Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity (preprint)

Protein S (PS), the critical plasma cofactor for the anticoagulants tissue factor (TF) pathway inhibitor (TFPI) and activated protein C (APC), circulates in two functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP) (anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we identified a shear-dependent interaction between PS and von Willebrand Factor (VWF) by mass spectrometry. Consistently, plasma PS and VWF comigrated in both native and agarose gel electrophoresis. The PS/VWF interaction was blocked by TFPI but not APC, suggesting an interaction with the C-terminal sex hormone binding globulin (SHBG) region of PS. Microfluidic systems, mimicking arterial laminar flow or disrupted turbulent flow, demonstrated that PS stably binds VWF as VWF unfolds under turbulent flow. PS/VWF complexes also localized to platelet thrombi under laminar arterial flow. In thrombin generation-based assays, shearing plasma decreased PS activity, an effect not seen in the absence of VWF. Finally, free PS deficiency in COVID-19 patients, measured using an antibody that binds near the C4BP binding site in SHBG, correlated with changes in VWF, but not C4BP, and with thrombin generation. Our data suggest that PS binds to a shear-exposed site on VWF, thus sequestering free PS and decreasing its anticoagulant activity, which would account for the increased thrombin generation potential. As many viral infections present with free PS deficiency, elevated circulating VWF, and increased vascular shear, we propose that the PS/VWF interaction reported here is a likely contributor to virus-associated thrombotic risk.

Protective role of N-acetylcysteine and Sulodexide on endothelial cells after SARS-CoV-2 infection (preprint)

Objective: Severe acute respiratory syndrome coronavirus-2 causes hyperinflammation and activation of coagulation cascade and in the result aggravates endothelial cell dysfunction. N-acetylcysteine and Sulodexide have been found to mitigate endothelial damage. Approach and Results: The influence on coronary artery endothelial cells of serum collected after 4+/-1 months from coronavirus infection was studied. The concentrations of serum samples of interleukin 6, von Willebrand Factor, tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 were studied. The cultures with serum of patients after coronavirus infection were incubated with N-acetylocysteine and Sulodexide to estimate their potential protective role. The blood inflammato-ry parameters were increased in the group of cultures incubated with serum from patients after coronavirus infection. Supplementation of the serum from patients after coronavirus infection with N-acetylcysteine or Sulodexide reduced the synthesis of interleukin 6, von Willebrand Fac-tor. No changes in the synthesis of tissue Plasminogen Activator were observed. N-acetylcysteine reduced the synthesis of Plasminogen Activator Inhibitor-1. N-acetylcysteine and Sulodexide increased the tPA/PAI-1 ratio. Conclusion: N-acetylcysteine may have a role in reducing the myocardial injury occurring in the post-COVID-19 syndrome. Sulodexide can also play a protective role in post-COVID-19 patients.

Die Transparenz rechtlicher Verbraucherinformationen im Internet. Eine empirische Studie über die wichtigsten Stakeholder. (The Transparency of Legal Consumer Information Online. An Empirical Study of the Most Important Stakeholders) (preprint)

