Showing papers by "Frank Hanses published in 2021"

Epidemiology of SARS-CoV-2

Abstract: SARS-CoV-2 is a recently emerged s-coronavirus. Here we present the current knowledge on its epidemiologic features. Non-systematic review. 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 (R0) 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. Despite a rapid worldwide spread, attack rates have been low in most regions, demonstrating the efficacy of control measures.

COVID-19-Associated Pulmonary Aspergillosis, March-August 2020.

Abstract: Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.

A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization.

Abstract: 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. 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. The RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R2 = 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. 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.

COVID-19 in cancer patients: clinical characteristics and outcome-an analysis of the LEOSS registry

Abstract: Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk. We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality. In total, 435 cancer patients were included in our analysis. Commonest age category was 76–85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%, p value < 0.001). After adjustments for other risk factors, mortality was comparable. Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions.

First results of the "Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS)".

Abstract: Knowledge regarding patients’ clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19. Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models. We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66–85 years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46–65 years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25–2.42, p = 0.001; 66–85 years: aOR 1.93, 95% CI 1.36–2.74, p 85 years: aOR 2.38, 95% CI 1.49–3.81, p < 0.001 vs. individuals aged 26–45 years], male sex (aOR 1.23, 95% CI 1.01–1.50, p = 0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09–1.72, p = 0.007), and diabetes (aOR 1.33, 95% CI 1.04–1.69, p = 0.023) were associated with complicated stages of COVID-19 at diagnosis. The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required.

Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone.

Abstract: 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.

Neurological symptoms and complications in predominantly hospitalized COVID-19 patients: Results of the European multinational Lean European Open Survey on SARS-Infected Patients (LEOSS).

Abstract: BACKGROUND AND PURPOSE: During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry. METHODS: We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. RESULTS: A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20-1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07-1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19. CONCLUSION: Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection.

New susceptibility loci for severe COVID-19 by detailed GWAS analysis in European populations

Abstract: Due to the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), deepening the host genetic contribution to severe COVID-19 may further improve our understanding about underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, as well as hypothesis-driven targeted analysis of the human leukocyte antigen (HLA) region and chromosome Y haplotypes. We include detailed stratified analyses based on age, sex and disease severity. In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.31 and 19q13.33 associated with severe COVID-19 with respiratory failure. These associations implicate a highly pleiotropic [~]0.9-Mb 17q21.31 inversion polymorphism, which affects lung function and immune and blood cell counts, and the NAPSA gene, involved in lung surfactant protein production, in COVID-19 pathogenesis.

Kidney injury molecule-1: potential biomarker of acute kidney injury and disease severity in patients with COVID-19.

Abstract: The aim of the current study was to evaluate whether tubular markers kidney injury molecule-1 (KIM-1) and N-acetyl-s-glucosaminidase (NAG) are related to acute kidney injury (AKI) and severe disease in patients with COVID-19. In this prospective observational clinical trial we examined a cohort of 80 patients with proof of acute respiratory infection and divided them into a COVID-19 cohort (n = 54) and a control cohort (n = 26). KIM-1 and NAG were measured from urine samples collected in the emergency department. We assessed the development of AKI, admission to the intensive care unit (ICU) and intrahospital death as clinical endpoints. Urinary KIM-1 and NAG were not significantly different between patients with SARS-CoV-2 and those with other respiratory infections (each p = n.s.). Eight patients from the COVID-19 cohort and five of the non-COVID-19-patients suffered from acute kidney injury during their stay. Nine COVID-19 patients and two non-COVID-19 patients were admitted to the ICU. KIM-1 was significantly elevated in COVID-19 patients with, compared to those without AKI (p = 0.005), as opposed to NAG and creatinine (each p = n.s.). Furthermore, KIM-1 was significantly elevated in the patients with COVID-19 that had to be transferred to the ICU (p = 0.015), in contrast to NAG and creatinine (each p = n.s.). Assessing KIM-1 in patients with COVID-19 might provide additional value in recognizing AKI at an early stage of disease. Further, KIM-1 might indicate higher risk for clinical deterioration as displayed by admission to the ICU.

