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Background: We assessed the diagnostic value of FDG PET/CT in a real-world cohort of patients with surgically managed infective endocarditis (IE)., Methods: We performed a retrospective analysis of all patients hospitalized in a tertiary IE referral medical center from January 2014 to October 2018 fulfilling the following criteria: ICD-10 code for IE and OPS code for both, heart surgery and FDG PET/CT., Results: Final analysis included 29 patients, whereof 28 patients had surgically proven IE. FDG PET/CT scan was true-positive in 15 patients (sensitivity (SEN) 56%) and false-negative in 12 patients. Combination of Duke criteria (DC) with FDG PET/CT scan resulted in gain of SEN for all patients with confirmed IE (SEN of DC 79% vs SEN of combination DC and FDG PET/CT 89%), driven by a relevant gain in PVE patients only (SEN of DC 78% vs SEN of combination DC and FDG PET/CT 94%). Interestingly, higher prosthesis age was observed in patients with false-negative scans., Conclusions: We found a SEN of 56% for FDG PET/CT in a real-world cohort of patients with surgically proven IE which was associated with a 16% gain of IE diagnosis in patients with PVE when combined with DC., (© 2020. The Author(s).)

Background: In a previous study, we had investigated the intensive care course of patients with coronavirus disease 2019 (COVID-19) in the first wave in Germany by calculating models for prognosticating in-hospital death with univariable and multivariable regression analysis. This study analyzed if these models were also applicable to patients with COVID-19 in the second wave., Methods: This retrospective cohort study included 98 critical care patients with COVID-19, who had been treated at the University Medical Center Regensburg, Germany, between October 2020 and February 2021. Data collected for each patient included vital signs, dosage of catecholamines, analgosedation, anticoagulation, and antithrombotic medication, diagnostic blood tests, treatment with extracorporeal membrane oxygenation (ECMO), intensive care scores, ventilator therapy, and pulmonary gas exchange. Using these data, expected mortality was calculated by means of the originally developed mathematical models, thereby testing the models for their applicability to patients in the second wave., Results: Mortality in the second-wave cohort did not significantly differ from that in the first-wave cohort (41.8% vs. 32.2%, p = 0.151). As in our previous study, individual parameters such as pH of blood or mean arterial pressure (MAP) differed significantly between survivors and non-survivors. In contrast to our previous study, however, survivors and non-survivors in this study showed significant or even highly significant differences in pulmonary gas exchange and ventilator therapy (e.g. mean and minimum values for oxygen saturation and partial pressure of oxygen, mean values for the fraction of inspired oxygen, positive expiratory pressure, tidal volume, and oxygenation ratio). ECMO therapy was more frequently administered than in the first-wave cohort. Calculations of expected mortality by means of the originally developed univariable and multivariable models showed that the use of simple cut-off values for pH, MAP, troponin, or combinations of these parameters resulted in correctly estimated outcome in approximately 75% of patients without ECMO therapy., Competing Interests: The authors have declared that no competing interests exist.

SARS-CoV-2 Omicron is the first pandemic variant of concern exhibiting an abrupt accumulation of mutations particularly in the receptor-binding domain that is a critical target of vaccination induced and therapeutic antibodies. Omicron's mutations did only marginally affect the binding of ACE2, and the two antibodies Sotrovimab and CR3022 but strongly impaired the binding of Casirivimab and Imdevimab. Moreover, as compared with Wuhan, there is reduced serum reactivity and a pronounced loss of competitive surrogate virus neutralization (sVN) against Omicron in naïve vaccinees and in COVID-19 convalescents after infection and subsequent vaccination. Finally, although the booster vaccination response conferred higher titers and better sVN, the effect was nonetheless significantly lower compared with responses against Wuhan. Overall, our data suggest that the antigenicity of Omicrons receptor binding motive has largely changed but antibodies such as Sotrovimab targeting other conserved sites maintain binding and therefore hold potential in prophylaxis and treatment of Omicron-induced COVID-19., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Background: Reactogenicity of coronavirus disease 2019 (COVID-19) vaccines can result in inability to work. The object of this study was to evaluate health care workers' sick leave after COVID-19 vaccination and to compare it with sick leave due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and quarantine leave., Methods: A multicenter cross-sectional survey was conducted at Regensburg University Medical Center and 10 teaching hospitals in South-East Germany from July 28 to October 15, 2021., Results: Of 2662 participants, 2309 (91.8%) were fully vaccinated without a history of SARS-CoV-2 infection. Sick leave after first/second vaccination occurred in 239 (10.4%) and 539 (23.3%) participants. In multivariable logistic regression, the adjusted odds ratio for sick leave after first/second vaccination compared with BNT162b2 was 2.26/3.72 for mRNA-1237 (95% CI, 1.28-4.01/1.99-6.96) and 27.82/0.48 for ChAdOx1-S (95% CI, 19.12-40.48/0.24-0.96). The actual median sick leave (interquartile range [IQR]) was 1 (0-2) day after any vaccination. Two hundred fifty-one participants (9.4%) reported a history of SARS-CoV-2 infection (median sick leave [IQR] 14 [10-21] days), 353 (13.3%) were quarantined at least once (median quarantine leave [IQR], 14 [10-14] days). Sick leave due to SARS-CoV-2 infection (4642 days) and quarantine leave (4710 days) accounted for 7.7 times more loss of workforce than actual sick leave after first and second vaccination (1216 days) in all fully vaccinated participants., Conclusions: Sick leave after COVID-19 vaccination is frequent and is associated with the vaccine applied. COVID-19 vaccination should reduce the much higher proportion of loss of workforce due to SARS-CoV-2 infection and quarantine., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The long-term course of immunity among individuals with a history of COVID-19, in particular among those who received a booster vaccination, has not been well defined so far., Methods: SARS-CoV-2-specific antibody levels were measured by ELISA over 1 year among 136 health care workers infected during the first COVID-19 wave and in a subgroup after booster vaccination approximately 1 year later. Furthermore, spike-protein-reactive memory T cells were quantified approximately 7 months after the infection and after booster vaccination. Thirty healthy individuals without history of COVID-19 who were routinely vaccinated served as controls., Results: Levels of SARS-CoV-2-specific IgM- and IgA-antibodies showed a rapid decay over time, whereas IgG-antibody levels decreased more slowly. Among individuals with history of COVID-19, booster vaccination induced very high IgG- and to a lesser degree IgA-antibodies. Antibody levels were significantly higher after booster vaccination than after recovery from COVID-19. After vaccination with a two-dose schedule, healthy control subjects developed similar antibody levels as compared to individuals with history of COVID-19 and booster vaccination. SARS-CoV-2-specific memory T cell counts did not correlate with antibody levels. None of the study participants suffered from a reinfection., Conclusions: Booster vaccination induces high antibody levels in individuals with a history of COVID-19 that exceeds by far levels observed after recovery. SARS-CoV-2-specific antibody levels of similar magnitude were achieved in healthy, COVID-19-naïve individuals after routine two-dose vaccination., (© 2021. The Author(s).)

