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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., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval (N°20-079-VK) was provided by the Ethics Committee of the City of Vienna. Due to the retrospective nature of the study, the Ethics Committee of the City of Vienna waived the need of obtaining informed consent. The study complies with the Declaration of Helsinki and STROBE guidelines. Consent for publication: Informed consent (and therefore also consent for publication) was waived by the Ethics Committee. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Robert Strassl reports financial support was provided by Austrian Science Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination is severely impaired in patients on maintenance immunosuppression after kidney transplantation., Methods: We conducted a prospective cohort study of 194 kidney transplant recipients (KTR) who exhibited no response to SARS-CoV-2 vaccinations (i.e., SARS-CoV-2 spike protein antibodies ≤264 U/mL) and had no prior documented infection. Patients received 300 mg of cilgavimab/tixagevimab as SARS-CoV-2 pre-exposure prophylaxis (PrEP) between March 4, 2022, and May 3, 2022 and were contrasted to a matched cohort of 186 KTRs also without immunization again defined as SARS-CoV-2 spike protein antibodies ≤264 U/mL and no documented prior infection. The primary outcome was the serum kinetics of cilgavimab/tixagevimab, the secondary endpoints were time to SARS-CoV-2 breakthrough infection, severity of disease and variant specific live viral in vitro neutralization tests of patient sera., Findings: Longitudinal serum level monitoring showed a half-life of 91 days for both antibodies (95% CI 86-95 days for cilgavimab and 85-96 days for tixagevimab) in KTRs. In vitro neutralization tests showed effectiveness against the BA.2 omicron subvariant but not BA.5. The cumulative incidence of SARS-CoV-2 infections until May 15, 2022, (BA.2 dominance) was 15/194 vs 36/186 in the PrEP and control group respectively (OR = 0.35, 95% CI 0.18-0.66) but was not different thereafter (BA.4/5 dominance). The number of severe infections during the BA.2 period was lower in the prophylaxis than in the control group (OR = 0.37, 95% CI 0.17-0.79)., Interpretation: This study showed that SARS-CoV-2 PrEP with cilgavimab/tixagevimab demonstrated clinical effectiveness against variants that are neutralised (BA.2) but not against BA.4/5., Funding: This study was funded by the Medical University of Vienna and an unrestricted grant from AstraZeneca (ESR-21-21585)., Competing Interests: Declaration of interests “The authors declare no competing interests for this manuscript”, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the 'sensitivity improved two-test' or 'SIT²' algorithm., Methods: SIT² involves confirmatory retesting of samples with results falling in a predefined retesting zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT² to single tests and orthogonal testing (OTA) in an Austrian cohort (1117 negative, 64 post-COVID-positive samples) and validated the algorithm in an independent British cohort (976 negatives and 536 positives)., Results: The specificity of SIT² was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT² when compared with single tests or OTA. SIT² allowed correct identification of infected individuals even when a live virus neutralisation assay could not detect antibodies. Compared with single testing or OTA, SIT² significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence., Conclusion: For SARS-CoV-2 serology, SIT² proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases., Competing Interests: Competing interests: NP-N received a travel grant from DiaSorin. DWE reports lecture fees from Gilead outside the submitted work. OCB reports grants from GSK, grants from Menarini, grants from Boehringer Ingelheim, grants from Astra, grants from MSD, grants from Pfizer, and grants from Chiesi, outside the submitted work. SH does receive unrestricted research grants (GSK, Boehringer, Menarini, Chiesi, Astra Zeneca, MSD, Novartis, Air Liquide, Vivisol, Pfizer, TEVA) for the Ludwig Boltzmann Institute of COPD and Respiratory Epidemiology, and is on advisory boards for G. SK, Boehringer Ingelheim, Novartis, Menarini, Chiesi, Astra Zeneca, MSD, Roche, Abbvie, Takeda and TEVA for respiratory oncology and COPD. PQ is an advisory board member for Roche Austria and reports personal fees from Takeda outside the submitted work. The Dept. of Laboratory Medicine (Head: OWF) received compensations for advertisement on scientific symposia from Roche, DiaSorin, and Abbott and holds a grant for evaluating an in-vitro diagnostic device from Roche. CJB is a Board Member of Technoclone. HH receives compensations for biobank services from Glock Health Science and Research and BlueSky immunotherapies., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Post acute sequelae of SARS-CoV-2 infection are defined by persistence or re-occurrence of symptoms six to 12 weeks after SARS-CoV-2 infections., Methods: Twice vaccinated hospital employees after mild to moderate post-vaccination SARS-CoV-2 infection completed a questionnaire on the incidence of general, respiratory, neuropsychiatric, dermatological and gastrointestinal symptoms, experienced during their acute infection and eight weeks after recovery. Post acute sequelae of SARS-CoV-2 infection were analysed in relation to socio-demographic-, health-, virus- and acute infection-related characteristics., Results: 73 participants, 25 women and 48 men with a mean age of 40.9 years, with a post-vaccination SARS-CoV-2 infection completed the survey. Out of these 93 % reported at least one symptom at time of initial SARS-CoV-2 infection, 31.5 %, predominantly women, reported post acute sequelae at least eight weeks after the acute infection stage. Fatigue, dysgeusia and dysosmia, headache or difficulty concentrating and shortness of breath during acute infection, BMI> 25 and pre-existing pulmonary disorders were associated with post acute sequelae of SARS-CoV-2 infection. Participants with initially more than five symptoms were four times more likely to report post acute sequelae., Conclusion: It is suggested that the multiplicity of symptoms during acute SARS-CoV-2 infections increases the risk for post acute symptoms., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The severity of COVID-19 is associated with individual genetic host factors. Among these, genetic polymorphisms affecting natural killer (NK) cell responses, as variations in the HLA-E- (HLA-E*0101/0103), FcγRIIIa- (FcγRIIIa-158-F/V), and NKG2C- (KLRC2 wt/del ) receptor, were associated with severe COVID-19. Recently, the rs9916629-C/T genetic polymorphism was identified that indirectly shape the human NK cell repertoire towards highly pro-inflammatory CD56 bright NK cells. We investigated whether the rs9916629-C/T variants alone and in comparison to the other risk factors are associated with a fatal course of COVID-19. We included 1042 hospitalized surviving and 159 nonsurviving COVID-19 patients as well as 1000 healthy controls. rs9916629-C/T variants were genotyped by TaqMan assays and were compared between the groups. The patients' age, comorbidities, HLA-E*0101/0103, FcγRIIIa-158-F/V, and KLRC2 wt/del variants were also determined. The presence of the rs9916629-C allele was a risk factor for severe and fatal COVID-19 (p < 0.0001), independent of the patients' age or comorbidities. Fatal COVID-19 was more frequent in younger patients (<69.85 years) carrying the FcγRIIIa-158-V/V (p < 0.006) and in older patients expressing the KLRC2 del variant (p < 0.003). Thus, patients with the rs9916629-C allele have a significantly increased risk for fatal COVID-19 and identification of the genetic variants may be used as prognostic marker for hospitalized COVID-19 patients., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Brain tumors are the most common solid malignancies and the leading cause of cancer-related mortality in children. While numerous studies report on viral infections in children with hematologic malignancies and solid organ transplantation, epidemiologic data on the incidence and outcome of viral infections in pediatric patients with brain tumors treated with targeted therapies are still lacking., Objectives/study Design: We retrospectively reviewed all children with brain tumors receiving targeted therapies in a primary or recurrent setting at the Medical University of Vienna from 2006 to 2021. Demographic variables, quantitative and qualitative parameters of possible infections, and treatment outcomes were recorded., Results: In our cohort (n = 117), 36% of the patients developed at least one PCR-proven viral infection. Respiratory and gastrointestinal tract infections were most common, with 31% and 25%, respectively. Central nervous system (CNS) infections occurred in approximately 10%, with an almost equal distribution of varicella-zoster virus, John Cunningham virus (JCV), and enterovirus. Two patients tested PCR-positive for SARS-CoV-2 infection, with one virus-related death caused by a SARS-CoV-2-related acute respiratory distress syndrome. Patients receiving bevacizumab or mTOR inhibitors seem to have a greater susceptibility to viral infections., Conclusion: Pediatric patients with brain tumors receiving targeted therapies have a higher risk of viral infections when compared to children receiving conventional chemotherapy or the general population, and life-threatening infections can occur. Fast detection and upfront treatment are paramount to prevent life-threatening infections in immunocompromised children suffering from brain tumors receiving targeted therapies., (© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background and Aims: Cholestasis is associated with disease severity and worse outcome in COVID-19. Cases of secondary sclerosing cholangitis (SSC) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been described., Approach and Results: Hospitalized patients with COVID-19 between 03/2020 and 07/2021 were included. Patients were stratified as having (i) no chronic liver disease (CLD), (ii) non-advanced CLD (non-ACLD), or (iii) advanced CLD (ACLD). Patients with CLD and non-COVID-19 pneumonia were matched to patients with CLD and COVID-19 as a control cohort. Liver chemistries before (Pre) and at first, second, and third blood withdrawal after SARS-CoV-2 infection (T1-T3) and at last available time point (last) were recorded. A total of 496 patients were included. In total, 13.1% (n = 65) had CLD (non-ACLD: 70.8%; ACLD: 29.2%); the predominant etiology was NAFLD/NASH (60.0%). COVID-19-related liver injury was more common among patients with CLD (24.6% vs. 10.6%; p = 0.001). After SARS-CoV-2 infection, patients with CLD exhibited progressive cholestasis with persistently increasing levels of alkaline phosphatase (Pre: 91.0 vs. T1: 121.0 vs. last: 175.0 U/L; p < 0.001) and gamma-glutamyl transferase (Pre: 95.0 vs. T1: 135.0 vs. last: 202.0 U/L; p = 0.001). A total of 23.1% of patients with CLD (n = 15/65) developed cholestatic liver failure (cholestasis plus bilirubin ≥6 mg/dl) during COVID-19, and 15.4% of patients (n = 10/65) developed SSC. SSC was significantly more frequent among patients with CLD and COVID-19 than in patients with CLD and non-COVID-19 pneumonia (p = 0.040). COVID-19-associated SSC occurred predominantly in patients with NAFLD/NASH and metabolic risk factors. A total of 26.3% (n = 5/19) of patients with ACLD experienced hepatic decompensation after SARS-CoV-2 infection., Conclusions: About 20% of patients with CLD develop progressive cholestasis after SARS-CoV-2 infection. Patients with NAFLD/NASH and metabolic risk factors are at particular risk for developing cholestatic liver failure and/or SSC after COVID-19., (© 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

