virologic response. Prospective studies are necessary to validate our observations on the shortening of treatment duration in HIV/HCV-GT1 with RVR. [ABSTRACT FROM AUTHOR]

Background: Nucleos(t)ide analog (NA) treatment for hepatitis B virus (HBV) infection may improve clinically significant portal hypertension (CSPH). Data on hepatic venous pressure gradient (HVPG) and non-invasive tests (NITs) for risk re-stratification in virally suppressed HBV-infected patients with pre-treatment CSPH are limited. Methods: We retrospectively included patients with long-term (>12 months) suppression of HBV replication and pre-treatment CSPH (i.e., varices, collaterals on cross-sectional imaging, or ascites). Patients were monitored by on-treatment liver stiffness measurement (LSM) and HVPG assessment. The primary outcome was (further) hepatic decompensation (including liver-related mortality). Results: Forty-two patients (n = 12 (28.6%) with previous decompensation, HBeAg-negative: n = 36 (85.7%)) were included and followed for 2.1 (0.6; 5.3) years. The median HVPG (available in n = 17) was 15 (10; 22) mmHg and the median LSM 22.5 (12.5; 41.0) kPa. LSM correlated strongly with HVPG (Spearman's ρ: 0.725, p < 0.001) and moderately with the model for end-stage liver disease (MELD) score (ρ: 0.459, p = 0.002). LSM, MELD and albumin levels had good prognostic value for decompensation (area under the receiver operated characteristics curve (AUROC) >0.850 for all). LSM predicted (further) decompensation in competing risk regression (subdistribution hazard ratio (SHR): 1.05 (95% confidence interval(CI) 1.03–1.06); p < 0.001), even after adjusting for other factors. An LSM cut-off at 25kPa accurately stratified patients into a low-risk (n = 23, zero events during follow-up) and a high-risk (n = 19; n = 12 (63.2%) developed events during follow-up) group. Conclusions: Patients with HBV-induced CSPH who achieved long-term viral suppression were protected from decompensation, if LSM was <25 kPa. LSM ≥ 25 kPa indicates a persisting risk for decompensation, despite long-term HBV suppression. [ABSTRACT FROM AUTHOR]

Highlights from the article: P203 Late antibody-mediated rejection (ABMR) after kidney transplantation - Role of the eGFR slope within the first year after biopsy as a surrogate endpoint predicting graft failure There is currently no effective, evidence-proven treatment for late ABMR. Median eGFR at the time of biopsy was 42 mL/min/1.73 m SP 2 sp (IQR: 39-45) and the median eGFR slope (first 12 months after ABMR diagnosis) was -4.4 mL/min/1.73 m SP 2 sp .

Chronic lymphocytic leukemia (CLL) is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV) disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs) encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200). CMV-DNA was detected in 3% (6/200) of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03) and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001). Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06) and mean decay values differed significantly from those of total IgG (p=0.034). Boosts of CMV-specific antibody levels were observed in 49% (22/45) of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively). VZV-specific IgG even became undetectable in 18% (9/50) of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered apparently by other CMV antigens than pUL32, like glycoprotein B. [ABSTRACT FROM AUTHOR]