Objectives: In Germany, deaths of SARS-CoV-2-positive persons are reported as 'death related to SARS-CoV-2/COVID-19' to the Robert Koch Institute, Germany's main infectious disease institution. In 177 COVID-19-associated deaths reported in Regensburg, Germany, from October 2020 to January 2021, we investigated how deaths following SARS-CoV-2 infection were reported and whether cases with a death attributed to SARS-CoV-2 (COVID-19 death [CD]) differed from cases with a reported death from other causes (non-COVID-19 death [NCD])., Study Design: This was an observational retrospective cohort study., Methods: We analysed descriptive data on the numbers of cases, deaths, age, sex, symptoms and hospitalizations. We calculated odds ratios (ORs) with 95% confidence intervals (95% CIs) and performed Chi-squared/Fisher's exact test for categorical variables and the Wilcoxon rank-sum test for comparison of medians., Results: Deaths attributed to COVID-19 occurred primarily in elderly patients. The mortality rate and the case fatality ratio (CFR) increased with age. The median age and the prevalence of risk factors were similar between CD and NCD. Respiratory symptoms and pneumonia at the time of diagnosis were associated with death reported as CD. The odds of CD attribution in cases hospitalized because of COVID-19 were 6-fold higher than the odds of NCD (OR: 6.00; 95% CI: 1.32 to 27.22)., Conclusions: Respiratory symptoms/pneumonia at the time of diagnosis and hospitalization due to COVID-19 were associated with attributing a death to COVID-19. Numbers of COVID deaths need to be interpreted with caution. Criteria that facilitate attributing the cause of death among SARS-CoV-2 cases more uniformly could make these figures more comparable., (Copyright © 2022 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Heterologous SARS-CoV-2 vaccine approaches with a second mRNA-based vaccine have been favored in the recommendations of many countries over homologous vector-based ChAdOx1 nCoV-19 vaccination after reports of thromboembolic events and lower efficacy of this regimen. In the middle of 2021, the SARS-CoV-2 Delta variant of concern (VoC) has become predominant in many countries worldwide. Data addressing the neutralization capacity of a heterologous ChAdOx1 nCoV-19/mRNA-based vaccination approach against the Delta VoC in comparison to the widely used homologous mRNA-based vaccine regimen are limited. Here, we compare serological immune responses of a cohort of ChAdOx1 nCoV-19/BNT162b2-vaccinated participants with those of BNT162b2/BNT162b2 vaccinated ones and show that neutralization capacity against the Delta VoC is significantly increased in sera of ChAdOx1 nCoV-19/BNT162b2-vaccinated participants. This overall effect can be attributed to ChAdOx1 nCoV-19/BNT162b2-vaccinated women, especially those with more severe adverse effects leading to sick leave following second immunization., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Introduction: The aim of this study was to investigate the adherence to vaccinations, especially pneumococcal vaccinations, in lung cancer patients., Methods: the study was performed at the University Hospital Regensburg, Germany. All patients with a regular appointment scheduled between 1 December 2020 and 29 April 2021 and who provided informed consent were included. Available medical records, vaccination certificates, and a questionnaire were analyzed., Results: we included 136 lung cancer patients (NSCLC n = 113, 83.1%, SCLC n = 23, 16.9%). A correct pneumococcal vaccination according to national recommendations was performed in 9.4% (12/127) of the patients. A correct vaccination was performed for tetanus in 50.4% (66/131), diphtheria in 34.4% (44/128), poliomyelitis in 25.8% (33/128), tick-borne encephalitis in 40.7% (24/59), hepatitis A in 45.5% (7/11), hepatitis B in 38.5% (5/13), shingles in 3.0% (3/101), measles in 50.0% (3/6), pertussis in 47.7% (62/130), influenza in 54.4% (74/136), and meningococcal meningitis in 0% (0/2) of the patients., Conclusion: adherence to pneumococcal vaccinations, as well as to other vaccinations, is low in lung cancer patients.