German Abstract: Informationspflichten sind seit Jahrzehnten ein fester Bestandteil des EU-Verbraucherrechts. Durch die stetig steigende Zahl von E-Commerce und Online-Verbraucherverträgen, nicht zuletzt infolge des Lockdown des stationären Einzelhandels während der COVID-19-Pandemie, ist die Bedeutung der Informationspflichten in den letzten Jahren weiter gewachsen. Ihre empirische Erforschung weckt jedoch Zweifel, ob diese Ausbreitung der Informationspflichten sinnvoll ist. Auch sind die Hinweise des europäischen Gesetzgebers, wie transparente Offenlegungen gegenüber Verbraucher/-innen gestaltet sein sollten lediglich auf einem sehr allgemeinen Niveau, so dass sie für konkrete Fälle nur bedingt hilfreich sind. Daher untersuchen wir in diesem Beitrag das Prinzip der Transparenz und seine Verwirklichung im europäischen Verbraucherrecht aus einer interdisziplinären Multi-Stakeholder-Perspektive. Wir stellen die Ergebnisse einer qualitativen empirischen Studie vor, in der wir 75 deutsche Stakeholder von Verbraucherinformationen im Internet befragt haben und geben einen Überblick über die wichtigsten Auffassungen von Richter/-innen, Anwält/-innen, Vertreter/-innen von Verbraucherorganisationen, Politiker/-innen, Unternehmer/-innen und Verbraucher/-innen. Auf dieser Grundlage entwickeln wir empirisch begründete Empfehlungen zur Verbesserung der Transparenz von Verbraucherinformationen im Internet.English Abstract: Information obligations have been an integral part of EU consumer law for decades. Due to the steadily increasing number of e-commerce and online consumer contracts, the importance of information duties has continued to grow in recent years. However, empirical research results raise doubts as to whether this proliferation of information obligations makes sense. Furthermore, the European Commission’s guidance on how disclosures to consumers should be designed to count as transparent is only on a very general level. Thus, it is only of limited help for concrete cases. In this paper we examine the principle of transparency and its realization in European consumer contract law from an interdisciplinary multi-stakeholder perspective. We present the results of a qualitative empirical study in which we interviewed 75 German stakeholders of consumer information on the internet. We give an overview of the most important views of judges, lawyers, representatives of consumer organizations, politicians, entrepreneurs and consumers. On this basis, we develop empirically based recommendations for improving the transparency of online consumer information.

Symptom Burden, Coagulopathy and Heart Disease after Acute SARS- CoV-2 Infection in Primary Practice - Results from the Study of HEarT DiseAse and ImmuNiTy After COVID-19 in Ireland (SETANTA) (preprint)

Purpose: The aim of SETANTA (Study of HEarT DiseAse and ImmuNiTy After COVID-19 in Ireland) study was to investigate symptom burden and incidence of cardiac abnormalities after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 and correlate these results with immunological response and biomarkers of coagulation.  Methods: SETANTA was a prospective, single-arm observational cross-sectional study in a primary practice setting, prospectively registered with ClinicalTrials.gov identifier: NCT04823182. Patients with recent COVID-19 infection ≥6 weeks and ≤12 months before enrolment were enrolled. Primary outcomes of interest were markers of cardiac injury detected by cardiac magnetic resonance imaging (MRI), including left ventricular ejection fraction, late gadolinium enhancement and pericardial abnormalities, and serum biomarker levels. Results: 100 patients (n= 129 approached) were included, 64% were female. Mean age was 45.2 years. The median (interquartile range) time interval between COVID-19 infection and enrolment was 189 [125, 246] days. 83% had at least one persistent symptom. 96% had positive serology for prior SARS-CoV-2 infection. Late gadolinium enhancement, pericardial effusion, was present in 2.2% and 8.3% respectively; left ventricular ejection fraction was below the normal reference limit in 17.4% of patients. Von Willebrand factor antigen was elevated in 32.7% of patients. Fibrinogen and D-Dimer levels were raised in 10.2% and 11.1% of patients, respectively.  Conclusion: In a cohort of primary practice patients recently recovered from SARS-CoV-2 infection, prevalence of persistent symptoms and markers of abnormal coagulation were high, despite a lower frequency of abnormalities on cardiac MRI compared with prior reports of patients assessed in a hospital setting.  Trial Registration: Clinicaltrials.gov, NCT04823182 (prospectively registered on 30th March 2021)

Prolonged Elevations of Factor VIII and von Willebrand Factor Antigen After Multisystem Inflammatory Syndrome in Children.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a late systemic inflammatory response to a recent mild or asymptomatic coronavirus disease of 2019 infection. The pathophysiology is incompletely understood but it often features significant coagulopathy along with cardiac and endothelial dysfunction. Endothelial inflammation has been primarily described in acute coronavirus disease of 2019 infection, with less characterization in MIS-C. Here we describe novel findings of nearly universal severe and prolonged factor VIII (FVIII) and von Willebrand factor antigen elevations in an institutional cohort of patients with MIS-C ages younger than or 21 years old (N=31). All patients had elevated acute phase reactants and D-dimer at presentation and met published criteria for MIS-C. FVIII was high at presentation in 97% of patients but continued to rise during the ensuing weeks of treatment to a mean 429%, peaking on median day 17 of illness as an outpatient. FVIII levels were >600% in multiple patients. von Willebrand factor antigen was measured less frequently but showed similar trends. These escalations occurred amidst resolving cardiac dysfunction and acute phase reactant normalization and despite patients receiving multimodal anti-inflammatory treatments and aspirin and enoxaparin thromboprophylaxis. No thrombotic events occurred. Endothelial dysfunction represented by very elevated FVIII levels may persist longer than other acute phase reactants may reflect.

