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1.
Viruses ; 14(7)2022 06 28.
Article in English | MEDLINE | ID: covidwho-1911660

ABSTRACT

Pathogen-associated molecular patterns, including cytoplasmic DNA and double-strand (ds)RNA trigger the induction of interferon (IFN) and antiviral states protecting cells and organisms from pathogens. Here we discovered that the transfection of human airway cell lines or non-transformed fibroblasts with 24mer dsRNA mimicking the cellular micro-RNA (miR)29b-1* gives strong anti-viral effects against human adenovirus type 5 (AdV-C5), influenza A virus X31 (H3N2), and SARS-CoV-2. These anti-viral effects required blunt-end complementary RNA strands and were not elicited by corresponding single-strand RNAs. dsRNA miR-29b-1* but not randomized miR-29b-1* mimics induced IFN-stimulated gene expression, and downregulated cell adhesion and cell cycle genes, as indicated by transcriptomics and IFN-I responsive Mx1-promoter activity assays. The inhibition of AdV-C5 infection with miR-29b-1* mimic depended on the IFN-alpha receptor 2 (IFNAR2) and the RNA-helicase retinoic acid-inducible gene I (RIG-I) but not cytoplasmic RNA sensors MDA5 and ZNFX1 or MyD88/TRIF adaptors. The antiviral effects of miR29b-1* were independent of a central AUAU-motif inducing dsRNA bending, as mimics with disrupted AUAU-motif were anti-viral in normal but not RIG-I knock-out (KO) or IFNAR2-KO cells. The screening of a library of scrambled short dsRNA sequences identified also anti-viral mimics functioning independently of RIG-I and IFNAR2, thus exemplifying the diverse anti-viral mechanisms of short blunt-end dsRNAs.


Subject(s)
COVID-19 , Interferon Type I , MicroRNAs , Antiviral Agents/pharmacology , DEAD Box Protein 58/genetics , DEAD Box Protein 58/metabolism , DEAD-box RNA Helicases/genetics , Humans , Influenza A Virus, H3N2 Subtype/genetics , Interferon Type I/genetics , RNA, Double-Stranded , SARS-CoV-2
2.
Int J Environ Res Public Health ; 19(13)2022 Jun 22.
Article in English | MEDLINE | ID: covidwho-1911327

ABSTRACT

Throughout the COVID-19 pandemic, mental health of individuals with bipolar disorders (BD) is potentially more vulnerable, especially regarding COVID-19-related regulations and associated symptomatic changes. A multicentric online study was conducted in Austria, Germany, and Denmark during the COVID-19 pandemic. Overall, data from 494 participants were collected (203 individuals with BD, 291 healthy controls (HC)). Participants filled out questionnaires surveying emotional distress due to social distancing, fear of COVID-19, and the Brief Symptom Inventory-18 to assess symptom severity at four points of measurement between 2020 and 2021. General linear mixed models were calculated to determine the difference between the groups in these pandemic specific factors. Individuals with BD reported higher distress due to social distancing than HC, independently of measurement times. Fear of COVID-19 did not differ between groups; however, it was elevated in times of higher infection and mortality due to COVID-19. Individuals with BD reported higher psychiatric symptom severity than HC; however, symptom severity decreased throughout the measured time in the pandemic. Overall, individuals with BD experienced more distress due to the COVID-19 situation than HC. A supportive mental health system is thus recommended to ensure enhanced care, especially in times of strict COVID-19-related regulations.


Subject(s)
Bipolar Disorder , COVID-19 , Psychological Distress , Austria/epidemiology , Bipolar Disorder/epidemiology , COVID-19/epidemiology , Denmark/epidemiology , Germany/epidemiology , Humans , Pandemics , Physical Distancing
3.
Nat Med ; 28(6): 1141-1148, 2022 06.
Article in English | MEDLINE | ID: covidwho-1900513

ABSTRACT

Research and practice in critical care medicine have long been defined by syndromes, which, despite being clinically recognizable entities, are, in fact, loose amalgams of heterogeneous states that may respond differently to therapy. Mounting translational evidence-supported by research on respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-suggests that the current syndrome-based framework of critical illness should be reconsidered. Here we discuss recent findings from basic science and clinical research in critical care and explore how these might inform a new conceptual model of critical illness. De-emphasizing syndromes, we focus on the underlying biological changes that underpin critical illness states and that may be amenable to treatment. We hypothesize that such an approach will accelerate critical care research, leading to a richer understanding of the pathobiology of critical illness and of the key determinants of patient outcomes. This, in turn, will support the design of more effective clinical trials and inform a more precise and more effective practice at the bedside.