Background: From a public health perspective, effective containment strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be balanced with individual liberties., Methods: We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time polymerase chain reaction, viral antigen by point-of-care assay, time since onset of symptoms, and the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies in the context of virus isolation from respiratory specimens., Results: The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with the presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads >107 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with negative predictive values of 93.8% and 96.0%., Conclusions: Our data support quarantining patients with high viral load and detection of viral antigen and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Coronavirus disease 2019 (Covid-19) vaccination is essential to fight the pandemic. Health care workers (HCWs) are prioritized to get vaccinated, yet uptake of recommended vaccinations is known to be low in this group. In a tertiary care university hospital with a high number of Covid-19 patients in intensive care, 59.5% of surveyed staff (N = 2454) were willing to get vaccinated, 21.4% were unsure and 18.7% refused. Vaccine hesitancy was higher in female, younger and healthy employees without contact to Covid-19 patients; nurses (53.3%) were much less willing to get vaccinated compared to physicians (82.7%)., (© 2021. The Author(s).)

Background: Vaccinations are among the most effective preventative healthcare measures. The aim of this cross-sectional study was to evaluate the adherence of adults with pre-existing pulmonary conditions to the national vaccination schedule and to identify reasons for poor adherence., Methods: All patients with an appointment at Donaustauf hospital between October 2019 and April 2020 were asked to bring their vaccination certificates for evaluation and to compete a questionnaire. To determine the adherence vaccination certificates and patients' comorbidities were correlated with the national recommendations of the German Standing Committee on Vaccination (STIKO)., Results: 571 (65.6%) of all patients believed that their vaccination status was up-to-date. An appropriate vaccination status according to national recommendations (STIKO) was documented as follows: tetanus 56.4% (375/665), diphtheria 43.2% (292/676), poliomyelitis 28.5% (189/662), tick-borne encephalitis 45.4% (300/659), hepatitis A 31.0% (18/58), hepatitis B 34.6% (27/78), shingles 1.2% (6/489), influenza 21.0% (125/596, season 2019/2020), measles 38.3% (31/81), rubella 33.3% (7/21), pneumococcal disease 29.5% (175/593), pertussis 54.2% (365/674) and haemophilus influenza type b 100% (1/1). Adherence to rabies (0/2), varicella (0/28), meningococcal type ACWY (0/36) and type b (0/36) was 0%. 72% of patients would follow a physician's recommendation to get vaccinated., Conclusion: Adherence to STIKO recommendations was poor. However, patients are willing to follow a physician's recommendation for vaccination., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation., (© 2020. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non-COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment.

Background: Data of critically ill COVID-19 patients are being evaluated worldwide, not only to understand the various aspects of the disease and to refine treatment strategies but also to improve clinical decision-making. For clinical decision-making in particular, prognostic factors of a lethal course of the disease would be highly relevant., Methods: In this retrospective cohort study, we analyzed the first 59 adult critically ill Covid-19 patients treated in one of the intensive care units of the University Medical Center Regensburg, Germany. Using uni- and multivariable regression models, we extracted a set of parameters that allowed for prognosing in-hospital mortality., Results: Within the cohort, 19 patients died (mortality 32.2%). Blood pH value, mean arterial pressure, base excess, troponin, and procalcitonin were identified as highly significant prognostic factors of in-hospital mortality. However, no significant differences were found for other parameters expected to be relevant prognostic factors, like low arterial partial pressure of oxygen or high lactate levels. In the multivariable logistic regression analysis, the pH value and the mean arterial pressure turned out to be the most influential prognostic factors for a lethal course., Competing Interests: The authors have declared that no competing interests exist.

It is not clear whether there is an association between adverse reactions and immune response after vaccination. Seven hundred and thirty-five vaccinees from our University Medical Center vaccination clinic provided information about sex, age and adverse reactions after first and second vaccination with BNT162b2. Adverse reactions were categorized into three groups: no or minor on the injection side, moderate (not further classified) and severe-defined as any symptom(s) resulting in sick leave. We chose 38 vaccinees with the most severe adverse reactions and compared their humoral and T-cell-mediated immune responses after second vaccination with those of 38 sex and age matched controls without or only minor injection-side related adverse reactions. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-receptor binding domain (RBD) IgG titers were detectable in all participants (median 5528; range 958-26,285). Men with severe adverse reactions had 1.5-fold higher median SARS-CoV-2 RBD IgG titers compared to men without adverse reactions (median 7406 versus 4793; p < 0.001). Similarly; neutralization activity was significantly higher in men with severe adverse reactions (half maximal inhibitory concentrations (IC 50 ) median 769 versus 485; p < 0.001). Reactogenicity did not influence humoral immune response in women nor T-cell-mediated immune response in any sex. To conclude; adverse reactions after vaccination with BNT162b2 do influence humoral immune response yet only in men and are not a prerequisite for a robust antibody response.