Acquired Von Willebrand Syndrome following a SARS-CoV2 Infection.

Acquired von Willebrand syndrome is a rare clinical entity with approximately 700 cases described in the literature. Different etiologies can be responsible for the occurrence of this condition, including mainly lymphoproliferative and myeloproliferative syndromes, as well as cardiac diseases. Several mechanisms have been implicated depending on the etiology. Viral infections are an extremely rare cause, with only one case reported after an Epstein-Barr virus infection. In this case report, we have described the very likely association between SARS-CoV2 infection and the development of a time-limited acquired von Willebrand syndrome.

Successful use of lenalidomide to treat refractory acquired von Willebrand disease associated with monoclonal gammopathy.

Acquired von Willebrand syndrome (AVWS) is a rare hematologic disorder characterized by quantitative or qualitative defects of von Willebrand factor (vWF), a protein crucial for normal hemostasis. AVWS has been described in association with several pathologic entities with varied mechanisms. Among these, lymphoproliferative disorders are the most common, with monoclonal gammopathy of undetermined significance (MGUS) being the most frequently reported. AVWS in this setting is commonly associated with the development of bleeding that is clinically challenging to manage due to accelerated clearance of vWF, limiting the utility of many conventional treatment modalities such as DDAVP or vWF/FVIII. We report a case of a 43-year-old male who was sent to our institution for new-onset easy bruising and laboratories concerning for von Willebrand disease (vWD). Further diagnostic workup revealed evidence of an IgG monoclonal gammopathy and findings suggestive of vWF inhibition. Ultimately, he was found to have monoclonal gammopathy of clinical significance (MGCS)-associated AVWS refractory to conventional treatment but responsive to lenalidomide and dexamethasone. This case suggests that lenalidomide may be suitable for patients with AVWS secondary to MGCS.

Regulation of VWF (Von Willebrand Factor) in Inflammatory Thrombosis.

Increasing evidence indicates that inflammation promotes thrombosis via a VWF (von Willebrand factor)-mediated mechanism. VWF plays an essential role in maintaining the balance between blood coagulation and bleeding, and inflammation can lead to aberrant regulation. VWF is regulated on a transcriptional and (post-)translational level, and its secretion into the circulation captures platelets upon endothelial activation. The significant progress that has been made in understanding transcriptional and translational regulation of VWF is described in this review. First, we describe how VWF is regulated at the transcriptional and post-translational level with a specific focus on the influence of inflammatory and immune responses. Next, we describe how changes in regulation are linked with various cardiovascular diseases. Recent insights from clinical diseases provide evidence for direct molecular links between inflammation and thrombosis, including atherosclerosis, chronic thromboembolic pulmonary hypertension, and COVID-19. Finally, we will briefly describe clinical implications for antithrombotic treatment.

Increased levels of inflammatory molecules in blood of Long COVID patients point to thrombotic endotheliitis (preprint)

The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of Von Willebrand Factor, platelet factor 4, serum amyloid A, alpha-2-antiplasmin E-selectin, and platelet endothelial cell adhesion molecule-1, in the soluble part of the blood. It was noteworthy that the mean level of alpha-2-antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We also determined that by individually adding E-selectin and PECAM-1 to healthy blood, these molecules may indeed be involved in protein-protein interactions with plasma proteins (contributing to microclot formation) and platelet hyperactivation. This investigation was performed as a laboratory model investigation and the final exposure concentration of these molecules was chosen to mimic concentrations found in Long COVID. We conclude that presence of microclotting, together with relatively high levels of six inflammatory molecules known to be key drivers of endothelial and clotting pathology, points to thrombotic endotheliitis as a key pathological process in Long COVID. This has implications for the choice of appropriate therapeutic options in Long COVID.

