The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population-A comparison of two German registries.

Objectives: To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared. Methods: 4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total. Results: Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19. Conclusion: Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease.

Convalescent plasma treatment for SARS-CoV-2 infected high-risk patients: a matched pair analysis to the LEOSS cohort.

Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma (CP) has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. We performed a retrospective analysis of 55 hospitalized COVID-19 patients from University Hospital Duesseldorf (UKD) at high risk for disease progression, in a substantial proportion due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with CP. Both cohorts had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality: UKD 60.9%, LEOSS 48.3%. In our cohort of COVID-19 patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched-pairs analysis. However, our data supports the concept that a reduction in mortality is achievable by early CP administration.

COVID-19 Severity and Thrombo-Inflammatory Response Linked to Ethnicity.

Although there is strong evidence that SARS-CoV-2 infection is associated with adverse outcomes in certain ethnic groups, the association of disease severity and risk factors such as comorbidities and biomarkers with racial disparities remains undefined. This retrospective study between March 2020 and February 2021 explores COVID-19 risk factors as predictors for patients' disease progression through country comparison. Disease severity predictors in Germany and Japan were cardiovascular-associated comorbidities, dementia, and age. We adjusted age, sex, body mass index, and history of cardiovascular disease comorbidity in the country cohorts using a propensity score matching (PSM) technique to reduce the influence of differences in sample size and the surprisingly young, lean Japanese cohort. Analysis of the 170 PSM pairs confirmed that 65.29% of German and 85.29% of Japanese patients were in the uncomplicated phase. More German than Japanese patients were admitted in the complicated and critical phase. Ethnic differences were identified in patients without cardiovascular comorbidities. Japanese patients in the uncomplicated phase presented a suppressed inflammatory response and coagulopathy with hypocoagulation. In contrast, German patients exhibited a hyperactive inflammatory response and coagulopathy with hypercoagulation. These differences were less pronounced in patients in the complicated phase or with cardiovascular diseases. Coagulation/fibrinolysis-associated biomarkers rather than inflammatory-related biomarkers predicted disease severity in patients with cardiovascular comorbidities: platelet counts were associated with severe illness in German patients. In contrast, high D-dimer and fibrinogen levels predicted disease severity in Japanese patients. Our comparative study indicates that ethnicity influences COVID-19-associated biomarker expression linked to the inflammatory and coagulation (thrombo-inflammatory) response. Future studies will be necessary to determine whether these differences contributed to the less severe disease progression observed in Japanese COVID-19 patients compared with those in Germany.

SARS-CoV-2 Vaccination Rate and SARS-CoV-2 Infection of Health Care Workers in Aerosol-Generating Medical Disciplines.

Healthcare workers (HCW) who perform aerosol-generating procedures (AGP) are at high risk of SARS-CoV-2 infection. Data on infection rates and vaccination are limited. A nationwide, cross-sectional study focusing on AGP-related specialties was conducted between 3 May 2021 and 14 June 2021. Vaccination rates among HCW, perception of infection risk, and infection rates were analyzed, focusing on the comparison of gastrointestinal endoscopy (GIE) and other AGP-related specialties (NON-GIE), from the beginning of the pandemic until the time point of the study. Infections rates among HCW developed similarly to the general population during the course of the pandemic, however, with significantly higher infections rates among the GIE specialty. The perceived risk of infection was distributed similarly among HCW in GIE and NON-GIE (91.7%, CI: 88.6−94.4 vs. 85.8%, CI: 82.4−89.0; p < 0.01) with strongest perceived threats posed by AGPs (90.8%) and close patient contact (70.1%). The very high vaccination rate (100−80%) among physicians was reported at 83.5%, being significantly more frequently reported than among nurses (56.4%, p < 0.01). GIE had more often stated very high vaccination rate compared with NON-GIE (76.1% vs. 65.3%, p < 0.01). A significantly higher rate of GIE was reported to have fewer concerns regarding infection risk after vaccination than NON-GIE (92.0% vs. 80.3%, p < 0.01).

Corrigendum to "Machine Learning Based Prediction of COVID-19 Mortality Suggests Repositioning of Anticancer Drug for Treating Severe Cases"[Artificial Intelligence in Life Sciences] 1(2021), 100020.

[This corrects the article DOI: 10.1016/j.ailsci.2021.100020.].

Underwater vs Conventional Endoscopic Mucosal Resection of Large Sessile or Flat Colorectal Polyps: A Prospective Randomized Controlled Trial.

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (CEMR) with submucosal injection is the current standard for the resection of large, nonmalignant colorectal polyps. We investigated whether underwater endoscopic mucosal resection (UEMR) is superior to CEMR for large (20-40mm) sessile or flat colorectal polyps. METHODS: In this prospective randomized controlled study, patients with sessile or flat colorectal polyps between 20 and 40 mm in size were randomly assigned to UEMR or CEMR. The primary outcome was the recurrence rate after 6 months. Secondary outcomes included en bloc and R0 resection rates, number of resected pieces, procedure time, and adverse events. RESULTS: En bloc resection rates were 33.3% in the UEMR group and 18.4% in the CEMR group (P = .045); R0 resection rates were 32.1% and 15.8% for UEMR vs CEMR, respectively (P = .025). UEMR was performed with significantly fewer pieces compared to CEMR (2 pieces: 45.5% UEMR vs 17.7% CEMR; P = .001). The overall recurrence rate did not differ between both groups (P = .253); however, subgroup analysis showed a significant difference in favor of UEMR for lesions of >30 mm to ≤40 mm in size (P = .031). The resection time was significantly shorter in the UEMR group (8 vs 14 minutes; P < .001). Adverse events did not differ between both groups (P = .611). CONCLUSIONS: UEMR is superior to CEMR regarding en bloc resection, R0 resection, and procedure time for large colorectal lesions and shows significantly lower recurrence rates for lesions >30 mm to ≤40 mm in size. UEMR should be considered for the endoscopic resection of large colorectal polyps.

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

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 Alzheimer's 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.

Impact of the COVID-19 outbreak on endoscopy training in a tertiary care centre in Germany.

OBJECTIVE: The COVID-19 crisis has impacted on all aspects of health care including medical education and training. We describe the disruption of endoscopy training in a tertiary care center in Germany. DESIGN/METHOD: The reorganization of a high-volume endoscopy unit during the German COVID-19 outbreak is described with special focus on endoscopy trainees. Changes in case volume of gastroenterology fellows were evaluated and compared to a year prior to the outbreak. RESULTS: Reallocation of resources led to the transfer of gastroenterology fellows to intensive care and infectious disease units. Case volume of fellows declined between January and April 2020 by up to 63%. When compared with data from the year prior to the outbreak, endoscopy performed by fellows reduced by up to 56%. Educational meetings and skill evaluation were cancelled indefinitely. CONCLUSION: The COVID-19 outbreak has had a negative impact on endoscopy training of gastroenterology fellows in a high-volume center in Germany. This must be taken into consideration when planning "return-strategies" after the pandemic.