Background: The role of venovenous extracorporeal membrane oxygenation (VV ECMO) in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) still remains unclear. Our aim was to investigate the clinical course and outcome of those patients and to identify factors associated with the need for prolonged ECMO therapy., Methods: A retrospective single-center study on patients with VV ECMO for COVID-19-associated ARDS was performed. Baseline characteristics, ventilatory and ECMO parameters, and laboratory and virological results were evaluated over time. Six months follow-up was assessed., Results: Eleven of 16 patients (68.8%) survived to 6 months follow-up with four patients requiring short-term (<28 days) and seven requiring prolonged (⩾28 days) ECMO support. Lung compliance before ECMO was higher in the prolonged than in the short-term group (28.1 (28.8-32.1) ml/cmH 2 O vs 18.7 (17.7-25.0) ml/cmH 2 O, p = 0.030). Mechanical ventilation before ECMO was longer (19 (16-23) days vs 5 (5-9) days, p = 0.002) and SOFA score was higher (12.0 (10.5-17.0) vs 10.0 (9.0-10.0), p = 0.002) in non-survivors compared to survivors. Low viral load during the first days on ECMO tended to indicate worse outcomes. Seroconversion against SARS-CoV-2 occurred in all patients, but did not affect outcome., Conclusions: VV ECMO support for COVID-19-induced ARDS is justified if initiated early and at an experienced ECMO center. Prolonged ECMO therapy might be required in those patients. Although no relevant predictive factors for the duration of ECMO support were found, the decision to stop therapy should not be made dependent of the length of ECMO treatment.

Abstract: Antibiotic stewardship (ABS) programs intend to improve outcomes of nosocomial infections and to counteract the emergence of further antimicrobial resistances. At the anesthesiologic-neurosurgical intensive care unit (ICU) of the University Medical Center Regensburg (Germany) we implemented a standard operating procedure (SOP) with clear instructions for the preanalytical handling and storage of microbiological samples. We intended to find out whether the instructions given in the SOP led to a higher rate of ideal material being sent to the laboratory and to overall better quality of the received results.We retraced retrospectively all samples taken in cases of suspected pneumonia, urinary tract infection, bloodstream infection, catheter infection associated with a central venous or arterial catheter and ventriculitis due to external ventricular drainage as well as all smears taken for the screening for multi-resistant bacteria within a time period of 1 year before to 1 year after the implementation of the SOP.In the case of suspected pneumonia and urinary tract infection, large amounts of ideal material were sent to the microbiological laboratory. A remarkable improvement after the implementation of the SOP, however, could only be observed regarding the number of urine samples taken from older urinary catheters, which was significantly lower in the "SOP group". Samples for microbiological diagnostics were taken much more often in the daytime, although storage of the probes did not lead to worse results.Concrete instructions enable adequate preanalytical handling of microbiological probes. However, we could not recognize substantial improvements probably due to a preexisting high process quality on the ICU. Microbiological diagnostics during the night shift has to be improved., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To follow serological immune responses of front-line healthcare workers after PCR-confirmed COVID-19 for a mean of 30 weeks, describe the time-course of SARS-CoV-2 spike protein-specific IgG, IgA and IgM levels and to identify associations of the immune response with symptoms, demographic parameters and severity of disease., Methods: Anti-SARS-CoV-2 S protein-specific IgG, IgA and IgM antibodies were measured at three time points during the 30-week follow-up. COVID-19-specific symptoms were assessed with standardized questionnaires., Results: 95% of the participants mounted an IgG response with only modest decline after week 12. IgG-type antibodies were still detectable in almost 90% of the subjects at 30 weeks. IgA and IgM responses were less robust and antibody titers decreased more rapidly. At 30 weeks, only 25% still had detectable IgA-type and none had IgM-type antibodies. Higher age and higher disease severity were independently associated with higher IgG antibody levels, albeit with wide variations., Conclusion: Serological immune responses after COVID-19 show considerable inter-individual variability, but show an association with increasing age and higher severity of disease. IgG-type anti-SARS-CoV-2 antibodies remain positive in 90% of the individuals 30 weeks after onset of symptoms., (© 2021. The Author(s).)

Background: COVID-19 is a syndrome caused by the recently emerged SARS-CoV-2. We collected clinical and epidemiologic data in an almost complete cohort of SARS-CoV-2 positive individuals from Regensburg, Germany, from March 2020 to May 2020., Methods: Analysis of a retrospectively documented cohort of consecutive COVID-19 cases recorded between March 7, 2020 and May 24, 2020 as part of an infection control investigation program, with prospective follow-up interviews gathering information on type and duration of symptoms and COVID-19 risk factors until June 26, 2020., Results: Of 1089 total cases, 1084 (99.5%) cases were included. The incidence during the time period was 315.4/100,000, lower than in the superordinate government district Oberpfalz (468.5/100,000) and the overall state of Bavaria (359.7/100,000). The case fatality ratio (CFR) was 2.1%. Among fatal cases, the mean age was 74.4 years and 87% presented with known risk factors, most commonly chronic heart disease, chronic lung disease, kidney disease, and diabetes mellitus. 897 cases (82.7%) showed at least one symptom, most frequently cough (45%) and fever (41%). Further, 18% of cases suffered from odour/taste disorder. 17% of total cases reported no symptoms. The median duration of general illness was 10 days. During follow-up, 8.9% of 419 interviewed cases reported at least one symptom lasting at least 6 weeks, and fatigue was the most frequent persistent symptom., Discussion: We report data on type and duration of symptoms, and clinical severity of nearly all (99.5%) patients with SARS-CoV-2 recorded from March 2020 to May 2020 in Regensburg. A broad range of symptoms and symptom duration was seen, some of them lasting several weeks in a considerable number of cases. The case-fatality ratio was 2.1%. Asymptomatic cases may be underrepresented due to the nature of the study., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment., (© 2021. The Author(s).)

