ABSTRACT
From the start of the COVID-19 pandemic in Germany, different groups have been protesting measures implemented by different government bodies in Germany to control the pandemic. It was widely claimed that many of the offline and online protests were driven by conspiracy narratives disseminated through groups and channels on the messenger app Telegram. We investigate this claim by measuring the frequency of conspiracy narratives in messages from open Telegram chat groups of the Querdenken movement, set up to organize protests against COVID-19 restrictions in Germany. We furthermore explore the content of these messages using topic modelling. To this end, we collected 822k text messages sent between April 2020 and May 2022 in 34 chat groups. By fine-tuning a Distilbert model, using self-annotated data, we find that 8.24% of the sent messages contain signs of conspiracy narratives. This number is not static, however, as the share of conspiracy messages grew while the overall number of messages shows a downward trend since its peak at the end of 2020. We further find a mix of known conspiracy narratives make up the topics in our topic model. Our findings suggest that the Querdenken movement is getting smaller over time, but its remaining members focus even more on conspiracy narratives. © 2022 Association for Computational Linguistics.
ABSTRACT
Background. Patients with hematological malignancy or other cancers as well as immunosuppression bear a high risk for severe COVID-19. Monoclonal antibodies (mAb) are efficient at early stages of the disease but may lose potency with new variants. Trials on plasma from convalescent donors in unselected patients have not shown clinical benefit. No randomized trials focussing on patients with underlying disease have been published. Methods. We conducted an open-label, multicenter, randomized controlled trial to evaluate efficacy of plasma (CVP - convalescent or after vaccination) in patients with COVID-19 at high risk for adverse outcome in Germany. We assessed the effect of high-titer CVP (2 units from different donors, 238-337 ml each, on subsequent days). Patients with hematological or other malignancy (group 1), immunosuppression (group 2), age >50 and <=75 years and lymphopenia and/or high D-dimers (group 3) or age >75 years (group 4) who were hospitalized with confirmed SARS-CoV-2 infection and with an oxygen saturation <=94% were included. Primary outcome measure was time to clinical improvement on a seven-point ordinal scale, secondary outcome was mortality (Janssen et al. Trials 2020 Oct 6;21(1):828). Results. Overall, 133 patients were randomized, 68 received CVP with an additional 10 patients as a crossover on day 10. Median age (range) was 68 years (39-95) in the CVP group and 70 (38-90) in controls. For the entire cohort, no significant difference was seen in time to improvement (median days: CVP 12.5 vs. control 18;HR 1.24 (95% confidence interval (CI) 0.83-1.85), p=0.29). Subgroup analysis (group 1+2) revealed shortened time to improvement (median days CVP 13 vs. control 32;HR 2.03 (95%CI 1.17-3.6), p=0.01) and mortality was reduced (mortality CVP n=6 (18%) vs. control n=10 (29%). No significant differences in time to improvement were observed in group 3 or 4 (HR 0.72 (95%CI 0.41-1.28), p=0.26). No relevant adverse events were observed. Conclusion. CVP improves time to clinical improvement and mortality for COVID-19 patients with underlying hematological disease/cancer or other reasons of impaired immune response. Even with new variants, high-titer CVP may offer a widely available and inexpensive therapy option in high-risk groups. Funding. BMBF FKZ 01KI20152;EudraCT 2020-001632-10.
