Bridging basic science and applied diagnostics: Comprehensive viral diagnostics enabled by graphene-based electronic biosensor technology advancements.

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.

A Microbiology Analytics Tool to Evaluate the Burden of Antibiotic-Resistant Infections.

Leveraging the capabilities of a microbiological clinical analytics tool, this study delves into quantifying the public health impact of antibiotic-resistant bacteria. Focusing on eight predominant antibiotic-resistant bacteria, the study utilizes University Hospital Vienna's data to calculate the burden of antibiotic-resistant infections in disability-adjusted life years. The results highlight the potential of extended analytics tools in epidemiological research and underscore the pressing challenge of antimicrobial drug resistance.

Left ventricular assist device-associated driveline infections as a specific form of complicated skin and soft tissue infection/acute bacterial skin and skin structure infection - issues and therapeutic options.

PURPOSE OF REVIEW: This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines. RECENT FINDINGS: Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as 'off-label' for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients' outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition. SUMMARY: We argue that driveline infections meet the criteria for ABSSSI which would enlarge the 'on-label' antibiotic armamentarium for treating these severe infections, thereby improving the patients' quality of life.

Expert Opinion on Dose Regimen and Therapeutic Drug Monitoring for Long-Term Use of Dalbavancin: Expert Review Panel.

BACKGROUND: Dalbavancin is a lipoglycopeptide with a long elimination half-life and is currently licensed for the treatment of acute bacterial skin and skin structure infections in adults. Dalbavancin's potential in treating off-label complex Gram-positive infections is promising and real-world experience in treating such infections is growing. However, clear guidance on extended dosing regimens is lacking. OBJECTIVES: This study aimed to provide clear expert opinion based on recent pharmacokinetic literature and expert and real-world experience in infection areas that require > 2 weeks of treatment. METHODS: A single face-to-face meeting was held in September 2022 to collate expert opinion and present safety data of dalbavancin use in these clinical indications. A survey was completed by all authors on their individual experience with dalbavancin, which highlighted the heterogeneity in the regimens that were used. RESULTS: After review of the survey data and recent literature, this study presents expert panel proposals that accommodate different healthcare settings and resource availability, and centre around the length of treatment duration including up to or exceeding 6 weeks. To achieve adequate dalbavancin concentrations for up to 6 weeks, 3000 mg of dalbavancin should be given over 4 weeks for the agreed complex infections requiring > 2 weeks of treatment. Therapeutic drug monitoring (TDM) is advised for longer treatment durations and in cases of renal failure. Specific dosing recommendations for other special populations require further investigation. CONCLUSIONS: These proposals based on expert opinion have been defined to encourage best practice with dalbavancin, to optimise its administration beyond the current approved licenced dose across different healthcare settings.

Microbiological and Virological Knowledge-Based Alert Service.

Hospital wards need immediate information about multi-resistant pathogens and contagious viruses in their hospitalized patients. An alert service configurable with Arden-Syntax-based alert definitions passing through an ontology service to complement results from microbiology and virology with high-level terms was implemented as proof of concept. Integration into the University Hospital Vienna's IT landscape is ongoing.

Long COVID symptoms in hospital employees after post-vaccination SARS-CoV-2 infection in Austria: A study on self-reported incidence and associated factors.

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.

Modeling the protective effect of previous compulsory smallpox vaccination against human monkeypox infection: from hypothesis to a worst-case scenario.

OBJECTIVES: Human monkeypox (MPX) cases are escalating worldwide. Smallpox vaccination, which was compulsory in Austria until 1981, was reported to confer 85% cross-protection against MPX. METHODS: To assess the impact of smallpox vaccine-induced protection, the age-dependent vaccine-induced immunity against human MPX and the probability of infection according to age in the general population of Vienna, Austria, were determined using a modified susceptible-infected-removed model. RESULTS: Within the population born before 1981, the average vaccine-induced protective effect was calculated at 50.4%, whereas in the population born thereafter, protection was lacking. The overall probability of infection after exposure to an infected patient was calculated at 73.8%, which exceeds the threshold value of 46.9% for an index patient to infect at least one other person (R ≥1.0). CONCLUSION: Our model shows that if no additional interventions are taken, the collective immunization status of the population alone will not suffice to contain human MPX. Although the majority of cases have occurred in a subpopulation, given the steadily increasing incidence, dissemination into the general population remains possible, as observed before with HIV. Our model emphasizes the need for adequate containment measures and may aid in specific risk assessment because it can easily be adapted to other populations and cohorts worldwide.

Reusable respirators as personal protective equipment in clinical practice : User experience in times of a pandemic.

BACKGROUND: The novel strain of severe acute respiratory syndrome coronavirus 2 is highly contagious; therefore, special emphasis must be given to personal protective equipment for healthcare workers. Reusable elastomeric respirators were previously used in intensive care units (ICU). These respirators include full or half masks and devices modified to accommodate a filter. Although the general comfort of masks used in the ICU has been studied, data comparing multiple types of masks during a pandemic are missing. METHODS: A prospective randomized trial was conducted in an ICU. After standardized training, participants were randomized to use one of three mask types (full, half or snorkelling mask), each fitted with a filter equivalent to a class 3 particle-filtering half mask (FFP3) during one shift. The main outcomes were characteristics of using the mask itself (donning/doffing, quality of seal, cleaning), working conditions with the mask (vision, comfort, perceived safety, communication) and a subjective comparison to single-use FFP2/3 masks. RESULTS: A total of 30 participants were included in the trial, randomized to 10 participants per group. The masks were worn 6.4 (4.5) times (mean SD) for a total duration of 132 (66) min per shift. The tested masks were rated 7 (2.6) (mean SD) in comparison to FFP2/3 on a Likert scale (0: worst, 10: best). Significant differences between the masks were found in respect to comfort (7/4/8), donning (8/7/9), overall rating (8/5/8) and comparison to single-use FFP2/3 masks (9/7/9; full-, half, snorkelling mask). CONCLUSION: Using reusable elastomeric masks is feasible in clinical practice. Full face masks were significantly better in terms of comfort, donning, overall rating and in comparison to single-use FFP2/3 masks.