Accelerated LVAD Pump Thrombosis in COVID-19 Patient: Case report and Mini review (preprint)

Coronavirus (COVID-19) infection exposes patients with heart failure to a higher risk of morbidity and mortality. In LVAD patients, one of the key problems that can lead to life-threatening low-flow or pump malfunction due to thrombus development in the inflow cannula, device body, or outflow graft, implicating hemodynamic instability, hemolysis, renal or hepatic failure, or cerebral or peripheral thromboembolism. [Endothelial protein C receptor and thrombomodulin levels are elevated along with procoagulants such as factor VIII, P-selectin, and von Willebrand factor and downregulated along with thrombomodulin as a result of the cytokine storm released by endothelial and immune cells. In general ,](#ref-0013) LVAD thrombosis has been found to occur in 2–13% of adult patients who use current continuous-flow devices. However, LVAD thrombosis due to COVID-19 is underreported and a few cases presented. We present a case of accelerated LVAD outflow thrombosis in the setting of COVID-19 infection with multiorgan failure.

A COVID Constellation: A Case of Transverse Myelitis and Acquired von Willebrand Syndrome.

The coronavirus disease 2019 (COVID-19) pandemic revealed a myriad of postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequelae, many of which remain poorly understood. We describe a rare presentation of a patient developing 2 simultaneous COVID-19 sequelae: transverse myelitis and acquired von Willebrand syndrome (AVWS). There have been numerous published case reports of patients developing transverse myelitis after a diagnosis of COVID-19. However, none have described AVWS as an observed complication from SARS-CoV-2 infection. To our knowledge, this case report is the first to describe AVWS as a result of COVID-19 infection, suggesting that patients with a prior diagnosis of COVID-19 are susceptible to developing this rare bleeding disorder.

High levels of von Willebrand factor with reduced specific activities in hospitalized patients with or without COVID-19.

The COVID-19 pandemic is often accompanied by severe respiratory illness and thrombotic complications. Von Willebrand Factor (VWF) levels are highly elevated in this condition. However, limited data are available on the qualitative activity of VWF in COVID-19. We measured plasma VWF levels quantitatively (VWF antigen) and qualitatively (ristocetin-induced platelet agglutination, glycoprotein IbM (GPIbM) binding, and collagen binding). Consistent with prior reports, VWF antigen levels were significantly elevated in hospitalized patients with or without COVID-19. The GPIbM and collagen binding activity-to-antigen ratios were significantly reduced, consistent with qualitative changes in VWF in COVID-19. Of note, critically ill hospitalized patients without COVID-19 had similar reductions in VWF activity-to-antigen ratios as patients with COVID-19. Our data suggest that qualitative changes in VWF in COVID-19 may not be specific to COVID-19. Future studies are warranted to determine the mechanisms responsible for qualitative changes in VWF in COVID-19 and other critical illnesses.• VWF levels were increased in COVID-19 compared to healthy controls.• VWF activity-to-antigen ratios were decreased in COVID-19 compared to healthy controls.• There were no differences in VWF activity-to-antigen ratios between hospitalized patients with or without COVID-19.• These findings are consistent with qualitative changes in VWF in systemic inflammation which are not specific to COVID-19.• Future studies are needed to define possible roles of changes in conformation or multimer length in the qualitative changes in VWF in systemic inflammation.

von Willebrand disease and von Willebrand factor.

Progress in both basic and translational research into the molecular mechanisms of VWD can be seen in multiple fields. GENETICS OF VWD: In the past several decades, knowledge of the underlying pathogenesis of von Willebrand disease (VWD) has increased tremendously, thanks in no small part to detailed genetic mapping of the von Willebrand Factor (VWF) gene and advances in genetic and bioinformatic technology. However, these advances do not always easily translate into improved management for patients with VWD and low-VWF levels. VWD AND PREGNANCY: For example, the treatment of pregnant women with VWD both pre- and postpartum can be complicated. While knowledge of the VWF genotype at some amino acid positions can aid in knowledge of who may be at increased risk of thrombocytopenia or insufficient increase in VWF levels during pregnancy, in many cases, VWF levels and bleeding severity is highly heterogeneous, making monitoring recommended during pregnancy to optimize treatment strategies. VWF AND COVID-19: New challenges related to the consequences of dysregulation of hemostasis continue to be discovered. The ongoing COVID-19 pandemic has highlighted that VWF has additional biological roles in the regulation of inflammatory disorders and angiogenesis, disruption of which may contribute to COVID-19 induced vasculopathy. Increased endothelial cell activation and Weibel-Palade body exocytosis in severe COVID-19 lead to markedly increased plasma VWF levels. Coupled with impairment of normal ADAMTS13 multimer regulation, these data suggest a role for VWF in the pathogenesis underlying pulmonary microvascular angiopathy in severe COVID-19. CONCLUSION: With the increased affordability and availability of next-generation sequencing techniques, as well as a push towards a multi-omic approach and personalized medicine in human genetics, there is hope that translational research will improve VWD patient outcomes.