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., (© 2022 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Background: Coronavirus disease of 2019 (COVID-19) has affected liver disease management. The impact of the COVID-19 pandemic on the Austrian orthotopic liver transplantation (OLT) programs, however, has not been systematically investigated., Methods: All patients listed for OLT in Austria during 2020-2021 were studied. Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, vaccinations, infections, mortality and the overall number of OLTs (vs. pre-COVID-19: 2015-2019) were analyzed., Results: Overall, 490 patients (median age: 58.0 years, 70.4% men, hepatocellular carcinoma: 27.3%) were listed for OLT in Austria in 2020-2021. Alcohol-related cirrhosis (35.3%), cholestatic (16.7%) and viral liver disease (13.9%) were the main etiologies. Of the patients 61.2% underwent OLT and 8.8% died while on the waiting list. The number of OLTs performed during COVID-19 (2020: n = 150; 2021: n = 150) remained unchanged compared to pre-COVID-19 (median: n = 152). Among waiting list patients, 7.7% (n = 31/401) were diagnosed with COVID-19 and 7 (22.6%) of these patients died. By the end of 2021, 45.1% (n = 176/390; 82.8% mRNA vaccinations) and 28.8% (105/365) of patients received 2 and 3 SARS-CoV‑2 vaccinations, respectively. After two SARS-CoV‑2 vaccinations, antibodies more often remained undetectable in patients vaccinated post-OLT (25.6% vs. 6.5% in patients vaccinated pre-OLT; p = 0.034). Patients with three vaccinations after OLT had lower antibody titers than patients vaccinated pre-OLT (post-OLT: 513.5, IQR 44.4-2500.0 vs. pre-OLT: 2500.0, IQR 1462.0-2500.0 BAU/mL; p = 0.020)., Conclusion: The number of OLTs in Austria remained unchanged during COVID-19. SARS-CoV‑2 infections were rare but associated with high mortality in patients on the Austrian OLT waiting lists. SARS-CoV‑2 vaccination rates at the end of 2021 were suboptimal, while serological response was better in patients vaccinated pre-OLT vs. post-OLT., (© 2022. The Author(s).)

SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the "alternative" (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1-7. Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I-II) and alt-RAS (angiotensins 1-7 and 1-5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n = 76; non-severe: n = 83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1-7. Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (angiotensin I: 86 versus 30 pmol/L, p < 0.01; angiotensin II: 114 versus 58 pmol/L, p < 0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor (angiotensin I: 40 versus 31 pmol/L, p = 0.251; angiotensin II: 76 versus 99 pmol/L, p = 0.833). ALT-S in severe COVID-19 increased with time (days 1-6: 0.12; days 11-16: 0.22) and correlated with ACE2 concentration (r = 0.831). ACE-S was lower in severe versus non-severe COVID-19 (1.6 versus 2.6; p < 0.001), but ACE concentrations were similar between groups and correlated weakly with ACE-S (r = 0.232). ACE2 and ACE-S trajectories in severe COVID-19, however, did not differ between survivors and non-survivors. Overall RAS alteration in severe COVID-19 resembled severity of disease-matched patients with influenza. In mixed linear models, renin activity most strongly predicted angiotensin II and 1-7 levels. ACE2 also predicted angiotensin 1-7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S. ACE2 and ACE-S trajectories in severe COVID-19 did not differ between survivors and non-survivors. In conclusion, angiotensin II was elevated in severe COVID-19 but was markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels., (© 2022. The Author(s).)

Background: The SARS-CoV-2 pandemic increased mortality and morbidity among immunocompromised populations. Vaccination is the most important preventive measure, however, its effectiveness among patients depending on maintenance immunoglobulin G (IgG) apheresis to control autoimmune disease activity is unknown. We aimed to examine the humoral immune response after mRNA-1273 Moderna ® vaccination in immunoapheresis patients., Methods: We prospectively monitored SARS-CoV-2 IgG spike (S) protein antibody levels before and after each IgG ( exposure ) or lipid (LDL) apheresis ( controls ) over 12 weeks and once after 24 weeks. Primary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels from vaccination until week 12, secondary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels by apheresis treatments across groups., Results: We included 6 IgG and 18 LDL apheresis patients. After 12 weeks the median SARS-CoV-2 IgG S antibody level was 115 (IQR: 0.74, 258) in the IgG and 1216 (IQR: 788, 2178) in the LDL group (p=0.03). Median SARS-CoV-2 IgG S antibody reduction by apheresis was 76.4 vs. 23.7% in the IgG and LDL group (p=0.04). The average post- vs. pre -treatment SARS-CoV-2 IgG S antibody rebound in the IgG group vs. the LDL group was 46.1 and 6.44%/week from prior until week 12 visit., Conclusions: IgG apheresis patients had lower SARS-CoV-2 IgG S antibody levels compared to LDL apheresis patients, but recovered appropriately between treatment sessions. We believe that IgG apheresis itself probably has less effect on maintaining the immune response compared to concomitant immunosuppressive drugs. Immunization is recommended independent of apheresis treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gaggl, Aschauer, Aigner, Bond, Vychytil, Strassl, Wagner, Sunder-Plassmann and Schmidt.)