Prediction of COVID-19 deterioration in high-risk patients at diagnosis: an early warning score for advanced COVID-19 developed by machine learning.

Abstract: While more advanced COVID-19 necessitates medical interventions and hospitalization, patients with mild COVID-19 do not require this. Identifying patients at risk of progressing to advanced COVID-19 might guide treatment decisions, particularly for better prioritizing patients in need for hospitalization. We developed a machine learning-based predictor for deriving a clinical score identifying patients with asymptomatic/mild COVID-19 at risk of progressing to advanced COVID-19. Clinical data from SARS-CoV-2 positive patients from the multicenter Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) were used for discovery (2020-03-16 to 2020-07-14) and validation (data from 2020-07-15 to 2021-02-16). The LEOSS dataset contains 473 baseline patient parameters measured at the first patient contact. After training the predictor model on a training dataset comprising 1233 patients, 20 of the 473 parameters were selected for the predictor model. From the predictor model, we delineated a composite predictive score (SACOV-19, Score for the prediction of an Advanced stage of COVID-19) with eleven variables. In the validation cohort (n = 2264 patients), we observed good prediction performance with an area under the curve (AUC) of 0.73 ± 0.01. Besides temperature, age, body mass index and smoking habit, variables indicating pulmonary involvement (respiration rate, oxygen saturation, dyspnea), inflammation (CRP, LDH, lymphocyte counts), and acute kidney injury at diagnosis were identified. For better interpretability, the predictor was translated into a web interface. We present a machine learning-based predictor model and a clinical score for identifying patients at risk of developing advanced COVID-19.

Specific Risk Factors for Fatal Outcome in Critically Ill COVID-19 Patients: Results from a European Multicenter Study.

Abstract: (1) Background: The aim of our study was to identify specific risk factors for fatal outcome in critically ill COVID-19 patients. (2) Methods: Our data set consisted of 840 patients enclosed in the LEOSS registry. Using lasso regression for variable selection, a multifactorial logistic regression model was fitted to the response variable survival. Specific risk factors and their odds ratios were derived. A nomogram was developed as a graphical representation of the model. (3) Results: 14 variables were identified as independent factors contributing to the risk of death for critically ill COVID-19 patients: age (OR 1.08, CI 1.06-1.10), cardiovascular disease (OR 1.64, CI 1.06-2.55), pulmonary disease (OR 1.87, CI 1.16-3.03), baseline Statin treatment (0.54, CI 0.33-0.87), oxygen saturation (unit = 1%, OR 0.94, CI 0.92-0.96), leukocytes (unit 1000/μL, OR 1.04, CI 1.01-1.07), lymphocytes (unit 100/μL, OR 0.96, CI 0.94-0.99), platelets (unit 100,000/μL, OR 0.70, CI 0.62-0.80), procalcitonin (unit ng/mL, OR 1.11, CI 1.05-1.18), kidney failure (OR 1.68, CI 1.05-2.70), congestive heart failure (OR 2.62, CI 1.11-6.21), severe liver failure (OR 4.93, CI 1.94-12.52), and a quick SOFA score of 3 (OR 1.78, CI 1.14-2.78). The nomogram graphically displays the importance of these 14 factors for mortality. (4) Conclusions: There are risk factors that are specific to the subpopulation of critically ill COVID-19 patients.

Dalbavancin as long-term suppressive therapy for patients with Gram-positive bacteremia due to an intravascular source-a series of four cases.

Abstract: 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.

Gastrointestinal bleeding and endoscopic findings in critically and non-critically ill patients with corona virus disease 2019 (COVID-19): Results from Lean European Open Survey on SARS-CoV-2 (LEOSS) and COKA registries.