Subject(s)
COVID-19 , SARS-CoV-2 , Critical Care , Critical Illness , Humans , Syndrome
4.
Zeitschrift für Politikwissenschaft ; : 1-18, 2022.
Article in German | EuropePMC | ID: covidwho-1897605

ABSTRACT

Krisen testen die Leistungsfähigkeit von Verwaltungen unter Realbedingungen. Vor diesem Hintergrund analysiert der vorliegende Beitrag Reaktion der deutschen Kommunalverwaltung auf die Fluchtmigration zwischen 2015 und 2017 und auf die erste Welle der COVID-19-Pandemie in 2020. Mit Blick auf die Debatte zum organisationalen Lernen in Ausnahmesituationen liegt der Schwerpunkt der Analyse auf der Rolle administrativer Netzwerke sowie der Lernfähigkeit von öffentlichen Behörden während sowie zwischen Krisensituationen. Die Auswertung zweier Umfragen unter Mitarbeitern der deutschen Kommunalverwaltung zeigt erstens, dass die Qualität der verwaltungsinternen und der zivilgesellschaftlichen Vernetzung von zentraler Bedeutung für administrative Krisenperformanz sind. Zweitens korrespondiert Leistungsfähigkeit in Krisen mit der Bereitschaft sowie mit der Fähigkeit, Lehren aus früheren Krisen zu ziehen.

5.
Zeitschrift für Politikwissenschaft ; 2022.
Article in German | PMC | ID: covidwho-1894707

ABSTRACT

Krisen testen die Leistungsfähigkeit von Verwaltungen unter Realbedingungen. Vor diesem Hintergrund analysiert der vorliegende Beitrag Reaktion der deutschen Kommunalverwaltung auf die Fluchtmigration zwischen 2015 und 2017 und auf die erste Welle der COVID-19-Pandemie in 2020. Mit Blick auf die Debatte zum organisationalen Lernen in Ausnahmesituationen liegt der Schwerpunkt der Analyse auf der Rolle administrativer Netzwerke sowie der Lernfähigkeit von öffentlichen Behörden während sowie zwischen Krisensituationen. Die Auswertung zweier Umfragen unter Mitarbeitern der deutschen Kommunalverwaltung zeigt erstens, dass die Qualität der verwaltungsinternen und der zivilgesellschaftlichen Vernetzung von zentraler Bedeutung für administrative Krisenperformanz sind. Zweitens korrespondiert Leistungsfähigkeit in Krisen mit der Bereitschaft sowie mit der Fähigkeit, Lehren aus früheren Krisen zu ziehen.

6.
JMIR Res Protoc ; 11(5): e33023, 2022 May 19.
Article in English | MEDLINE | ID: covidwho-1875275

ABSTRACT

BACKGROUND: Informal carers play a significant role in supporting people living with dementia; however, carers in rural areas are often isolated, with limited access to support services. Although dementia-friendly communities provide valued support for carers, access to them is limited as they are few and geographically dispersed. OBJECTIVE: This study's aim was to increase support and services for rural informal carers of people living with dementia by using information and communication technologies accessed through an integrated website and mobile app-the Verily Connect app. The objective of this protocol is to detail the research design used in a complex study that was situated in a challenging real-world setting integrating web-based and on-ground technology and communication. Therefore, it is anticipated that this protocol will strengthen the research of others exploring similar complex concepts. METHODS: A stepped-wedge, open-cohort cluster randomized controlled trial was conducted to implement Verily Connect across 12 rural Australian communities. The Verily Connect intervention delivered web-based, curated information about dementia, a localized directory of dementia services and support, group and individual chat forums, and peer support through videoconference. During the implementation phase of 32 weeks, Verily Connect was progressively implemented in four 8-weekly waves of 3 communities per wave. Usual care, used as a comparator, was available to carers throughout the study period. Participants and researchers were unblinded to the intervention. There were 3 cohorts of participants: carers, volunteers, and staff; participants were recruited from their communities. The primary outcome measure was perceived carer social support measured using the Medical Outcomes Study-Social Support Survey. Volunteers and staff provided feedback on their participation in Verily Connect as qualitative data. Qualitative data were collected from all cohorts of participants through interviews and focus groups. Process evaluation data were collected through interviews and memos written by research staff. Data on the costs of implementing Verily Connect were collected by the research team members and evaluated by a health economist. RESULTS: Between August 2018 and September 2019, a total of 113 participants were recruited. There were 37 (32.7%) carers, 39 (34.5%) volunteers, and 37 (32.7%) health service staff. The study was complex because of the involvement of multiple and varied communities of carers, volunteers, health service staff, and research team members originating from 5 universities. Web-based technologies were used as intervention strategies to support carers and facilitate the process of undertaking the study. CONCLUSIONS: The Verily Connect trial enabled the testing and further development of a web-based approach to increasing support for carers of people living with dementia across a diverse rural landscape in Australia. This protocol provides an example of how to conduct a pragmatic evaluation of a complex and co-designed intervention involving multiple stakeholders. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618001213235; https://tinyurl.com/4rjvrasf. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/33023.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317584