Respiratory syncytial virus (RSV) is a well-known pathogen in paediatric patients. However, it also causes substantial morbidity and mortality in adults, posing a major healthcare problem. We present a patient with chronic pulmonary conditions and an acute RSV infection, thus leading to cardiac arrest (CA). We speculate that RSV as the causative agent for CA should be considered in post-resuscitation care. From a wider public health perspective, immuno-naivety for RSV caused by the coronavirus disease 2019 pandemic may induce a severe rise in cases, morbidity, and mortality in the future.

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., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Objectives: 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., Methods: 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., Results: All participants could detect a highly positive patient-derived sample (>10 6 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., Conclusions: 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., (© 2022 Christoph Buchta et al., published by De Gruyter, Berlin/Boston.)

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., (© 2022. The Author(s).)

Objectives: 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., Methods: 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)., Results: 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)., Conclusions: BNT162b2 and ChAdOx1-S are both effective in preventing breakthrough infections; however, it seems important, that all recommended vaccine doses are administered., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The objective of our study was to evaluate the sensitivity and specificity of rapid antigen detection tests versus those of reverse transcriptase PCR (RT-PCR) using oral, anterior nasal, and nasopharyngeal swabs. The underlying prospective, diagnostic case-control-type accuracy study included 87 hospitalized and nonhospitalized participants in a positive and a negative sample cohort between 16 March and 14 May 2021 in two hospitals in Vienna. SARS-CoV-2 infection status was confirmed by RT-PCR. Participants self-performed one oral and one anterior nasal swab for the rapid antigen test, immediately followed by two nasopharyngeal swabs for the rapid antigen test and RT-PCR by the investigator. Test results were read after 15 min, and participants completed a questionnaire in the meantime. Test parameters were calculated based on the evaluation of 87 participants. The overall sensitivity of rapid antigen detection tests versus that of RT-PCR with oral, anterior nasal, and nasopharyngeal samples was 18.18% (95% confidence interval [CI] 8.19% to 32.71%), 63.04% (95% CI 47.55% to 76.79%), and 73.33% (95% CI 58.06% to 85.4%), respectively. All sampling methods had a test specificity of 100% regardless of the cycle threshold ( C T ) value. Rapid antigen detection tests using self-collected anterior nasal swabs proved to be as sensitive as and more tolerable than professionally collected nasopharyngeal swabs for C T values up to 30 determined by RT-PCR. This finding illustrates the reliability of tests obtained by adequate self-collected anterior nasal specimen. Sensitivity was dependent upon the C T value for each sampling method. While the main advantage of rapid antigen detection tests is the immediate availability of results, PCR should be preferred in crucial settings wherever possible. IMPORTANCE Rapid antigen detection devices for SARS-CoV-2 represent a valuable tool for monitoring the spread of infection. However, the reliability of the tests depends largely on the test performance and the respective sampling method. Nasopharyngeal swabs mark the gold standard for sample collection in suspected respiratory tract infections but are unsuitable for widespread application, as they must be performed by medically trained personnel. With the underlying study, the head-to-head test performance and the usability of self-collected samples for SARS-CoV-2 detection using rapid antigen detection devices were evaluated. The results confirm similar sensitivity of self-collected anterior nasal swabs to that of professionally collected nasopharyngeal swabs for patients with a C T of < 30 determined by RT-PCR.

Importance: Fewer than 50% of kidney transplant recipients (KTRs) develop antibodies against the SARS-CoV-2 spike protein after 2 doses of an mRNA vaccine. Preliminary data suggest that a heterologous vaccination, combining mRNA and viral vector vaccines, may increase immunogenicity., Objective: To assess the effectiveness of a third dose of an mRNA vs a vector vaccine in KTRs who did not have antibodies against the SARS-CoV-2 spike protein after 2 doses of an mRNA vaccine., Design, Setting, and Participants: This was a single center, single-blinded, 1:1 randomized clinical trial of a third dose of vaccine against SARS-CoV-2, conducted from June 15 to August 16, 2021, in 201 KTRs who had not developed SARS-CoV-2 spike protein antibodies after 2 doses of an mRNA vaccine. Data analyses were performed from August 17 to August 31, 2021., Interventions: mRNA (BNT162b2 or mRNA-1273) or vector (Ad26COVS1) as a third dose of a SARS-CoV-2 vaccine., Main Outcomes and Measures: The primary study end point was seroconversion after 4 weeks (29-42 days) following the third vaccine dose. Secondary end points included neutralizing antibodies and T-cell response assessed by interferon-γ release assays (IGRA). In addition, the association of patient characteristics and vaccine response was assessed using logistic regression, and the reactogenicity of the vaccines was compared., Results: Among the study population of 197 kidney transplant recipients (mean [SD] age, 61.2 [12.4] years; 82 [42%] women), 39% developed SARS-CoV-2 antibodies after the third vaccine. There was no statistically significant difference between groups, with an antibody response rate of 35% and 42% for the mRNA and vector vaccines, respectively. Only 22% of seroconverted patients had neutralizing antibodies. Similarly, T-cell response assessed by IGRA was low with only 17 patients showing a positive response after the third vaccination. Receiving nontriple immunosuppression (odds ratio [OR], 3.59; 95% CI, 1.33-10.75), longer time after kidney transplant (OR, 1.44; 95% CI, 1.15-1.83, per doubling of years), and torque teno virus plasma levels (OR, 0.92; 95% CI, 0.88-0.96, per doubling of levels) were associated with vaccine response. The third dose of an mRNA vaccine was associated with a higher frequency of local pain at the injection site compared with the vector vaccine, while systemic symptoms were comparable between groups., Conclusions and Relevance: This randomized clinical trial found that 39% of KTRs without an immune response against SARS-CoV-2 after 2 doses of an mRNA vaccine developed antibodies against the SARS-CoV-2 spike protein 4 weeks after a third dose of an mRNA or a vector vaccine. The heterologous vaccination strategy with a vector-based vaccine was well tolerated and safe but not significantly better than the homologous mRNA-based strategy., Trial Registration: EudraCT Identifier: 2021-002927-39.