Abstract: BACKGROUND: Corona virus disease 2019 (COVID-19) patients are at increased risk for thromboembolic events. It is unclear whether the risk for gastrointestinal (GI) bleeding is also increased. METHODS: We considered 4128 COVID-19 patients enrolled in the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. The association between occurrence of GI bleeding and comorbidities as well as medication were examined. In addition, 1216 patients from COKA registry were analyzed focusing on endoscopy diagnostic findings. RESULTS: A cumulative number of 97 patients (1.8%) with GI bleeding were identified in the LEOSS registry and COKA registry. Of 4128 patients from the LEOSS registry, 66 patients (1.6%) had a GI bleeding. The rate of GI bleeding in patients with intensive care unit (ICU) admission was 4.5%. The use of therapeutic dose of anticoagulants showed a significant association with the increased incidence of bleeding in the critical phase of disease. The Charlson comorbidity index and the COVID-19 severity index were significantly higher in the group of patients with GI bleeding than in the group of patients without GI bleeding (5.83 (SD = 2.93) vs. 3.66 (SD = 3.06), p < 0.01 and 3.26 (SD = 1.69) vs. 2.33 (SD = 1.53), p < 0.01, respectively). In the COKA registry 31 patients (2.5%) developed a GI bleeding. Of these, the source of bleeding was identified in upper GI tract in 21 patients (67.7%) with ulcer as the most frequent bleeding source (25.8%, n = 8) followed by gastroesophageal reflux (16.1%, n = 5). In three patients (9.7%) GI bleeding source was located in lower GI tract caused mainly by diverticular bleeding (6.5%, n = 2). In seven patients (22.6%) the bleeding localization remained unknown. CONCLUSION: Consistent with previous research, comorbidities and disease severity correlate with the incidence of GI bleeding. Also, therapeutic anticoagulation seems to be associated with a higher risk of GI bleeding. Overall, the risk of GI bleeding seems not to be increased in COVID-19 patients.

Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes.

Abstract: 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.

Solid organ transplantation is not a risk factor for COVID-19 disease outcome.

Abstract: Reports indicate an increased mortality risk for solid organ transplant recipients with COVID-19 (1, 2), which may have been influenced by clinical decision making (triage) during the early phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic In Germany, relatively few transplant recipients were infected, and the capacity of the health care system was at no point in time overwhelmed Hereby, high capacity PCR-testing including all potential organ donors, symptomatic organ recipients or other patients, as well as a relatively high number of hospitals with intensive care units (1248) as well as transplant centers (40) with high capacities allowed a completely unimpaired organ procurement and transplantation situation throughout the first wave of the pandemic despite having SARS-CoV-2 infection rates of app 2200 per million persons at the end of May 2020 Our data lead to a different assessment of the risk associated with COVID-19 after organ transplantation

Infektionen der Wirbelsäule

Abstract: Pyogene (unspezifische) Spondylodiszitis und implantatassoziierte vertebrale Osteomyelitis (IAVO) stellen wichtige Krankheitsbilder mit der Gefahr neurologischer und septischer Komplikationen dar. Die fruhzeitige Diagnostik, bei der MRT, Histopathologie und mikrobiologischer Keimnachweis zentrale Rollen spielen, ist essenziell. Ziele der konservativen Therapie bei unkomplizierter Spondylodiszitis sind die antibiotische Infektsanierung und Schmerztherapie. Im Fall von Sepsis, neurologischen Defiziten, Segmentinstabilitat oder epiduralen Abszessen sollte eine chirurgische Infektbehandlung mit Stabilisierung der Wirbelsaule erfolgen. Bei der IAVO markiert die Bildung eines reifen Biofilms den Ubergang von akuter zu chronischer Infektion. Erstere kann i.d.R. implantaterhaltend mit ausgiebigem Debridement und biofilmgangigen Antibiotika behandelt werden. Bei chronischen Infektionen ist oftmals ein Entfernen/Wechsel der Implantate notwendig, ebenfalls kombiniert mit mehrwochiger Antibiotikatherapie.