Acquired Thrombotic Thrombocytopenic Purpura following inactivated COVID 19 vaccines: Two case-reports and a short literature review (preprint)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak from December 2019 causing millions of deaths all over the world and the lack of specific treatment for severe forms of coronavirus disease 2019 (COVID-19) has led to vaccines development in record time with emergency use authorization in several countries increasing the risk of vaccine safety issues. Recently, several cases of Thrombotic Thrombocytopenic Purpura (TTP) have been reported following COVID-19 vaccination. TTP represents a life-threatening consumptive coagulopathy requiring urgent diagnosis and prompt treatment. It is a rare disease characterized by thrombocytopenia, microangiopathic hemolytic anemia and ischemic end-organ lesions. It can be either congenital or acquired. Various events such viral infections, medication, pregnancy, malignancies, and vaccinations may cause TTP. Clinicians should consider this diagnosis when evaluating thrombocytopenia in the post-vaccine period. Here, we report two cases of acquired TTP following Sinopharm COVID-19 vaccine (BBIBP-CorV) and Sinovac COVID-19 vaccine (CoronaVac). Diagnosis was based on clinical presentation and confirmed with severe reduction in the activity of von Willebrand factor-cleaving protease ADAMTS-13 and the presence of inhibitory autoantibodies. The two patients were successfully treated with corticosteroids, plasma exchange therapy and rituximab in the acute phase. In the literature, the reported cases of TTP induced by COVID-19 vaccination occurred after Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based COVID-19 Vaccines. To the best of our knowledge, this is the first report of acquired TTP after inactivated virus COVID-19 vaccines. A short literature review regarding acquired TTP patients following COVID-19 vaccines is also included.

Acquired von Willebrand Syndrome and Desmopressin Resistance During Venovenous Extracorporeal Membrane Oxygenation in Patients With COVID-19: A Prospective Observational Study.

OBJECTIVES: Although COVID-19 is associated with high von Willebrand factor (vWF) parameters promoting thrombosis, venovenous extracorporeal membrane oxygenation (vvECMO) is associated with the development of acquired von Willebrand syndrome (AVWS) promoting bleeding. This study was designed to assess both the incidence and severity of AVWS in COVID-19 patients undergoing vvECMO, and the benefit of comprehensive vWF analyses. DESIGN: Prospective observational study. SETTING: ICU at a tertiary-care center. PATIENTS: Twenty-seven consecutive COVID-19 patients with acute respiratory distress syndrome (ARDS) requiring vvECMO. MEASUREMENTS AND MAIN RESULTS: Comprehensive vWF analyses (including sodium dodecyl-sulfate polyacrylamide gel electrophoresis) were performed before, during, and after vvECMO. In a subgroup of 12 patients with AVWS, effectiveness of treatment with desmopressin was assessed. The patients' mean age was 53 years (range, 23-73), 70% were male, and all had various comorbidities. Following markedly elevated vwf antigen (vWF: Ag; mean, 546% ( sd , 282]), vWF collagen binding capacity (mean, 469% [ sd , 271]), vWF activity (vWF:A; mean, 383% [ sd , 132]), and factor VIII activity (mean, 302% [ sd , 106]), and only borderline decreases in high-molecular-weight (HMW) vWF multimers before vvECMO, all of these variables decreased and HMW vWF multimers became undetectable within hours following initiation of vvECMO. All variables fully recovered within 3-38 hours after discontinuation of vvECMO. During vvECMO, decreases in the vWF:A/vWF:Ag ratio correlated with absent HMW vWF multimers. Desmopressin did not affect vWF parameters. CONCLUSIONS: In patients with COVID-19-associated ARDS, AVWS developed soon after initiation of vvECMO. The vWF:A/vWF:Ag ratio was a suitable screening test for AVWS. As desmopressin was ineffective, bleeding during vvECMO-associated AVWS should preferably be treated with concentrates containing vWF.