Background: The vaccinations against the "severe acute respiratory syndrome coronavirus type 2" (SARS-CoV‑2) play a decisive role in the global fight against the coronavirus pandemic. In the population, but also among health care workers (HCWs), there were concerns and skepticism about vaccinations even before the corona pandemic., Methods: An online survey on the attitude of HCWs to vaccination against SARS-CoV‑2 was carried out in December (December 3rd-December 12th, 2020) before and in February (February 1st-February 10th, 2021) after the start of the vaccinations. Members of the German Society for Internal Intensive Care Medicine and Emergency Medicine (DGIIN) and the German Interdisciplinary Association for Intensive Care Medicine and Emergency Medicine (DIVI) were invited by email and on Facebook., Results: In December 2305 and in February 3501 people took part. The approval rate for vaccination increased from 85.2% to 92.1% (p < 0.001). There was also an increase in willingness to vaccinate (63.8% vs. 75.9%; p < 0.001). The female gender, membership of the professional group nursing staff and age < 45 years were significantly associated with a restricted willingness to vaccinate. There was also a decrease in concerns about efficacy, side effects and long-term damage. There was clear skepticism about the vaccine from AstraZeneca (Cambridge, United Kingdom). Before and after the introduction of vaccinations against SARS-CoV‑2, an increase in the willingness to vaccinate against SARS-CoV-2 can be shown in German HCWs. Technical experts must bring objectivity into the currently controversial debate through precise and transparent information and thus counteract vaccination skepticism, not only among HCWs.

Coronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA is detected by reverse-transcription quantitative real-time PCR (RT-qPCR) from respiratory specimens. This study compares throat washings (TW), nasopharyngeal swabs (NS) and oropharyngeal swabs (OS). A total of 102 samples from 34 adult patients with confirmed SARS-CoV-2 infection were analysed by RT-qPCR with absolute quantification. The median concentrations and diagnostic sensitivities were 5.8×104 copies/mL, 85% (NS), 1.4×104, 79% (OS) and 4.3×103, 85% (TW). Concentration differences were significant between NS and TW ( P = 0.019). Saliva (SA) was available from 21 patients (median 3.4×103). OS and TW can be considered for SARS-CoV-2 diagnostics, although with slightly lower concentrations.

Background: The antibacterial effect of antibiotics is linked to the free drug concentration. This study investigated the applicability of an ultrafiltration method to determine free plasma concentrations of beta-lactam antibiotics in ICU patients., Methods: Eligible patients included adult ICU patients treated with ceftazidime (CAZ), meropenem (MEM), piperacillin (PIP)/tazobactam (TAZ), or flucloxacillin (FXN) by continuous infusion. Up to 2 arterial blood samples were drawn at steady state. Patients could be included more than once if they received another antibiotic. Free drug concentrations were determined by high-performance liquid chromatography with ultraviolet detection after ultrafiltration, using a method that maintained physiological conditions (pH 7.4/37°C). Total drug concentrations were determined to calculate the unbound fraction. In a post-hoc analysis, free concentrations were compared with the target value of 4× the epidemiological cut-off value (ECOFF) for Pseudomonas aeruginosa as a worst-case scenario for empirical therapy with CAZ, MEM or PIP/tazobactam and against methicillin-sensitive Staphylococcus aureus for targeted therapy with FXN., Results: Fifty different antibiotic treatment periods in 38 patients were evaluated. The concentrations of the antibiotics showed a wide range because of the fixed dosing regimen in a mixed population with variable kidney function. The mean unbound fractions (fu) of CAZ, MEM, and PIP were 102.5%, 98.4%, and 95.7%, with interpatient variability of <6%. The mean fu of FXN was 11.6%, with interpatient variability of 39%. It was observed that 2 of 12 free concentrations of CAZ, 1 of 40 concentrations of MEM, and 11 of 23 concentrations of PIP were below the applied target concentration of 4 × ECOFF for P. aeruginosa. All concentrations of FXN (9 samples from 6 patients) were >8 × ECOFF for methicillin-sensitive Staphylococcus aureus., Conclusions: For therapeutic drug monitoring purposes, measuring total or free concentrations of CAZ, MEM, or PIP is seemingly adequate. For highly protein-bound beta-lactams such as FXN, free concentrations should be favored in ICU patients with prevalent hypoalbuminemia., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: SARS-CoV-2 is a recently emerged ß-coronavirus. Here we present the current knowledge on its epidemiologic features., Methods: Non-systematic review., Results: SARS-CoV-2 replicates in the upper and lower respiratory tract. It is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The consensus estimate for the basis reproduction number (R 0 ) is between 2 and 3, and the median incubation period is 5.7 (range 2-14) days. Similar to SARS and MERS, superspreading events have been reported, the dispersion parameter (kappa) is estimated at 0.1. Most infections are uncomplicated, and 5-10% of patients are hospitalized, mainly due to pneumonia with severe inflammation. Complications are respiratory and multiorgan failure; risk factors for complicated disease are higher age, hypertension, diabetes, chronic cardiovascular, chronic pulmonary disease and immunodeficiency. Nosocomial and infections in medical personnel have been reported. Drastic reductions of social contacts have been implemented in many countries with outbreaks of SARS-CoV-2, leading to rapid reductions. Most interventions have used bundles, but which of the measures have been more or less effective is still unknown. The current estimate for the infection's fatality rate is 0.5-1%. Using current models of age-dependent infection fatality rates, upper and lower limits for the attack rate in Germany can be estimated between 0.4 and 1.6%, lower than in most European countries., Conclusions: Despite a rapid worldwide spread, attack rates have been low in most regions, demonstrating the efficacy of control measures.