ABSTRACT
Background: Therapy options are limited for COVID-19 patients with hematological disease, cancer, immunosuppression or adanced age. Een though no benefit was obsered for conalescent plasma in unselected patients with COVID-19, retrospectie data suggest that it could be effectie in patients unable to mount a sufficient immune response upon SARS-CoV-2 infection. Plasma from accinated donors has not been systematically assessed for COVID-19 treatment. Aims: We conducted a randomized clinical trial to address plasma efficacy in patients at high risk for an aderse outcome. Methods: COVID-19 patients with confirmed SARS-CoV-2 infections and oxygen saturation <=94% were randomized (NCT05200754). Patients receied conalescent or accinated SARS-CoV-2 plasma in two bags (238 - 337 ml plasma each) from different donors on day 1 and 2 (PLASMA) or standard of care (CONTROL). Randomization was stratified according to four clinical patient groups, hematological/solid cancer (group-1), treatment or disease associated immunosuppression (group 2), high risk disease by standard parameters (group-3) or age >=75 years (group-4). Mechanically entilated patients were not eligible. Plasma was obtained from donors with high leel neutralizing actiity (titer >=1:80) either after SARS-CoV-2 infection (conalescent) or after accination with at least two doses of mRNA accines (accinated). Crossoer for the control group was allowed at day 10. The primary endpoint was time to improement as two points on a seen-point ordinal scale or lie discharge from the Hospital (IMPROVEMENT) with prespecified analyses of subgroups (Janssen M, et al. Trials 2020 Oct 6;21(1):828). Results: A total of 133 patients were randomized with 68 receiing PLASMA with a median age of 68 years (range 36-95) or CONTROL (n=65, of which n=10 (15.4%) crossed oer at day 10) with a median age of 70 years (range 38-90). The distribution of the four predefined groups was group-1, n=53;group-2, n=18;group-3, n=35;and group-4, n=27. The intention to treat analysis reealed a non-significant shorter time to IMPROVEMENT for patients in PLASMA (median 12.5 days, 95%-CI [10;16]) compared to patients in CONTROL (median 18 days, 95%-CI [11;28] ), hazard ratio 1.24, 95% confidence interal [0.83;1.85], p=0.29). Oerall, 27 patients died (PLASMA, n=12;CONTROL, n=15;p=0.80). Predefined subgroup analysis reealed a clinically significant benefit in patients with hematological malignancies, other cancers or immunosuppression (group-1, group-2, n=71). With a median time to improement of 13 days (95%-CI [9;19]) for PLASMA and 32 days (95%-CI [17;57]) for CONTROL(HR 2.03, 95%-CI [1.17;3.6], p=0.01). A sensitiity analysis reealed that IMPROVEMENT appeared to be seen een earlier with accinated (median 10 days, 95%-CI [8;14]) compared to conalescent SARS-CoV-2 plasma (median 13 days, 95%-CI [6;38]) and CONTROL. Within group-1 and group-2, six patients in PLASMA (18.2%) and 10 in CONTROL (28.6%) died. No significant differences in improement were obsered in group-3 and group-4 with a HR of 0.72 (95%-CI [0.41;1.28], p=0.26). Within group-3 and group-4, six patients in PLASMA (18.8%) and fie in CONTROL (16.7%) died. No preiously unknown side effects of plasma therapy emerged within the trial. Summary/Conclusion: Plasma from conalescent and particularly accinated donors improed outcome of COVID-19 patients with an underlying hematological disease /cancer or other reasons of impaired immune response. Plasma did not improe outcome in immune-competent patients with other risk factors and/or older age. (Figure Presented).
ABSTRACT
Since the eruption of the worldwide SARS-CoV-2 pandemic in late 2019/early 2020, multiple elective surgical interventions were postponed. Through pandemic measures, elective operation capacities were reduced in favour of intensive care treatment for critically ill SARS-CoV-2 patients. Although intermittent low-incidence infection rates allowed an increase in elective surgery, surgeons have to include long-term pulmonary and extrapulmonary complications of SARS-CoV-2 infections (especially "Long Covid") in their perioperative management considerations and risk assessment procedures. This review summarizes recent consensus statements and recommendations regarding the timepoint for surgical intervention after SARS-CoV-2 infection released by respective German societies and professional representatives including DGC/BDC (Germany Society of Surgery/Professional Association of German Surgeons e.V.) and DGAI/BDA (Germany Society of Anesthesiology and Intensive Care Medicine/Professional Association of German Anesthesiologists e.V.) within the scope of the recent literature. The current literature reveals that patients with pre- and perioperative SARS-CoV-2 infection have a dramatically deteriorated postoperative outcome. Thereby, perioperative mortality is mainly caused by pulmonary and thromboembolic complications. Notably, perioperative mortality decreases to normal values over time depending on the duration of SARS-CoV-2 infection.
Subject(s)
COVID-19 , Critical Care , Elective Surgical Procedures/adverse effects , Humans , Pandemics , SARS-CoV-2ABSTRACT
Background: The clinical spectrum of coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to critical illness and death in up to 89% of mechanically ventilated patients. Therefore, new therapeutic strategies are needed. Recent evidence suggests a multi-level inflammatory syndrome in some of the most critically ill patients with overlapping features of other hyperinflammatory or autoimmune diseases. Thus, plasma exchange (PE) has become a subject of controversy as potential therapy in these patients. Here, we report the results of the so far largest cohort of critically ill COVID-19 patients treated with PE. Methods: All critically ill COVID-19 patients treated with PE at Heidelberg University Hospital were analyzed between April and December 2020. Disease course and outcomes were compared with a standard care control group matched for age, sex, and disease severity. Changes in laboratory and clinical parameters were studied longitudinally. Kaplan-Meier and Cox regression analyses were performed. Results: In total, 28 critically ill COVID-19 patients were treated with an average of 3 PE procedures per patient. No relevant complications occurred during PE therapy. Inflammatory markers and biochemical indicators of end-organ damage and endothelial activation were significantly reduced during PE. These laboratory changes were accompanied by normalization of body temperature, improved pulmonary function, and reduced vasopressor demand. Most importantly, the laboratory and clinical improvements were maintained after the last PE. In contrast, most parameters in the control group did not improve significantly over seven days, although baseline clinical and laboratory parameters were comparable in both groups. Kaplan-Meier analysis showed improved 30-day survival in the PE group compared to the control group (67.9% vs. 42.9%, p=0.044). In a multivariable analysis, the hazard ratio for death was 0.27 (95% CI 0.11-0.68, p=0.005) with PE versus standard care. Conclusions: Our data further suggest that PE represents a potential therapeutic strategy for a subset of severe COVID-19 cases. The observed PE-related effects appear to go beyond a purely artificial improvement in blood parameters and may indicate a reversal of the complex COVID-19 immunopathology. Randomized controlled trials are urgently needed.