ABSTRACT

Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV 229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counterselection and challenge with the β-coronaviruses OC43 and SARS-CoV-2 in tissue culture and human airway epithelial explant cultures (HAEEC) identified four FDA-approved compounds with oral availability. Methylene blue (MB, used for the treatment of methemoglobinemia), Mycophenolic acid (MPA, used in organ transplantion) and the anti-fungal agent Posaconazole (POS) had the broadest anti-CoV spectrum. They inhibited the shedding of SARS CoV 2 and variants-of-concern (alpha, beta, gamma) from HAEEC in either pre- or post exposure regimens at clinically relevant dosage. Co-treatment of cultured cells with MB and the FDA-approved SARS-CoV-2 RNA-polymerase inhibitor Remdesivir reduced the effective anti-viral dosage of MB by 2-fold, and Remdesivir by 4 to 10-fold, indicated by BLISS independence syner-gy modelling. Neither MB, MPA or POS affected the cell delivery of SARS-CoV-2 or OC43 (+)sense RNA, but blocked subsequent viral RNA accumulation in cells. Unlike Remdesivir, MB, MPA or POS did not reduce the release of viral RNA in post exposure regimen, thus indicating infection inhibition at a post-replicating step as well. In summary, the data emphasize the power of unbiased, full cycle compound screens to identify and repurpose broadly acting drugs against coronaviruses.Funding Information: We acknowledge financial support from the Swiss National Science foundation (SNSF) to UFG and GT (31CA30_196177 / 1), the NCCR Chemical Biology supported by the SNSF for purchasing the BSF-EPFL repurposing collection, and a special Coronavirus Research grant from the University of Zurich to UFG. Declaration of Interests: UFG has been a consultant and stock owner in 3V-Biosciences (now Sagimet Biosciences), and a consultant to F. Hoffmann-La Roche Ltd. The authors filed a patent application on the use of MPA for the treatment of COVID-19 (EP20213904, European Patent Office, University of Zurich).Ethical Approval: Nasal polyp epithelial cells and bronchial epithelial cells were purchased from Epithelix SARL (Geneva, Switzerland). Mucilair™ cells were reconstituted from patients undergoing surgical nasal polypectomy or bronchial biopsies, respectively. All samples from Epithelix SARL were obtained with informed consent, according to the declaration of Helsinki on biomedical research (Hong Kong amendment, 1989), and received approval from local ethics committee (commission cantonale d’éthique de la recherche CCER de Genève).Coronavirus storage and procedures have been registered and validated by the Swiss Federal Office for the Environment (Bundesamt für Umwelt, BAFU) and the Swiss Federal Office of Public Health (Bundesamt für Gesundheit, BAG);Ecogen A203032-00, registered the 01-Sep-2020 for a duration of 5-years for the University of Zurich (Department of Molecular Life Sciences).