Importance: To our knowledge, little is known about antibody development after SARS-CoV-2 vaccination in immunocompromised individuals, such as patients with cancer., Objective: To determine whether hematooncological patients develop anti-SARS-CoV-2 antibodies after vaccination., Design, Setting, and Participants: This retrospective cohort study included 2 independent cohorts of patients who were treated for hematological and solid malignant tumors between October 2020 and May 2021, comprising 901 samples from 595 patients and 58 health care workers (HCWs). Serum samples were collected from patients who were treated at an academic center and a community hospital in a rural area and a control group of HCWs, all of whom received SARS-CoV-2 vaccination., Main Outcomes and Measures: Total anti-SARS-CoV-2 nucleocapsid (anti-NC) and antispike protein (anti-S) antibodies were measured retrospectively., Results: In total, 595 patients (320 women [53.8%] and 275 men [46.2%]; median [range] age, 67 [19-96] years) and 58 HCWs (40 women [69.0%] and 18 men [31.0%]; median [range] age, 42 [24-60] years) were included. Previous SARS-CoV-2 infection was documented in 43 of 595 (7.2%), while anti-NC antibodies that suggested previous infections were observed in 49 of 573 evaluable patients (8.6%). In both cohorts, anti-S antibody levels were higher in fully vaccinated patients compared with patients who received 1 dose. After the first vaccination, patients with hematological cancer who received B cell-targeting agents had lower anti-S levels (median, 1.6 AU/mL; range: 0-17 244 AU/mL) than patients who received other therapies (median, 191.6 AU/mL; range, 0-40 000; P < .001) or patients with solid tumors (median, 246.4 AU/mL; range, 0-40 000 AU/mL; P < .001). Anti-S levels after the first vaccination differed according to ongoing antineoplastic treatment modalities, with the lowest median levels in patients who received chemotherapy alone (157.7 AU/mL; range, 0-40 000 AU/mL) or in combination with immunotherapy (118.7 AU/mL; range, 14.1-38 727 AU/mL) and the highest levels in patients with no ongoing antineoplastic treatment (median, 634.3 AU/mL; range, 0-40 000 AU/mL; P = .01). Antibody levels after full immunization were higher in HCWs (median, 2500 U/mL; range, 485-2500 U/mL) than in patients with cancer (median, 117.0 U/mL; range, 0-2500 U/mL; P < .001)., Conclusions and Relevance: In this cohort study of patients with hematooncological diseases and a control group of HCWs, anti-SARS-CoV-2 antibodies after vaccination could be detected in patients with cancer. Lower antibody levels compared with HCWs and differences in seroconversion in specific subgroups underscore the need for further studies on SARS-CoV-2 vaccination in patients with hematooncological disease.

Background: Dialysis patients are at high risk for a severe clinical course after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Safety and early immune responses after mRNA-based vaccination have been reported mostly in patients on hemodialysis (HD), whereas reports of peritoneal dialysis (PD) patients remain rare., Methods: In this retrospective observational study, 39 PD patients had received two doses of the mRNA-1273 Moderna ® vaccine. We analyzed SARS-CoV-2 Spike (S) antibody titers 4 weeks after each dose of mRNA-1273 and report local and systemic side effects in PD patients that occurred within one week after each mRNA-1273 dose. Using a quantile regression model we examined factors that might influence SARS-CoV-2 S antibody levels in PD patients., Results: Four weeks after the first dose of mRNA-1273 vaccine 33 of 39 (84.6%) PD patients seroconverted and presented with 6.62 U/mL (median; IQR 1.57-22.5) anti-SARS-CoV-2 S antibody titers. After the second dose, 38 of 39 (97.4%) PD patients developed anti-SARS-CoV-2 S antibodies and titers increased significantly (median 968 U/mL; IQR 422.5-2500). Pain at the injection site was the most common local adverse event (AE) (71%). Systemic AEs occurring after the first dose were mostly fatigue (33%) and headache (20%). No severe systemic AEs were reported after the first injection. After the second dose the incidence and the severity of the systemic AEs increased. The most common systemic AEs were: fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (13%). Lower Davies Comorbidity Score (p=0.04) and shorter dialysis vintage (p=0.017) were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.53x10 -05 )., Conclusions: Peritoneal dialysis patients in this cohort had a high seroconversion rate of 97.4%, showed high antibody titers after full vaccination and tolerated the anti-SARS-CoV-2 mRNA-1273 vaccine well without serious adverse events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Beilhack, Monteforte, Frommlet, Gaggl, Strassl and Vychytil.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kovarik, Kämpf, Gasser, Herdina, Breuer, Kaltenecker, Wahrmann, Haindl, Mayer, Traby, Touzeau-Roemer, Grabmeier-Pfistershammer, Kussmann, Robak, Willschke, Ay, Säemann, Schmetterer and Strassl.)