A 21-year-old woman was hospitalized due to coronavirus disease 2019 (COVID-19)-associated respiratory and hepatic impairment concomitant with severe hemolytic anemia. Upon diagnosis of secondary hemophagocytic lymphohistiocytosis, immunosuppression with anakinra and steroids was started, leading to a hepatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viremia. Subsequent liver biopsy revealed virus particles in hepatocytes by electron microscopy and SARS-CoV-2 virus could be isolated and cultured. Immunosuppression was stopped and convalescent donor plasma given. In the differential diagnosis, an acute crisis of Wilson's disease was raised by laboratory and genetic testing. This case highlights the complexity of balancing immunosuppression to control hyperinflammation versus systemic SARS-CoV-2 dissemination., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We present four cases with Gram-positive bacteremia (pathogens: MRSA n = 1, Enterococcus spp. n = 3) due to an intravascular source (left ventricular assist device: n = 2, transfemoral aortic valve implantation n = 1, prosthetic aortic valve: n = 1) where no curative treatment was available. These patients received indefinite, chronic suppressive (palliative) therapy with dalbavancin (500 mg weekly or 1000 mg biweekly regimens). Outcomes and clinical characteristics are described; treatment was effective in suppression of bacteremia in all patients over several months (range: 1 to more than 12 months), we observed no relevant side effects.

Objective: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels., Methods: In our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated., Results: The RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R 2  = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%; N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection; N = 53) in serum., Conclusions: With the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.

Cause and mechanisms of persistent dyspnoea after recovery from COVID-19 are not well described. The objective is to describe causal factors for persistent dyspnoea in patients after COVID-19. We examined patients reporting dyspnoea after recovery from COVID-19 by cardiopulmonary exercise testing. After exclusion of patients with pre-existing lung diseases, ten patients (mean age 50±13.1 years) were retrospectively analysed between May 14 th and September 15 th , 2020. On chest computed tomography, five patients showed residual ground glass opacities, and one patient showed streaky residua. A slight reduction of the mean diffusion capacity of the lung for carbon monoxide was noted in the cohort. Mean peak oxygen uptake was reduced with 1512±232 ml/min (72.7% predicted), while mean peak work rate was preserved with 131±29 W (92.4% predicted). Mean alveolar-arterial oxygen gradient (AaDO 2 ) at peak exercise was 25.6±11.8 mmHg. Mean value of lactate post exercise was 5.6±1.8 mmol/l. A gap between peak work rate in (92.4% predicted) to peak oxygen uptake (72.3% pred.) was detected in our study cohort. Mean value of lactate post exercise was high in our study population and even higher (n.s.) compared to the subgroup of patients with reduced peak oxygen uptake and other obvious reason for limitation. Both observations support the hypothesis of anaerobic metabolism. The main reason for dyspnoea may therefore be muscular., (©Copyright: the Author(s).)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread globally since December 2019. A first wave is visible up to the end of June 2020 in many regions. This article presents a review of the current knowledge on the epidemiology and prevention. The SARS-CoV‑2 predominantly replicates in the upper and lower respiratory tracts and is particularly transmitted by droplets and aerosols. The estimate for the basic reproduction number (R 0 ) is between 2 and 3 and the median incubation period is 6 days (range 2-14 days). As with the related SARS-CoV and Middle East respiratory syndrome (MERS-CoV), superspreading events play an important role in the dissemination. A high proportion of infections are uncomplicated but moderate or severe courses develop in 5-10% of infected persons. Pneumonia, cardiac involvement and thromboembolisms are the most frequent manifestations leading to hospitalization. Risk factors for a complicated course are high age, hypertension, diabetes mellitus and chronic cardiovascular and pulmonary diseases as well as immunodeficiency. Currently, the estimation for the infection fatality rate (IFR) is between 0.5% and 1% across all age groups. Outbreaks were limited in many regions with bundles of various measures for reduction of social contacts. The incidence for the first wave in Germany can be estimated as 0.4-1.8% and excess mortality could not be observed., (© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2020.)

A retrospective, single-center analysis of 14 cases of Candida endocarditis (from 355 candidemia cases during the years 2012-2019) revealed a high in-hospital mortality (57.1%), a high proportion of healthcare-associated infections (13/14) and a high treatment preference for echinocandins. Transthoracic echocardiography and 18 F-FDG PET/CT had a sensitivity of 54.5% and 57.1%, respectively. Patients were older than previously described and most patients with Candida endocarditis had persistent candidemia for ≥ 3 days despite antifungal therapy.

Background: We analyzed the epidemiology of COVID-19 in Regensburg after the first wave ended in June 2020 and compared it with patients' characteristics and symptoms in late summer/early autumn 2020. Methods: Retrospective analysis of epidemiological data from Regensburg (city/county) on age and initial symptoms as reported during case investigation for containment. Observed periods: March 7, 2020 to June 6, 2020 and August 12, 2020 to October 9, 2020. Results: The proportion of asymptomatic persons who tested positive for SARS-COV-2 in the second period was 55% (286 of 520 cases), whereas during the first wave from March to June 2020 this percentage was 14.4% (169 of 1,170 cases). A comparison of typical symptoms shows that the most common symptoms of COVID-19 in the first wave (cough, fever and generally feeling ill) were less often reported in the second period: cough 14% vs. 42%, fever 17% vs. 38%, general signs of illness 14% vs. 22% in the second vs. first period, respectively overall cases were younger in the second period, the median age of asymptomatic cases was comparable in both periods. The case fatality rate for the first period was 2.1%, in the second it was 0.2%. Discussion: The epidemiological situation in the second period is different from that during the first wave. We observed a considerable proportion of questionable cases in August/September 2020 (asymptomatic cases, high ct values, often only detection of one gene). False positive cases/non-contagious cases have to be taken into account for this period. On-demand or free-of-charge testing for asymptomatic persons will lower the positive predictive value of tests and place a high burden on finite capacities., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Lampl et al.)