8.
Psychiatry Res ; 310: 114451, 2022 04.
Article in English | MEDLINE | ID: covidwho-1683546

ABSTRACT

The COVID-19 pandemic affects both mentally healthy and ill individuals. Individuals with bipolar disorder (BD) constitute an especially vulnerable group. A multicentric online study was conducted in Austria, Denmark, and Germany after the first lockdown phase in 2020. In total, 117 healthy controls (HC) were matched according to age and sex to 117 individuals with BD. The survey included the Brief Symptom Inventory-18, Beck Depression Inventory-2, Pittsburgh Sleep Quality Index, and a self-constructed questionnaire assessing COVID-19 fears, emotional distress due to social distancing, lifestyle, and compliance to governmental measures. In individuals with BD, increased symptoms of depression, somatization, anxiety, distress due to social distancing, and poorer sleep quality were related to emotional distress due to social distancing. The correlation between emotional distress due to social distancing and anxiety showed 26% of shared variance in BD and 11% in HC. Negative lifestyle changes and lower compliance with COVID-19 regulatory measures were more likely to be observed in individuals with BD than in HC. These findings underscore the need for ongoing mental health support during the pandemic. Individuals with BD should be continuously supported during periods of social distancing to maintain a stable lifestyle and employ strategies to cope with COVID-19 fears.


Subject(s)
Bipolar Disorder , COVID-19 , Bipolar Disorder/complications , Bipolar Disorder/epidemiology , Communicable Disease Control , Humans , Pandemics , SARS-CoV-2
9.
Pharmacopsychiatry ; 55(1): 5-6, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1655722

ABSTRACT

The COVID-19 pandemic is causing a major burden on personal health, healthcare systems and the global economy. For the last two years the COVID-19 pandemic has dramatically changed our lives in many personal and professional areas. For millions of us, due to infection rates, but also to protection measures such as lockdowns the corona pandemic has significantly changed the way we work, how we live, and how we interact with technology. In addition to the development of effective vaccines, anti-viral and anti-inflammation strategies are of eminent importance to treat people with acute infection or at least prevent serious negative outcomes. In contrast to the fast development of several effective vaccines that were remarkably available already after one year of the pandemic, novel effective anti-viral compounds are still in development. The only currently used effective medications against severe SARS-CoV-2 virus infection are corticosteroids 1.


Subject(s)
COVID-19 , Psychopharmacology , Communicable Disease Control , Humans , Pandemics , SARS-CoV-2
10.
Curr Res Virol Sci ; 3: 100019, 2022.
Article in English | MEDLINE | ID: covidwho-1635770

ABSTRACT

Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV-229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counter selection and challenge with the ß-coronaviruses OC43 and SARS-CoV-2 in tissue culture and human airway epithelial explant cultures (HAEEC) identified four FDA-approved compounds with oral availability. Methylene blue (MB, used for the treatment of methemoglobinemia), Mycophenolic acid (MPA, used in organ transplantation) and the anti-fungal agent Posaconazole (POS) had the broadest anti-CoV spectrum. They inhibited the shedding of SARS-CoV-2 and variants-of-concern (alpha, beta, gamma, delta) from HAEEC in either pre- or post exposure regimens at clinically relevant concentrations. Co-treatment of cultured cells with MB and the FDA-approved SARS-CoV-2 RNA-polymerase inhibitor Remdesivir reduced the effective anti-viral concentrations of MB by 2-fold, and Remdesivir by 4 to 10-fold, indicated by BLISS independence synergy modelling. Neither MB, nor MPA, nor POS affected the cell delivery of SARS-CoV-2 or OC43 (+)sense RNA, but blocked subsequent viral RNA accumulation in cells. Unlike Remdesivir, MB, MPA or POS did not reduce the release of viral RNA in post exposure regimen, thus indicating infection inhibition at a post-replicating step as well. In summary, the data emphasize the power of unbiased, full cycle compound screens to identify and repurpose broadly acting drugs against coronaviruses.