Background: During the second wave of the coronavirus disease 2019 (COVID-19) pandemic Austria suffered one of the highest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rates worldwide. We report performance parameters of a SARS-CoV‑2 screening program established for cancer outpatients at our center., Methods: Institutional policy recommended routine biweekly SARS-CoV‑2 testing. Adherence to the testing recommendation during the second wave of the COVID-19 pandemic between 1 October and 30 November 2020 was analyzed. The SARS-CoV‑2 infection rate during first wave period (21 March to 4 May 2020) was compared to the one during second wave., Results: A total of 1577 cancer patients were seen at our outpatient clinic during the second wave. In 1079/1577 (68.4%) patients, at least 1 SARS-CoV2 test was performed. Overall 2833 tests were performed, 23/1577 (1.5%, 95% confidence interval, CI 1.0-2.2%) patients were tested positive for SARS-CoV‑2, which indicates a significant increase compared to the first wave (4/1016; 0.4%, 95% CI 0.1-1.0%) with an odds ratio of 3.9 (95% CI 1.5-10.1; p < 0.005). Patients undergoing active anticancer treatment (172/960; 17.9% not tested) were more likely to have undergone a SARS-CoV‑2 test than patients in follow-up or best supportive care (326/617; 52.8% not tested p < 0.001). Furthermore, patients with only 1 visit within 4 weeks were more likely to not have undergone a SARS-CoV‑2 test (386/598; 64.5%) compared to patients with 2 or more visits (112/979; 11.4%; p < 0.001). The projected number of patients with undetected SARS-CoV‑2 infection during the study period was 5., Conclusion: We identified clinical patient parameters influencing SARS-CoV‑2 testing coverage in cancer outpatients. Our data can provide information on generation of standard operating procedures and resource allocation during subsequent infection waves., (© 2021. The Author(s).)

Background: Chronic kidney disease patients show a high mortality in cases of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV‑2) infection. Thus, information on the sero-status of nephrology personnel might be crucial for patient protection; however, limited information exists about the presence of SARS-CoV‑2 antibodies in asymptomatic individuals., Methods: We examined the seroprevalence of SARS-CoV‑2 IgG and IgM antibodies among healthcare workers of a tertiary care kidney center during the the first peak phase of the corona virus disease 2019 (COVID-19) crisis in Austria using an orthogonal test strategy and a total of 12 commercial nucleocapsid protein or spike glycoprotein-based assays as well as Western blotting and a neutralization assay., Results: At baseline 60 of 235 study participants (25.5%, 95% confidence interval, CI 20.4-31.5%) were judged to be borderline positive or positive for IgM or IgG using a high sensitivity/low specificity threshold in one test system. Follow-up analysis after about 2 weeks revealed IgG positivity in 12 (5.1%, 95% CI: 2.9-8.8%) and IgM positivity in 6 (2.6%, 95% CI: 1.1-5.6) in at least one assay. Of the healthcare workers 2.1% (95% CI: 0.8-5.0%) showed IgG nucleocapsid antibodies in at least 2 assays. By contrast, positive controls with proven COVID-19 showed antibody positivity among almost all test systems. Moreover, serum samples obtained from healthcare workers did not show SARS-CoV‑2 neutralizing capacity, in contrast to positive controls., Conclusion: Using a broad spectrum of antibody tests the present study revealed inconsistent results for SARS-CoV‑2 seroprevalence among asymptomatic individuals, while this was not the case among COVID-19 patients., Trial Registration Number: CONEC, ClinicalTrials.gov number NCT04347694., (© 2021. The Author(s).)

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., Competing Interests: NO authors have competing interests.