Introduction: The aim of this study was to analyse use of and adherence to influenza and pneumococcal vaccination in high-risk patients with chronic pulmonary disease., Methods: The study was initiated at the Centre of Pneumology in Donaustauf, Germany. All patients with asthma bronchiale (AB), chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) that were treated in a pneumological Non-ICU ward, in the sleep laboratory or in the outpatient's clinic between October 1st , 2019 and March 26th , 2020 and provided informed consent were included. Vaccination certificates and a vaccination-centred questionnaire were analysed in relation to vaccination status, risk factors, patient characteristics., Results: 133 patients with COPD, 68 patients with AB and 104 patients with ILD were included. PCV13/PPSV23 vaccination only (no sequential vaccination) was performed in less than 10%/33% of all patients. Sequential vaccination of PCV13 and PPSV23 was performed in 12.8% of COPD, 7.4% of AB patients and 13.5% of ILD patients. Influenza vaccination was performed in less than 30% of all patients. Vaccinations were mainly performed by general practitioners (GPs) and rarely by specialists of pulmonary care (<6%). 67% of all patients were seen by a specialist in pulmonary care in the last 36 months, but in less than 15% the vaccination status was evaluated., Discussion: Use of and adherence for PPSV23 and influenza vaccinations is low in patients with COPD, AB and ILD in south east Germany., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new β‑Coronavirus that was first detected in 2019 in Wuhan, China. In the ensuing months it has been transmitted worldwide. Here the authors present the current knowledge on the epidemiology of this virus. SARS-CoV‑2 replicates mainly in the upper and lower respiratory tract and is primarily transmitted by droplets from asymptomatic and symptomatic infected subjects. The estimate for the basic reproduction number (R) is currently between 2 and 3, while the incubation period is 6 (median, range 2-14) days. Although most infections are uncomplicated, 5-10% of cases develop pneumonia, which can lead to hospitalization, respiratory failure and multiorgan failure. Risk factors for a complicated disease course include age, hypertension, chronic cardiovascular and pulmonary disease and immunodeficiency. The overall case fatality rate is 1.4%, with the rate rising in the sixth decade of life. Nosocomial and infections in medical personnel have been reported. Drastic reductions in social contact have been implemented in many countries with outbreaks of SARS-CoV‑2, leading to rapid reductions in R. Which of the measures have been effective is still unknown.

The transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan and Hubei Province differ considerably from those in the rest of China. In Hubei province SARS-CoV‑2 led to a dramatic outbreak. Intensive control measures (travel restrictions, isolation of cases, quarantine of contacts and others) led to the control of the outbreak. Despite travel restrictions SARS-CoV‑2 was detected in other provinces in the following weeks. Consistent and intensive identification and isolation of infected persons ("containment") was able to prevent an outbreak outside Hubei province, providing an example for the control of SARS-CoV‑2.

With increasing number of SARS-CoV-2 infections and COVID-19 patients to be taken care of by the health system, more and more health workers become affected by the disease. It has been reported that right from the beginning of the outbreak in Lombardy up to 20% of the doctors and nurses became infected. Under these circumstances, the regular operation of health institutions already suffering from a shortage of staff becomes difficult. This has led to complete or partial shutdowns of hospitals, either due to a lack of uninfected personnel or because of uncontrollable chains of infection endangering patients. In one of the largest university perinatal center in Bavaria with more than 3000 births per year, an outbreak of COVID-19 occurred in March 2020, affecting 36 staff members, including doctors, nurses, and midwives. Here, we describe the outbreak and present the measures contributing to the successful containment of the outbreak within three weeks. At the same time, clinical services could be maintained, however, not without deployment of personnel exposed to employees infected with SARS-CoV-2. Apart from massive testing of personnel in pre-defined phases and increased hygiene measures, including a general obligation to wear surgical face masks, we identified the need to monitor cases of illness across all groups of employees, to ensure social distancing within personnel and to evaluate contacts of clinical personnel outside of the hospital environment, in order to be able to interpret chains of infections and to disrupt them. Overall, only a bundle of measures is needed to contain such an outbreak., (© 2020 The Authors. Pediatric Allergy and Immunology published by John Wiley & Sons Ltd.)

The clinical course of coronavirus disease 2019 (COVID-19) varies from mild symptoms to acute respiratory distress syndrome, hyperinflammation, and coagulation disorder. The hematopoietic system plays a critical role in the observed hyperinflammation, particularly in severely ill patients. We conducted a prospective diagnostic study performing a blood differential analyzing morphologic changes in peripheral blood of COVID-19 patients. COVID-19 associated morphologic changes were defined in a training cohort and subsequently validated in a second cohort (n = 45). Morphologic aberrations were further analyzed by electron microscopy (EM) and flow cytometry of lymphocytes was performed. We included 45 COVID-19 patients in our study (median age 58 years; 82% on intensive care unit). The blood differential showed a specific pattern of pronounced multi-lineage aberrations in lymphocytes (80%) and monocytes (91%) of patients. Overall, 84%, 98%, and 98% exhibited aberrations in granulopoiesis, erythropoiesis, and thrombopoiesis, respectively. Electron microscopy revealed the ultrastructural equivalents of the observed changes and confirmed the multi-lineage aberrations already seen by light microscopy. The morphologic pattern caused by COVID-19 is characteristic and underlines the serious perturbation of the hematopoietic system. We defined a hematologic COVID-19 pattern to facilitate further independent diagnostic analysis and to investigate the impact on the hematologic system during the clinical course of COVID-19 patients., Competing Interests: The authors declare no competing interests and no financial support for this study., (© 2020 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P<0.001). In both groups, vaccine regimens induced HIV-specific polyfunctional CD4 and CD8 T cells and the production of Th1, Th2 and Th17/IL-21 cytokines. Antibody responses were also elicited in up to 81% of vaccines. A higher percentage of IgG responders was noted in the 2xDNA arm compared to the 3xDNA arm, while the 3xDNA group tended to elicit a higher magnitude of IgG3 response against specific Env antigens. We show here that the modulation of the prime strategy, without modifying the route or the dose of administration, or the combination of vectors, may influence the quality of the responses., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: The authors declare that they have no conflict of interest.