11.
Infection ; 50(3): 661-669, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1611526

ABSTRACT

BACKGROUND: Sequelae of COVID-19 can be severe and longlasting. We compared frequencies of fatigue, depression and cognitive dysfunction in survivors of SARS-CoV-2-infection and sepsis. METHODS: We performed a prospective cohort study of 355 symptomatic post-COVID patients who visited our out-patient clinic for post-COVID-19 care. We compared them with 272 symptomatic patients from the Mid-German Sepsis Cohort, which investigates the long-term courses of sepsis survivors. Possible predictors for frequent clinical findings (fatigue, signs of depression, cognitive dysfunction) in post-COVID were investigated with multivariable logistic regression. RESULTS: Median age of the post-COVID patients was 51 years (range 17-86), 60.0% were female, and 31.8% required hospitalization during acute COVID-19. In the post-COVID patients (median follow-up time: 163 days) and the post-sepsis patients (180 days), fatigue was found in 93.2% and 67.8%, signs of depression were found in 81.3% and 10.9%, and cognitive dysfunction was found in 23.5% and 21.3%, respectively. In post-COVID, we did not observe an association between fatigue or depression and the severity of acute COVID-19. In contrast, cognitive dysfunction was associated with hospitalization (out-patient versus in-patient) and more frequent in post-COVID patients treated on an ICU compared to the MSC patients. CONCLUSION: In post-COVID patients, fatigue and signs of depression are more common than in sepsis survivors, independent from the acute SARS-CoV-2-infection. In contrast, cognitive dysfunction is associated with hospitalization. Despite the differences in frequencies, owing to the similarity of post-COVID and post-sepsis sequelae, this knowledge may help in implementing follow-up approaches after SARS-CoV-2 infection.


Subject(s)
COVID-19 , Cognitive Dysfunction , Sepsis , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/epidemiology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Disease Progression , Fatigue/diagnosis , Fatigue/epidemiology , Fatigue/etiology , Female , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Sepsis/complications , Sepsis/epidemiology , Young Adult
12.
Front Immunol ; 12: 784989, 2021.
Article in English | MEDLINE | ID: covidwho-1603282

ABSTRACT

Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies, the transient and stress-triggered release of a sphingomyelinase, SMPD1, into circulation and subsequent ceramide generation provides a promising target for FDA-approved drugs. Here, we report the activation of sphingomyelinase-ceramide pathway in 23 intensive care patients with severe COVID-19. We observed an increase of circulating activity of sphingomyelinase with subsequent derangement of sphingolipids in serum lipoproteins and from red blood cells (RBC). Consistent with increased ceramide levels derived from the inert membrane constituent sphingomyelin, increased activity of acid sphingomyelinase (ASM) accurately distinguished the patient cohort undergoing intensive care from healthy controls. Positive correlational analyses with biomarkers of severe clinical phenotype support the concept of an essential pathophysiological role of ASM in the course of SARS-CoV-2 infection as well as of a promising role for functional inhibition with anti-inflammatory agents in SARS-CoV-2 infection as also proposed in independent observational studies. We conclude that large-sized multicenter, interventional trials are now needed to evaluate the potential benefit of functional inhibition of this sphingomyelinase in critically ill patients with COVID-19.


Subject(s)
COVID-19/metabolism , Ceramides/metabolism , Signal Transduction , Sphingomyelin Phosphodiesterase/metabolism , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Ceramides/blood , Enzyme Activation , Erythrocyte Membrane/metabolism , Erythrocytes/metabolism , Fatty Acids/metabolism , Humans , Intensive Care Units , Patient Acuity , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Sphingomyelin Phosphodiesterase/blood , Sphingomyelins/metabolism
13.
Clin Sci (Lond) ; 135(24): 2781-2791, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1599254

ABSTRACT

Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.


Subject(s)
COVID-19/blood , COVID-19/physiopathology , Erythrocytes/metabolism , Lysophospholipids/blood , Sphingosine/analogs & derivatives , Aged , Cells, Cultured , Humans , Lipoproteins, HDL/metabolism , Phosphotransferases (Alcohol Group Acceptor)/metabolism , SARS-CoV-2 , Serum Albumin/metabolism , Sphingosine/blood
14.
Intensive Care Med Exp ; 9(1): 63, 2021 Dec 29.
Article in English | MEDLINE | ID: covidwho-1591604

ABSTRACT

In critically ill patients with sepsis, there is a grave lack of effective treatment options to address the illness-defining inappropriate host response. Currently, treatment is limited to source control and supportive care, albeit with imminent approval of immune modulating drugs for COVID-19-associated lung failure the potential of host-directed strategies appears on the horizon. We suggest expanding the concept of sepsis by incorporating infectious stress within the general stress response of the cell to define sepsis as an illness state characterized by allostatic overload and failing adaptive responses along with biotic (pathogen) and abiotic (e.g., malnutrition) environmental stress factors. This would allow conceptualizing the failing organismic responses to pathogens in sepsis with an ancient response pattern depending on the energy state of cells and organs towards other environmental stressors in general. Hence, the present review aims to decipher the heuristic value of a biological definition of sepsis as a failing stress response. These considerations may motivate a better understanding of the processes underlying "host defense failure" on the organismic, organ, cell and molecular levels.