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: Antibody tests are essential tools to investigate humoral immunity following SARS-CoV-2 infection or vaccination. While first-generation antibody tests have primarily provided qualitative results, accurate seroprevalence studies and tracking of antibody levels over time require highly specific, sensitive and quantitative test setups., Methods: We have developed two quantitative, easy-to-implement SARS-CoV-2 antibody tests, based on the spike receptor binding domain and the nucleocapsid protein. Comprehensive evaluation of antigens from several biotechnological platforms enabled the identification of superior antigen designs for reliable serodiagnostic. Cut-off modelling based on unprecedented large and heterogeneous multicentric validation cohorts allowed us to define optimal thresholds for the tests' broad applications in different aspects of clinical use, such as seroprevalence studies and convalescent plasma donor qualification., Findings: Both developed serotests individually performed similarly-well as fully-automated CE-marked test systems. Our described sensitivity-improved orthogonal test approach assures highest specificity (99.8%); thereby enabling robust serodiagnosis in low-prevalence settings with simple test formats. The inclusion of a calibrator permits accurate quantitative monitoring of antibody concentrations in samples collected at different time points during the acute and convalescent phase of COVID-19 and disclosed antibody level thresholds that correlate well with robust neutralization of authentic SARS-CoV-2 virus., Interpretation: We demonstrate that antigen source and purity strongly impact serotest performance. Comprehensive biotechnology-assisted selection of antigens and in-depth characterisation of the assays allowed us to overcome limitations of simple ELISA-based antibody test formats based on chromometric reporters, to yield comparable assay performance as fully-automated platforms., Funding: WWTF, Project No. COV20-016; BOKU, LBI/LBG., Competing Interests: Declaration of Competing Interest Dr. Klausberger has nothing to disclose. Dr. Duerkop has nothing to disclose. Dr. Haslacher has nothing to disclose. Dr. Wozniak-Knopp has nothing to disclose. Dr. Cserjan-Puschmann has nothing to disclose. Dr. Perkmann has nothing to disclose. Dr. Lingg has nothing to disclose. Dr. Pereira Aguilar has nothing to disclose. Dr. Laurent has nothing to disclose. Dr. De Vos has nothing to disclose. Mag.rer.nat. Hofner has nothing to disclose. Dr. Holzer has nothing to disclose. Mrs. Stadler has nothing to disclose. Dipl.-Ing. Manhart has nothing to disclose. DI Vierlinger has nothing to disclose. Dr. Egger has nothing to disclose. Dipl. Ing. Milchram has nothing to disclose. Dr. Gludovacz has nothing to disclose. Dr. Marx has nothing to disclose. Dipl.-Ing. Köppl has nothing to disclose. Christopher Tauer, BSc has nothing to disclose. Jürgen Beck, MSc reports nothing to disclose. Daniel Maresch has nothing to disclose. Dr. Grünwald-Gruber has nothing to disclose. Mr. Strobl has nothing to disclose. Dr. Satzer has nothing to disclose. Dr. Stadlmayr has nothing to disclose. Ing. Vavra has nothing to disclose. Ms. Huber BSc has nothing to disclose. Dr. Wahrmann has nothing to disclose. Dr. Eskandary has nothing to disclose. Dr. Breyer has nothing to disclose. Dr. Sieghart has nothing to disclose. Dr. Quehenberger reports other from Roche Austria, personal fees from Takeda, outside the submitted work; . Dr. Leitner has nothing to disclose. Dr. Strassl has nothing to disclose. Dr. Egger has nothing to disclose. Dr. IRSARA has nothing to disclose. Dr. Griesmacher has nothing to disclose. Dr. Hoermann has nothing to disclose. Dr. Weiss has nothing to disclose. Dr. Bellmann-Weiler has nothing to disclose. Dr. Löffler-Ragg has nothing to disclose. Dr. Borth has nothing to disclose. Dr. Strasser has nothing to disclose. Dr. Jungbauer has nothing to disclose. Dr. Hahn has nothing to disclose. Dr. Mairhofer reports other from enGenes Biotech GmbH, outside the submitted work; In addition, Dr. Mairhofer has a patent PCT/EP2016/059597-Uncoupling growth and protein production issued. Dr. Hartmann has nothing to disclose. Dr. Binder reports grants from Vienna Business Agency, during the conduct of the study; and Employee of Technoclone Herstellung von Diagnostika und Arzneimitteln GmbH. Dr. Striedner reports other from enGenes GmbH, outside the submitted work; In addition, Dr. Striedner has a patent. US20180282737A1 issued to enGenes GmbH. Dr. Mach has nothing to disclose. Dr. Weinhaeusel has nothing to disclose. Dr. Dieplinger has nothing to disclose. Dr. Grebien has nothing to disclose. Dr. Gerner has nothing to disclose. Dr. Christoph Binder is board member of Technoclone GmbH. Dr. Grabherr has nothing to disclose., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Personal protective equipment and adherence to disinfection protocols are essential to prevent nosocomial severe acute respiratory syndrome coronavirus (SARS-CoV-2) transmission. Here, we evaluated infection control measures in a prospective longitudinal single-center study at the Vienna General Hospital, the biggest tertiary care center in Austria, with a structurally planned low SARS-CoV-2 exposure. SARS-CoV-2-specific antibodies were assessed by Abbott ARCHITECT chemiluminescent assay (CLIA) in 599 health care workers (HCWs) at the start of the SARS-CoV-2 epidemic in early April and two months later. Neutralization assay confirmed CLIA-positive samples. A structured questionnaire was completed at both visits assessing demographic parameters, family situation, travel history, occupational coronavirus disease 2019 (COVID-19) exposure, and personal protective equipment handling. At the first visit, 6 of 599 participants (1%) tested positive for SARS-CoV-2-specific antibodies. The seroprevalence increased to 1.5% (8/553) at the second visit and did not differ depending on the working environment. Unprotected SARS-CoV-2 exposure ( p = 0.003), positively tested family members ( p = 0.04), and travel history ( p = 0.09) were more frequently reported by positively tested HCWs. Odds for COVID-19 related symptoms were highest for congestion or runny nose ( p = 0.002) and altered taste or smell ( p < 0.001). In conclusion, prevention strategies proved feasible in reducing the risk of transmission of SARS-CoV-2 from patients and among HCWs in a low incidence hospital, not exceeding the one described in the general population.