Antibiotic stewardship (ABS) is an important measure to counteract the spread of resistant pathogens and multidrug resistance. The most important ABS tools include the implementation of local guidelines, the development of a house-related list of anti-infective agents, regular ABS visits and practice-oriented internal training events. Effective strategies for therapy optimization include indication testing and therapy evaluation, dose optimization as well as determining an appropriate duration of therapy. Oralization of anti-infectives (sequence therapy) should be supported by consistent clinical criteria in in-house guidelines. The incidence of Clostridioides difficile infections (CDI) can be more than halved by restricting the so-called "4C antibiotics". Point-of-care tests help to minimize the use of antibiotics in the outpatient setting. Vaccination reduces the need for antibiotic therapy.

Against the background of increasing antimicrobial resistance, antibiotic stewardship (ABS) is an important measure to counteract the spread of resistant pathogens and multidrug resistance. For Germany and Austria, a comprehensive S3 guideline is available, which was last updated in 2018. The control of antibiotic or anti-infective use in hospitals should be guided by specialized ABS teams. At the hospital level, ABS also includes a structured ongoing analysis of local antibiotic use and resistance data. Recommendations for locally adapted therapy regimens should be derived and implemented from this data analysis. ABS consists of regular ward rounds ("ABS visits"), during which members of the ABS team review the indication, dosage, route of administration and duration of antimicrobial therapy at the bedside. Here, the key challenge is to save antibiotics without compromising the individual patient. Digitalization and artificial intelligence offer new options for ABS, while the adaption of inpatient concepts to outpatient care is also important.

Background: The aim of this study was to analyse temporal changes in the epidemiology of candidemia assessing patient's characteristics, risk factors, diagnostic management, treatment, and outcome in a tertiary care hospital in South Eastern Germany., Methods: In this retrospective cohort study patients with blood cultures positive for Candida spp. were identified from the microbiological database in the years 2006-2018. A detailed collection of patients' characteristics was obtained for the time periods 2006-2008 and 2016-2018. Risk factors for survival were analysed in a logistic regression analysis., Results: In the years 2006-2018, a total of 465 episodes of candidemia were identified. An increase in candidemia cases was evident in the period of 2016-2018 compared to 2006-2015 and to 2006-2008 in absolute numbers and adjusted to patient-days. C. albicans was responsible for 62.8% of cases in 2006-2008 and 51.2% of all cases in the years 2016-2018, respectively, whereas there was a significant increase of C. glabrata in the latter period (16.3-31.5%). Overall mortality was not significantly different in the two periods. Infectious diseases consultation led to a lower mortality of patients with candidemia and to a higher adherence to guidelines. In multivariate analysis, only complete change or extraction of intravascular indwelling material and female gender were independent predictors for survival., Conclusion: We observed an increase in candidemia rates and rates of non-albicans spp. over time. A complete change of all catheters and/or indwelling devices improved survival. ID consultation led to a better guideline adherence.

Background: In 2018-19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report the occurrence of BoDV-1-associated encephalitis in cases submitted to the Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany, and provide a detailed description of newly identified cases of BoDV-1-induced encephalitis., Methods: All brain tissues from 56 encephalitis cases from Bavaria, Germany, of putative viral origin (1999-2019), which had been submitted for virological testing upon request of the attending clinician and stored for stepwise diagnostic procedure, were systematically screened for BoDV-1 RNA. Two additional BoDV-1-positive cases were contributed by other diagnostic centres. Positive results were confirmed by deep sequencing, antigen detection, and determination of BoDV-1-reactive antibodies in serum and cerebrospinal fluid. Clinical and epidemiological data from infected patients were collected and analysed., Findings: BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analysed encephalitis cases and the first human BoDV-1 isolate was obtained from an unequivocally confirmed human BoDV-1 infection from the endemic area. Six of the eight BoDV-1-positive patients had no record of immunosuppression before the onset of fatal disease, whereas two were immunocompromised after solid organ transplantation. Typical initial symptoms were headache, fever, and confusion, followed by various neurological signs, deep coma, and severe brainstem involvement. Seven of nine patients with fatal encephalitis of unclear cause were BoDV-1 positive within one diagnostic centre. BoDV-1 sequence information and epidemiological analyses indicated independent spillover transmissions most likely from the local wild animal reservoir., Interpretation: BoDV-1 infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spillover infections in horses and sheep. BoDV-1 infection can result in fatal encephalitis in immunocompromised and apparently healthy people. Consequently, all severe encephalitis cases of unclear cause should be tested for bornaviruses especially in endemic regions., Funding: German Federal Ministry of Education and Research., (Copyright © 2020 Elsevier Ltd. All rights reserved.)