15.
Front Psychiatry ; 12: 759694, 2021.
Article in English | MEDLINE | ID: covidwho-1581161

ABSTRACT

Background: The COVID-19 pandemic has led to an increased psychological strain on public mental health and may impact behavioral, mental, and physical health, presumably with effects on patients with severe mental disorders. This study examines pandemic-related physical and mental health and (compensatory) behavioral changes, in patients with BD as compared to healthy control individuals. Method: Physical and mental health and self-reported changes in daily structure and behavior due to the pandemic were assessed using a self-constructed questionnaire and the brief symptom inventory (BSI) in Germany, Austria, and Denmark in individuals with BD and a healthy control group. Results: The present study included 118 individuals with BD and 215 healthy controls. Individuals with BD reported statistically significant higher physical risk burden, increased weight gain, more physical comorbidities, and a decrease in physical activity and they further reported higher rates of COVID-19 testing, had more worries concerning health, and experienced more anxiety but less social distancing. Conclusion: The COVID-19 pandemic seems to have a greater impact on physical health in individuals with BD than in healthy controls. Individuals with BD appear to be having more difficulties compensating their behavior due to the pandemic which could amplify the effect of risk factors associated with poorer physical health. This highlights the necessity for optimizing and targeting the overall treatment of both mental and physical health in patients with BD during periods with far-reaching changes such as the COVID-19 pandemic. Limitations: Sampling issues and self-report forms, selectivity (missing elderly, and those lacking access or knowledge of technology).

16.
Anaesthesist ; 70(8): 673-680, 2021 Aug.
Article in German | MEDLINE | ID: covidwho-1573821

ABSTRACT

BACKGROUND: The reported mortality for sepsis and septic shock varies between 15% and 59% in international comparison. For Germany, the number of studies is limited. Previous estimations of mortality in Germany are outdated or based on claims data analyses. Various authors discuss whether lacking quality initiatives and treatment standards in Germany could cause higher mortality for sepsis. This contrasts with the internationally well-recognized performance of the German intensive care infrastructure during the COVID-19 pandemic. OBJECTIVES: The objectives of this systematic review and meta-analysis were to estimate 30-day and 90-day mortality of patients with sepsis and patients with septic shock in Germany and to compare the mortality with that of other industrialized regions (Europe, North America). MATERIAL AND METHODS: A systematic literature search included interventional and observational studies published between 2009 and 2020 in PubMed and the Cochrane Library that analyzed adult patients with sepsis, severe sepsis and septic shock in Europe and North America. Studies with less than 20 patients were excluded. The 30-day and 90-day mortality for sepsis and septic shock were pooled separately for studies conducted in Germany, Europe (excluding Germany) and North America in a meta-analysis using a random effects model. Mortality over time was analyzed in a linear regression model. RESULTS: Overall, 134 studies were included. Of these, 15 studies were identified for the estimation of mortality in Germany, covering 10,434 patients, the number of patients per study ranged from 28 to 4183 patients. The 30-day mortality for sepsis was 26.50% (95% confidence interval, CI: 19.86-33.15%) in Germany, 23.85% (95% CI: 20.49-27.21%) in Europe (excluding Germany) and 19.58% (95% CI: 14.03-25.14%) in North America. The 30-day mortality for septic shock was 30.48% (95% CI: 29.30-31.67%) in Germany, 34.57% (95% CI: 33.51-35.64%) in Europe (excluding Germany) and 33.69% (95% CI: 31.51-35.86%) in North America. The 90-day mortality for septic shock was 38.78% (95% CI: 32.70-44.86%) in Germany, 41.90% (95% CI: 38.88-44.91%) in Europe (excluding Germany) and 34.41% (95% CI: 25.66-43.16%) in North America. A comparable decreasing trend in sepsis 30-day mortality was observed in all considered regions since 2009. CONCLUSION: Our analysis does not support the notion that mortality related to sepsis and septic shock in Germany is higher in international comparison. A higher mortality would not be obvious either, since intensive care, for example also during the COVID-19 pandemic, is regarded as exemplary in Germany and the structural quality, such as the number of intensive care beds per 100,000 inhabitants, is high in international comparison. Nevertheless, deficits could also exist outside intensive care medicine. A comparison of international individual studies should take greater account of the structure of healthcare systems, the severity of disease and the limitations resulting from the data sources used.