In this case report we present a rare case of a patient with multiple risk factors for severe coronavirus disease (COVID 19) in whom intensive glucocorticoid treatment due to incipient nephrotic syndrome coincided with SARS-CoV‑2 infection. Despite this high baseline risk profile and the use of glucocorticoids the patient developed only mild disease including IgG SARS-CoV‑2 seroconversion.

Rationale: The immunologic syndrome induced by severe acute coronavirus disease 2019 (COVID-19) is yet not fully understood. Typical patterns of clinical and laboratory features match secondary hemophagocytic lymphohistiocytosis (sHLH). However, the optimal approach to COVID-19 patients testing positive for sHLH is still unclear., Patient Concerns: Three patients with COVID-19 are reviewed. All showed hyperinflammation and cytokine storm, necessitating intensive care treatment including mechanical ventilation., Diagnosis: Secondary hemophagocytic lymphohistiocytosis due to severe COVID-19; diagnosed via HScore., Interventions: A treatment regimen of methylprednisolone, pentaglobin, and anakinra was developed and administered., Outcomes: One patient survived the ICU stay. Two other patients, in whom sHLH was diagnosed too late, deceased., Lessons: A routine screening of COVID-19 patients for secondary HLH by using the HScore is feasible; especially those patients deteriorating clinically with no sufficient response to shock management might be at particular high risk. A stepwise therapeutic approach comprising corticosteroids, immunoglobulins and anakinra, accompanied by immunoadsorption, may dampen cytokine storm effects, and potentially reduce mortality., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Anti-SARS-CoV-2 vaccination of dialysis patients has been proven to be safe and effective to reduce COVID-19-related morbidity and mortality. However, data on the durability of anti-SARS-CoV-2 antibodies post-vaccination in peritoneal dialysis (PD) patients are scarce. In this prospective single-center cohort study we measured anti-SARS-CoV-2 RBD antibodies 3 and 6 months after the 3rd dose of the mRNA-1273 vaccine in 27 adult PD patients and recorded breakthrough infections. Furthermore, in a mixed model analysis, we analyzed potential factors influencing the humoral response following vaccination. Anti-SARS-CoV-2 RBD antibody levels declined from 21,424 BAU/mL at 1 month to 8397 BAU/mL at 3 months and to 5120 BAU/mL at 6 months after the 3rd dose, but remained higher than pre-3rd dose levels (212 BAU/mL). Eight patients (29.6%) were infected with SARS-CoV-2 within six months from the 3rd dose during the Omicron wave. Previous high antibody levels, high glomerular filtration rate (GFR) and low Davies Comorbidity Score were associated with higher anti-SARS-CoV-2 antibody levels after the booster. In conclusion, PD patients exhibited a robust and durable humoral response after a third dose of the mRNA-1273 vaccine. A high GFR and low comorbidity as well as previous high antibody levels predicted a better humoral response to vaccination. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic increased mortality and morbidity among immunocompromised populations. Vaccination is the most important preventive measure, however, its effectiveness among patients depending on maintenance immunoglobulin G (IgG) apheresis to control autoimmune disease activity is unknown. We aimed to examine the humoral immune response after mRNA-1273 Moderna® vaccination in immunoapheresis patients. Methods: We prospectively monitored SARS-CoV-2 IgG spike (S) protein antibody levels before and after each IgG (exposure) or lipid (LDL) apheresis (controls) over 12 weeks and once after 24 weeks. Primary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels from vaccination until week 12, secondary outcome was the difference of change of SARS-CoV2 IgG S antibody levels by apheresis treatments across groups. Results: We included 6 IgG and 18 LDL apheresis patients. After 12 weeks the median SARS-CoV-2 IgG S antibody level was 115 (IQR: 0.74, 258) in the IgG and 1216(IQR: 788, 2178) in the LDL group(p=0.03).Median SARS-CoV-2IgG S antibody reduction by apheresis was 76.4 vs. 23.7% in the IgG and LDL group (p=0.04). The average post- vs. pre-treatment SARS-CoV-2 IgG S antibody rebound in the IgG group vs.the LDL group was 46.1 and 6.44%/week from prior until week 12 visit. Conclusions: IgG apheresis patients had lower SARS-CoV-2 IgG S antibody levels compared to LDL apheresis patients, but recovered appropriately between treatment sessions. We believe that IgG apheresis itself probably has less effect on maintaining the immune response compared to concomitant immunosuppressive drugs. Immunization is recommended independent of apheresis treatment. [ABSTRACT FROM AUTHOR]