Decreased GLUT1/NHE1 RNA expression in whole blood predicts disease severity in patients with COVID-19.

Abstract: AIMS: We aimed to assess whether expression of whole-blood RNA of sodium proton exchanger 1 (NHE1) and glucose transporter 1 (GLUT1) is associated with COVID-19 infection and outcome in patients presenting to the emergency department with respiratory infections. Furthermore, we investigated NHE1 and GLUT1 expression in the myocardium of deceased COVID-19 patients. METHODS AND RESULTS: Whole-blood quantitative assessment of NHE1 and GLUT1 RNA was performed using quantitative PCR in patients with respiratory infection upon first contact in the emergency department and subsequently stratified by SARS-CoV-2 infection status. Assessment of NHE1 and GLUT1 RNA using PCR was also performed in left ventricular myocardium of deceased COVID-19 patients. NHE1 expression is up-regulated in whole blood of patients with COVID-19 compared with other respiratory infections at first medical contact in the emergency department (control: 0.0021 ± 0.0002, COVID-19: 0.0031 ± 0.0003, P = 0.01). The ratio of GLUT1 to NHE1 is significantly decreased in the blood of COVID-19 patients who are subsequently intubated and/or die (severe disease) compared with patients with moderate disease (moderate disease: 0.497 ± 0.083 vs. severe disease: 0.294 ± 0.0336, P = 0.036). This ratio is even further decreased in the myocardium of patients who deceased from COVID-19 in comparison with the myocardium of non-infected donors. CONCLUSIONS: NHE1 and GLUT1 may be critically involved in the disease progression of SARS-CoV-2 infection. We show here that SARS-CoV-2 infection critically disturbs ion channel expression in the heart. A decreased ratio of GLUT1/NHE1 could potentially serve as a biomarker for disease severity in patients with COVID-19.

[SARS-CoV-2/COVID-19-epidemiology and prevention].

Abstract: SARS-CoV‑2 („severe acute respiratory syndrome coronavirus 2“) hat sich seit Dezember 2019 rasch weltweit ausgebreitet. Eine erste Welle ist bis Ende Juni 2020 in vielen Regionen sichtbar. Wir stellen hier das aktuelle Wissen zur Epidemiologie und Pravention dar. SARS-CoV‑2 wird v. a. durch Tropfchen und Aerosole ubertragen und repliziert uberwiegend im oberen und unteren Respirationstrakt. Die Basisreproduktionszahl R0 liegt zwischen 2 und 3, die Inkubationszeit betragt im Median 6 (2–14) Tage. Wie bei den verwandten Coronaviren SARS-CoV und MERS(„Middle East respiratory syndrome“)-CoV spielen Superspreading-Ereignisse bei der Ausbreitung eine wichtige Rolle. Eine hohe Rate von Infektionen verlauft unkompliziert, moderate bis schwere Verlaufe treten bei 5–10 % der Infizierten auf. Pneumonien, kardiale Beteiligung und Thromboembolien sind die haufigsten zur Hospitalisierung fuhrenden Manifestationen. Risikofaktoren fur einen komplizierten Verlauf sind hoheres Alter, Hypertonie, Diabetes mellitus und chronische Herz- und Lungenerkrankungen sowie Immundefekte. Derzeit liegt die Schatzung fur die IFR („infection fatality rate“) uber alle Altersgruppen zwischen 0,5 und 1 %. Mit Bundeln verschiedener Masnahmen zur Reduktion sozialer Kontakte wurden Ausbruche in vielen Regionen begrenzt. Fur Deutschland wird fur die erste Welle eine Befallsrate von 0,4–1,8 % geschatzt, eine Ubersterblichkeit konnte dabei nicht beobachtet werden.