Subject(s)
Sepsis , Shock, Septic , Adult , Germany/epidemiology , Humans , Observational Studies as Topic , Sepsis/mortality , Shock, Septic/mortality
17.
Clin Sci (Lond) ; 135(24): 2781-2791, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1559238

ABSTRACT

Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.


Subject(s)
COVID-19/blood , COVID-19/physiopathology , Erythrocytes/metabolism , Lysophospholipids/blood , Sphingosine/analogs & derivatives , Aged , Cells, Cultured , Humans , Lipoproteins, HDL/metabolism , Phosphotransferases (Alcohol Group Acceptor)/metabolism , SARS-CoV-2 , Serum Albumin/metabolism , Sphingosine/blood
18.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295556

ABSTRACT

Coronaviruses (CoVs) circulate in humans and animals, and expand their host range by zoonotic and anthroponotic transmissions. Endemic human CoVs, such as 229E and OC43 cause limited respiratory disease, and elicit short term anti-viral immunity favoring recurrent infections. Yet, severe acute respir-atory syndrome (SARS)-CoV-2 spreads across the globe with unprecedented impact on societies and economics. The world lacks broadly effective and affordable anti-viral agents to fight the pandemic and reduce the death toll. Here, we developed an image-based multicycle replication assay for focus for-mation of α-coronavirus hCoV-229E-eGFP infected cells for screening with a chemical library of 5440 compounds arrayed in 384 well format. The library contained about 39% clinically used compounds, 26% in phase I, II or III clinical trials, and 34% in preclinical development. Hits were counter-selected against toxicity, and challenged with hCoV-OC43 and SARS-CoV-2 in tissue culture and human bronchial and nasal epithelial explant cultures from healthy donors. Fifty three compounds inhibited hCoV-229E-GFP, 39 of which at 50% effective concentrations (EC50) < 2μM, and were at least 2-fold separated from toxicity. Thirty nine of the 53 compounds inhibited the replication of hCoV-OC43, while SARS-CoV-2 was inhibited by 11 compounds in at least two of four tested cell lines. Six of the 11 compounds are FDA-approved, one of which is used in mouth wash formulations, and five are systemic and orally available. Here, we demonstrate that methylene blue (MB) and mycophenolic acid (MPA), two broadly available low cost compounds, strongly inhibited shedding of infectious SARS-CoV-2 at the apical side of the cultures, in either pre- or post-exposure regimens, with somewhat weaker effects on viral RNA release indicated by RT-qPCR measurements. Our study illustrates the power of full cycle screens in repurposing clinical compounds against SARS-CoV-2. Importantly, both MB and MPA reportedly act as immunosuppressants, making them interesting candidates to counteract the cytokine storms affecting COVID-19 patients.

19.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294462

ABSTRACT

Conditional yield skewness is an important summary statistic of the state of the economy. It exhibits pronounced variation over the business cycle and with the stance of monetary policy, and a tight relationship with the slope of the yield curve. Most importantly, variation in yield skewness has substantial forecasting power for future bond excess returns, high-frequency interest rate changes around FOMC announcements, and consensus survey forecast errors for the ten-year Treasury yield. The COVID pandemic did not disrupt these relations: historically high skewness correctly anticipated the run-up in long-term Treasury yields starting in late 2020. The connection between skewness, survey forecast errors, excess returns, and departures of yields from normality is consistent with a theoretical framework where one of the agents has biased beliefs.

20.
National Bureau of Economic Research Working Paper Series ; No. 28954, 2021.
Article in English | NBER, Grey literature | ID: grc-748431

ABSTRACT

Conditional yield skewness is an important summary statistic of the state of the economy. It exhibits pronounced variation over the business cycle and with the stance of monetary policy, and a tight relationship with the slope of the yield curve. Most importantly, variation in yield skewness has substantial forecasting power for future bond excess returns, high-frequency interest rate changes around FOMC announcements, and consensus survey forecast errors for the ten-year Treasury yield. The COVID pandemic did not disrupt these relations: historically high skewness correctly anticipated the run-up in long-term Treasury yields starting in late 2020. The connection between skewness, survey forecast errors, excess returns, and departures of yields from normality is consistent with a theoretical framework where one of the agents has biased beliefs.

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