The non‐pathogenic and ubiquitous Torque Teno virus (TTV) is associated with immunosuppression in solid organ transplant recipients. Studies in kidney transplant patients proposed TTV quantification for risk stratification of graft rejection and infection. In this prospective trial (DRKS00012335) 386 consecutive kidney transplant recipients were subjected to longitudinal per‐protocol monitoring of plasma TTV load by PCR for 12 months post‐transplantation. TTV load peaked at the end of month 3 post‐transplantation and reached steady state thereafter. TTV load after the end of month 3 was analyzed in the context of subsequent rejection diagnosed by indication biopsy and infection within the first year post‐transplantation, respectively. Each log increase in TTV load decreased the odds for rejection by 22% (OR 0.78, 95%CI 0.62‐0.97; P=.027) and increased the odds for infection by 11% (OR 1.11, 95%CI 1.06‐1.15; P<.001). TTV was quantified at a median of 14 days before rejection was diagnosed and 27 days before onset of infection, respectively. We defined a TTV load between 1x10⁶ and 1x10⁸ copies/mL as optimal range to minimize the risk for rejection and infection. These data support the initiation of an interventional trial assessing the efficacy of TTV‐guided immunosuppression to reduce infection and graft rejection in kidney transplant recipients.

Torque Teno virus (TTV) is nonpathogenic, highly prevalent, and reflects the immune status of its host. Thus, TTV plasma load was suggested for the guidance of immunosuppression post solid organ transplantation. The present study was designed to determine the kinetics of TTV following changes in calcineurin inhibitor (CNI) dose. A total of 48 adult recipients of a kidney graft transplanted at the Medical University of Vienna between 2018 and 2019 with isolated changes in CNI dose were selected from the prospective TTV‐POET trial. TTV plasma load was quantified by in‐house PCR. At Day 30 following CNI dose adaptation (median 33% of daily dose) no changes in TTV load were noted. However, at Day 60, following CNI dose reduction a lower TTV load of 6.4 log₁₀ c/mL (median; interquartile range [IQR] 4.9–8.1) compared with the baseline of 7.1 log₁₀ c/mL (IQR 5.3–8.9) was noted (p = 0.001); there was also a trend toward a higher TTV load following CNI increase (6.6 log₁₀ c/mL, IQR 4.1–9.7 vs. 5.2 log₁₀ c/mL, IQR 4.5–6.8; p = 0.09). The data suggested that TTV load changes become noticeable only 2 months after CNI dose adaptation, which might be the ideal time point for TTV load monitoring.

Background: In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies have become available quickly. However, the clinical performance of many of them is still insufficiently described. Therefore we compared three commercial, CE-marked, SARS-CoV-2 antibody assays side by side. Methods: We included a total of 1,154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients (≥14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. Results: All three assays presented with high specificities: 99.2% (98.6-99.7) for Abbott, 99.7% (99.2-100.0) for Roche, and 98.3% (97.3-98.9) for DiaSorin. In contrast to the manufacturers’ specifications, sensitivities only ranged from 83.1% to 89.2%. Although the three methods were in good agreement (Cohen’s Kappa 0.71-0.87), McNemar’s test revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictability at 1% seroprevalence: 52.3% (36.2-67.9), 77.6% (52.8-91.5), and 32.6% (23.6-43.1) for Abbott, Roche, and DiaSorin, respectively. Conclusion: We find diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictability of these tests.

This study aimed to determine the specific cytokine profile in peripheral blood during the early onset of COVID-19 infection. This was a cross-sectional exploratory, single center study. A total of 55 plasma samples were studied. Serum samples of adults showing symptoms of COVID-19 infection who were tested positive for SARS-CoV-2 infection (CoV+, n=18) at the COVID-19 outpatient clinic of the Medical University of Vienna were screened for immune activation markers by Luminex technology. Additionally, age and gender-matched serum samples of patients displaying COVID-19 associated symptoms, but tested negative for SARS-CoV-2 (CoV-, n=16) as well as healthy controls (HC, n=21) were analyzed. COVID-19 positive (CoV+) patients showed a specific upregulation of BLC (141; 74-189 pg/mL), SCD30 (273; 207-576 pg/mL), MCP-2 (18; 12-30 pg/mL) and IP-10 (37; 23-96 pg/mL), compared to patients with COVID19-like symptoms but negative PCR test (CoV-), BLC (61; 22-100 pg/mL), sCD30L (161; 120-210 pg/mL), MCP-2 (8; 5-12 pg/mL) and IP-10 (9; 6-12 pg/mL) and healthy controls (HC) (BLC 22; 11-36 pg/mL, sCD30 74; 39-108 pg/mL, MCP-2 6; 3-9. pg/mL, IP-10 = 8; 5-13). The markers APRIL, sIL-2R, IL7, MIF, MIP-1b, SCF, SDF-1a, sTNF-RII were elevated in both CoV+ and CoV- patient groups compared to healthy controls. HGF, MDC and VEGF-A were elevated in CoV- but not CoV+ compared to healthy controls. BLC, sCD30, MCP-2 and IP-10 are specifically induced during early stages of COVID-19 infection and might constitute attractive targets for early diagnosis and treatment of this disease.

With global demand for SARS-CoV-2 testing ever rising, shortages in commercially available viral transport media pose a serious problem for laboratories and health care providers. For reliable diagnosis of SARS-CoV-2 and other respiratory viruses, executed by Real-time PCR, the quality of respiratory specimens, predominantly determined by transport and storage conditions, is crucial. Therefore, our aim was to explore the reliability of minimal transport media, comprising saline or the CDC recommended Viral Transport Media (HBSS VTM), for the diagnosis of SARS-CoV-2 and other respiratory viruses (influenza A, respiratory syncytial virus, adenovirus, rhinovirus and human metapneumovirus) compared to commercial products, such as the Universal Transport Media (UTM). We question the assumptions, that the choice of medium and temperature for storage and transport affect the accuracy of viral detection by RT-PCR. Both alternatives to the commercial transport medium (UTM), HBSS VTM or saline, allow adequate detection of SARS-CoV-2 and other respiratory viruses, regardless of storage temperatures up to 28 °C and storage times up to 28 days. Our study revealed the high resilience of SARS-CoV-2 and other respiratory viruses, enabling proper detection in clinical specimens even after long-time storage at high temperatures, independent of the transport medium’s composition.

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.