ABSTRACT
Introduction: The spectrum of coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to respiratory failure and death of patients. Severely affected patients may develop a cytokine storm-like clinical syndrome with multi-organ failure and a mortality rate of up to 90%. Case Description: Here we report on five COVID-19 patients with a median age of 67 years who were treated at the intensive care unit due to respiratory failure. Prophylactic antibiotic, antimycotic, and antiviral/immunomodulatory therapy was initiated in all patients upon admission. During the course of the disease, patients developed circulatory shock and persistent fever together with increased interleukin 6-levels compatible with the cytokine storm-like clinical syndrome. In addition, all patients had multi-organ failure with acute respiratory-distress syndrome (ARDS, 4 severe, 1 moderate) and acute kidney injury of at least KDIGO stage 2. A single PE with a median of 3.39 L of fresh frozen plasma was initiated in all patients followed by one additional treatment in patients 1, 3, and 5. During the PE, striking reduction of inflammatory markers C-reactive protein (-47%, P=0.0078) and interleukin 6 (-74%, P=0.0078), as well as significant reduction of ferritin (-49%, P=0.0078), LDH (-41%, P=0.0078), and D-Dimer (-47%, P=0.016) were observed. Due to circulatory shock, four patients received vasopressor treatment at the start of the PE that could be substantially reduced during treatment (-71%, P=0.031). Biochemical and clinical improvement continued over the following days together with an increase in the oxygenation index in 4 out of 5 patients. These improvements were achieved with only 1 to 2 PE, which might be a possible indication of a direct pathophysiological influence of PE on the COVID-19-associated cytokine storm-like clinical syndrome. Three of the 5 most critically ill patients are alive, while a 71-year-old male and a 76-year-old female patient died after the therapy was limited due to persistent severe ARDS. Discussion: PE improved inflammation, microcirculatory clot formation, and hypotension, thereby improving clinical outcomes. Further studies to test whether (repeated) PE can alter the course of critically ill COVID-19 patients are clearly indicated.
ABSTRACT
BACKGROUND: Clinically, coronavirus disease 2019 (COVID-19) is associated with a wide range of symptoms, which can range from mild complaints of an upper respiratory infection to life-threatening hypoxic respiratory insufficiency and multiorgan failure. OBJECTIVE: The initially identified pulmonary damage patterns, such as diffuse alveolar damage in acute lung failure, are accompanied by new findings that draw a more complex scenario. These include microvascular involvement and a wide range of associated pathologies of multiple organ systems. A back-scaling of microstructural vascular changes is possible via targeted correlation of pathological autopsy results with radiological imaging. MATERIAL AND METHODS: Radiological and pathological correlation as well as microradiological imaging to investigate microvascular involvement in fatal COVID-19. RESULTS: The cases of two COVID-19 patients are presented. Patient 1 showed a relative hypoperfusion in lung regions that did not have typical COVID-19 infiltrates; the targeted post-mortem correlation also showed subtle signs of microvascular damage even in these lung sections. Patient 2 showed both radiologically and pathologically advanced typical COVID-19 destruction of lung structures and the case illustrates the damage patterns of the blood-air barrier. The perfusion deficit of the intestinal wall shown in computed tomography of patient 2 could not ultimately clearly be microscopically attributed to intestinal microvascular damage. CONCLUSION: In addition to microvascular thrombosis, our results indicate a functional pulmonary vasodysregulation as part of the pathophysiology during the vascular phase of COVID-19. The clinical relevance of autopsies and the integration of radiological imaging findings into histopathological injury patterns must be emphasized for a better understanding of COVID-19.