Krebs von den Lungen 6 levels in COVID-19 ICU Patients are Associated with Mortality (preprint)

Rationale Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Elevated circulating levels of KL-6 may denote disorder of the alveolar epithelial lining. Objective Aim of this study was to verify if KL-6 values may help to risk stratify and triage severe COVID-19 patients. Methods We performed a retrospective prognostic study on 110 COVID-19 ICU patients, evaluating the predictive role of KL-6 for mortality. Measurements and Main Results The study sample was divided in two groups related according to the median KL-6 value [Group A (KL-6 lower than the log-transformed median (6.73)) and Group B (KL-6 higher than the log-transformed median)]. In both linear and logistic multivariate analyses, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) was significantly and inversely related to KL-6. Death rate was higher in group B than in group A (80.3 versus 45.9%) (p<0.001), Accordingly, the Cox regression analysis showed a significant prognostic role of KL-6 on mortality in the whole sample as well as in the subgroup with SOFA lower than its median value. Conclusions At ICU admission, KL-6 serum level was significantly lower in the survivors group. Our findings shown that, in severe COVID19 patients, elevated KL-6 was strongly associated with mortality in ICU.

The impact of digitalization on poverty alleviation in Africa (preprint)

ABSTRACT & RÉSUMÉ & ZUSAMMENFASSUNG : Digitalization in Sub-Saharan Africa enhanced the accessibility of communications by the majority of the poor who had been excluded among others from social media, independent information channels, mobile banking and e-commerce. The creation of new economic opportunities, e.g. the pay-as-you-go business, and increased flow of information also boosted people’s self-esteem, sense of belonging and citizenship. The smartphone became the main source of internet access which also bridged the divide between urban and rural communities. Thus, mobile telecommunications contributed positively to economic growth even in less developed regions, and there is apparently still ample space for further improvement. Yet, Africans were also confronted with new forms of the digital divide between the poor and the rich, between advanced and less advanced African countries, as well as between Africa and the rest of the world. Moreover, the digitalization of the public sphere became a double-edged sword. Autocratic governments like Sudan and Togo shut down the internet during elections to facilitate the rigging of the polls. The lack of transparency and objectivity fuelled fake news which rapidly spread in social media, notably in times of the Corona crisis. Last, but not least, not everybody surfing in the internet had the same access to quality information. For example, disinformation was supported clandestinely by foreign powers to destabilize political regimes, or spy software was provided to governments to control the opposition. Both false news in social media and spy-software impeded poverty relieve in Africa significantly. ----------------------------------------------------------------------------------------------------------------------------------------------------- RÉSUMÉ : La numérisation en Afrique subsaharienne a amélioré l'accessibilité des communications par la majorité des pauvres qui avaient été exclus, entre autres, des médias sociaux, des canaux d'information indépendants, des services bancaires mobiles et du commerce électronique. La création de nouvelles opportunités économiques, par ex. l'activité par répartition et l'augmentation du flux d'informations, ont également renforcé l'estime de soi des personnes, leur sentiment d'appartenance et de citoyenneté. Le smartphone est devenu la principale source d'accès à Internet, ce qui a également permis de combler le fossé entre les communautés urbaines et rurales. Ainsi, les télécommunications mobiles ont contribué positivement à la croissance économique, même dans les régions les moins développées, et il y a apparemment encore amplement de place pour de nouvelles améliorations. Pourtant, les Africains ont également été confrontés à de nouvelles formes fossé digital entre les pauvres et les riches, entre les pays africains avancés et moins avancés, ainsi qu'entre l'Afrique et le reste du monde. De plus, la numérisation de