SARS-CoV-2 infectivity correlates with high viral loads and detection of viral antigen and is terminated by seroconversion.

Abstract: BACKGROUND: From a public health perspective, effective containment strategies for 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 PCR, viral antigen by point-of-care assay, time since onset of symptoms and presence of SARS-CoV-2 IgG antibodies in the context of virus isolation from respiratory specimen. 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 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 above 10 7 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with 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.

Influenza vaccination coverage among emergency department personnel is associated with perception of vaccination and side effects, vaccination availability on site and the COVID-19 pandemic.

Abstract: Introduction Influenza is a major concern in hospitals, including the emergency department (ED), mainly because of a high risk for ED personnel to acquire and transmit the disease. Although influenza vaccination is recommended for health care workers, vaccination coverage is low. Methods This survey was conducted in the 2016/2017 and 2020/2021 influenza seasons. Questionnaires were sent to ED personnel in 12 hospitals in Bavaria, South-Eastern Germany. The response rates were 62% and 38% in 2016/2017 and 2020/2021, respectively. Data were compared between the two seasons as well as between vaccinated and not vaccinated respondents in 2020/2021. Results Significantly more ED personnel reported having been vaccinated in the 2020/2021 season. Factors associated with vaccination coverage (or the intention to get vaccinated) were profession (physician / medical student), having been vaccinated at least twice, the availability of an influenza vaccination on site (in the ED) as well as the COVID-19 pandemic. Additionally, significant differences in the assessment and evaluation of influenza, its vaccination side effects and ethical aspects were found between vaccinated and not vaccinated ED personnel in 2020/2021. Unvaccinated respondents estimated higher frequencies of almost all potential vaccination side effects, were less likely to accept lay-offs if employees would not come to work during an influenza pandemic and more likely to agree that work attendance should be an employee´s decision. Vaccinated participants instead, rather agreed that vaccination should be mandatory and were less likely to consider job changes in case of a mandatory vaccination policy. Conclusion The COVID-19 pandemic might have contributed to a higher influenza vaccination rate among ED workers. Vaccination on site and interventions targeting the perception of influenza vaccination and its side effects may be most promising to increase the vaccination coverage among ED personnel.

All-cause mortality and disease progression in SARS-CoV-2-infected patients with or without antibiotic therapy: an analysis of the LEOSS cohort.

Abstract: Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary. 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) ≤ 0.5 ng/ml. The analysis took the confounders gender, age, and comorbidities into account. Three thousand, six hundred twenty-seven cases matched all inclusion criteria for analyses. For the primary endpoint, antibiotic treatment was not correlated with lower all-cause mortality or progression to the next more advanced (critical) phase (n = 996) (both p > 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05). In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients.

Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.

Abstract: Aims Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity. Methods and results We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators. Conclusion These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.

Machine Learning Based Prediction of COVID-19 Mortality Suggests Repositioning of Anticancer Drug for Treating Severe Cases

Abstract: Despite available vaccinations COVID-19 case numbers around the world are still growing, and effective medications against severe cases are lacking. In this work, we developed a machine learning model which predicts mortality for COVID-19 patients using data from the multi-center Lean European Open Survey on SARS-CoV-2-infected patients (LEOSS) observational study (>100 active sites in Europe, primarily in Germany), resulting into an AUC of almost 80%. We showed that molecular mechanisms related to dementia, one of the relevant predictors in our model, intersect with those associated to COVID-19. Most notably, among these molecules was tyrosine kinase 2 (TYK2), a protein that has been patented as drug target in Alzheimers Disease but also genetically associated with severe COVID-19 outcomes. We experimentally verified that anti-cancer drugs Sorafenib and Regorafenib showed a clear anti-cytopathic effect in Caco2 and VERO-E6 cells and can thus be regarded as potential treatments against COVID-19. Altogether, our work demonstrates that interpretation of machine learning based risk models can point towards drug targets and new treatment options, which are strongly needed for COVID-19.