Ischemic Priapism in a 12 Year Old Patient Associated With Coronavirus Disease 2019 (COVID-19): A Case Report.

Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been associated with changes in blood coagulation resulting in increased incidence of venous thromboembolic events and coagulopathy. Moreover, single cases of ischemic priapism have been reported in adult patients with SARS-CoV-2 infection. In this report, we describe the case of ischemic priapism in a 12-year-old child with recent SARS- CoV-2 infection.

Postvaccination infections among staff of a tertiary care hospital after vaccination with severe acute respiratory syndrome coronavirus 2 vector and mRNA-based vaccines.

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.

A Longitudinal Seroprevalence Study Evaluating Infection Control and Prevention Strategies at a Large Tertiary Care Center with Low COVID-19 Incidence.

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.

Diagnosis of COVID-19 using multiple antibody assays in two cases with negative PCR results from nasopharyngeal swabs.

We report of two cases of progressed COVID-19 with negative PCR tests from nasopharyngeal swabs, in whom diagnosis was made by different antibody assays, including a lateral flow rapid test and multiple commercial ELISAs, finally confirmed by comprehensive serological assays. These cases highlight that commercial ELISAs and even rapid tests might significantly aid the diagnosis of COVID-19, particularly, if a combination of serological assays is used with a specific clinical question, in severely ill patients after seroconversion and when comprehensive serological methods are used for confirmation.

Letermovir for the compassionate therapeutic use of cytomegalovirus infection.

PURPOSE: Data on the efficacy, dosing and safety of letermovir for the compassionate therapeutic use of CMV infections are limited. METHODS: Clinical and virological efficacy of letermovir was assessed in a retrospective single-centre study of patients who received letermovir for the compassionate therapeutic use of CMV infections. RESULTS: Letermovir initiation yielded prompt treatment response in 7 out of 9 patients (77.7%). CONCLUSION: Letermovir may be an effective and well tolerated option in the compassionate treatment of CMV infections, although recurrence of CMV and emergence of resistance may be issues.

COVID-19: IgG seroconversion under intensive glucocorticoid treatment in a high-risk patient with minimal change disease.

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-CoV­2 infection. Despite this high baseline risk profile and the use of glucocorticoids the patient developed only mild disease including IgG SARS-CoV­2 seroconversion.

Diagnostic accuracy of two commercially available rapid assays for detection of IgG and IgM antibodies to SARS-CoV-2 compared to ELISA in a low-prevalence population.

Background: New commercially available point-of-care (POC) immunodiagnostic tests are appearing, which may yield rapid results for anti-SARS-CoV-2 antibodies. The aim of this study was to evaluate the diagnostic accuracy of rapid antibody detection tests compared to a validated laboratory-based enzyme-linked immunosorbent assay (ELISA) and to investigate infections amongst healthcare workers (HCWs) after unprotected close contact to COVID-19 patients. Methods: Blood serum and whole blood of 130 participants were tested with NADAL® COVID-19 IgG/IgM rapid test and mö-screen 2019-NCOV coronavirus test against a validated ELISA test. Infection status was evaluated using real-time polymerase-chain-reaction. Results: Acute COVID-19 infection was detected in 2.4% of exposed HCWs. Antibody tests showed an overall frequency of IgG and IgM in 5.3%, with 1.6% asymptomatic infections. The NADAL® test showed a sensitivity (IgM/IgG) of 100% (100%/100%), a specificity (IgM/IgG) of 98.8% (97.6%/100 %), a PPV of 76.9% (57.1%/100%), an NPV of 100% (100%/100%), and a diagnostic accuracy of 98.8% (97.7%/100%). The mö-screen test had a sensitivity (IgM/IgG) of 90.9% (80%/100%), a specificity (IgM/IgG) of 98.8% (97.6%/100%), a PPV of 76.9% (57.1%/100%), an NPV of 99.6% (99.2%/100%), and a diagnostic accuracy of 98.5% (96.9%/100%). Conclusions: The frequency of COVID-19 infections in HCWs after unprotected close contact is higher than in the general population of a low-prevalence country. Both POC tests were useful for detecting IgG, but did not perform well for IgM, mainly due to false positive results.

Unexpected complete recovery of a patient with severe tick-borne encephalitis treated with favipiravir.

We report a case of tick-borne encephalitis (TBE) in a 22-year-old man, who was admitted to the Medical University of Vienna hospital with severe meningoencephalitis, unresponsive and dependent on a respirator. He had given a history of a recent tick bite, but because he had previously received a full course of vaccination against TBE, West Nile virus infection was suspected. Because the antiviral drug favipiravir has been reported to be active against WNV, therapy was initiated, and continued even after a diagnosis of TBE was confirmed, due to significant improvement of symptoms. Within days, the patient's symptoms resolved, and he was discharged after complete recovery at 15 days after onset. Although this single case does not permit any conclusion as to the role of favipiravir in the favorable outcome, it suggests that the drug should be further evaluated in laboratory animal models and in appropriate clinical settings.

Calculated parenteral initial treatment of bacterial infections: Infections with multi-resistant Gram-negative rods - ESBL producers, carbapenemase-producing Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii.

This is the sixteenth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. Infections due to multiresistant Gram-negative rods are challenging. In this chapter recommendations for targeted therapy for infections caused by ESBL-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii are given, based on the limited available evidence.