la sphère publique est devenue une arme à double tranchant. Des gouvernements autocratiques, comme le Soudan et le Togo, ont fermé Internet pendant les élections pour faciliter le trucage des élections. De plus, le manque de transparence et d'objectivité a alimenté les fausses informations qui se sont rapidement propagées sur les réseaux sociaux, notamment en période de crise de COVID-19. Enfin, tout le monde qui navigue sur Internet n'a pas le même accès à des informations de qualité. La désinformation était soutenue clandestinement par des puissances étrangères pour déstabiliser les régimes politiques, ou des logiciels espions fournis aux gouvernements pour contrôler l'opposition. Les fausses nouvelles dans les médias sociaux et les logiciels espions ont entravé la pauvreté en Afrique de manière significative. ----------------------------------------------------------------------------------------------------------------------------------------------------------- ZUSAMMENFASSUNG : Die Digitalisierung in Subsahara-Afrika verbesserte Kommunikations-Zugang für die Mehrheit der Armen, die bis dahin unter anderem von sozialen Medien, unabhängigen Informationskanälen, Mobile Banking und E-Commerce ausgeschlossen waren. Die Schaffung neuer wirtschaftlicher Möglichkeiten, z.B. das Umlageverfahren und der verstärkte Informationsfluss, stärkten auch das Selbstwertgefühl, das Zugehörigkeitsgefühl und das Nationalbewußtsein der Menschen. Das Smartphone wurde zur Hauptquelle des Internetzugangs, der auch die Kluft zwischen urbanen und ländlichen Gebieten überbrückte. Damit trug der Mobilfunk auch in weniger entwickelten Regionen positiv zum Wirtschaftswachstum bei, und es gibt offenbar noch viel Raum für weitere Verbesserungen. Afrikaner wurden aber auch mit neuen Formen der digitalen Kluft zwischen Arm und Reich, zwischen entwickelten und weniger entwickelten afrikanischen Ländern sowie zwischen Afrika und dem Rest der Welt konfrontiert. Zudem wurde die Digitalisierung der Öffentlichkeit zu einem zweischneidigen Schwert. Autokratische Regierungen wie der Sudan und Togo haben das Internet beispielsweise während der Wahlen abgeschaltet, um Wahlfälschung zu erleichtern. Zudem befeuerte der Mangel an Transparenz und Objektivität insbesondere in Zeiten der Corona-Krise fake news, die sich in den sozialen Medien rasant verbreiteten. Nicht zuletzt hatte nicht jeder, der im Internet surfte, den gleichen Zugang zu qualitativ hochwertigen Informationen. Desinformation wurde zudem oft heimlich von ausländischen Mächten unterstützt, um politische Regime zu destabilisieren, oder den Regierungen Spionagesoftware zur Verfügung gestellt, um die Opposition zu kontrollieren. Sowohl Desinformation in sozialen Medien als auch Spionagesoftware haben die Armutsbekämpfung in Afrika erheblich behindert.

Plasma biomarkers associated with survival and thrombosis in hospitalized COVID-19 patients (preprint)

Severe coronavirus disease-19 (COVID-19) has been associated with fibrin-mediated hypercoagulability and thromboembolic complications. To evaluate potential biomarkers of coagulopathy and disease severity in COVID-19, we measured plasma levels of eight biomarkers potentially associated with coagulation, fibrinolysis, and platelet function in 43 controls and 63 COVID-19 patients, including 47 patients admitted to the intensive care unit (ICU) and 16 non-ICU patients. COVID-19 patients showed significantly elevated levels of fibrinogen, tissue plasminogen activator (t-PA), and its inhibitor plasminogen activation inhibitor 1 (PAI-1), as well as ST2 (the receptor for interleukin 33) and von Willebrand factor (vWF) compared to the control group. We found that higher levels of t-PA, ST2, and vWF at the time of admission were associated with lower survival rates, and that thrombotic events were more frequent in patients with initial higher levels of vWF. These results support a predictive role of specific biomarkers such as t-PA and vWF in the pathophysiology of COVID-19. The data provide support for the case that hypercoagulability in COVID-19 is fibrin-mediated, but also highlights the important role that vWF may play in the genesis of thromboses in the pathophysiology of COVID-19. Interventions designed to enhance fibrinolysis and reduce platelet aggregation might prove to be useful adjuncts in the treatment of coagulopathy in a subset of COVID-19 patients.