Impact of age and gender on lymphocyte subset counts in patients with COVID-19.

In symptomatic patients with acute Coronavirus disease 2019 (COVID-19), lymphocytopenia is one of the most prominent laboratory findings. However, to date age and gender have not been considered in assessment of COVID-19-related cell count alterations. In this study, the impact of COVID-19 as well as age and gender on a large variety of lymphocyte subsets was analyzed in 33 COVID-19 patients and compared with cell counts in 50 healthy humans. We confirm that cell counts of total lymphocytes, B, NK, cytotoxic and helper T cells are reduced in patients with severe COVID-19, and this tendency was observed in patients with moderate COVID-19. Decreased cell counts were also found in all subsets of these cell types, except for CD4+ and CD8+ effector memory RA+ (EMRA) and terminal effector CD8+ cells. In multivariate analysis however, we show that in addition to COVID-19, there is an age-dependent reduction of total, central memory (CM), and early CD8+ cell subsets, as well as naïve, CM, and regulatory CD4+ cell subsets. Remarkably, reduced naïve CD8+ cell counts could be attributed to age alone, and not to COVID-19. By contrast, decreases in other subsets could be largely attributed to COVID-19, and only partly to age. In addition to COVID-19, male gender was a major factor influencing lower counts of CD3+ and CD4+ lymphocyte numbers. Our study confirms that cell counts of lymphocytes and their subsets are reduced in patients with COVID-19, but that age and gender must be considered when interpreting the altered cell counts.

Evaluation of a single-use gastroscope in patients presenting with suspected upper gastrointestinal hemorrhage: a pilot feasibility study (One-Scope I).

BACKGROUND : Outbreaks of multidrug-resistant bacteria due to contaminated duodenoscopes and infection risks during the COVID-19 pandemic have driven the development of single-use endoscopes. The first single-use gastroscope is now available in Europe. Besides waste disposal and cost issues, the infection risk and performance remain unclear. We aimed to evaluate a single-use gastroscope in patients with signs of upper gastrointestinal bleeding. METHODS : 20 consecutive patients presenting with clinical signs of upper gastrointestinal bleeding between October and November 2022 were included in this case series. The primary aim was technical success, defined as access to the descending duodenum and adequate assessment of the upper gastrointestinal tract for the presence of a bleeding site. RESULTS : The primary aim was achieved in 19/20 patients (95 %). The bleeding site was identified in 18 patients. A therapeutic intervention was performed in six patients (two cap-mounted clips, one standard hemostatic clip, two variceal band ligations, one hemostatic powder, two adrenaline injections); technical and clinical success were achieved in all six patients. Two crossovers to a standard gastroscope occurred. CONCLUSIONS : Use of single-use gastroscopes may be feasible for patients presenting for urgent endoscopic evaluation and treatment of upper gastrointestinal bleeding.

Performance of the VitaPCR rapid molecular test for SARS-CoV-2 screening at hospital admission.

OBJECTIVE: To evaluate the diagnostic accuracy of rapid VitaPCR™ (Credo) assay as screening test in emergency department (ED) patients prior to transfer or medical interventions. METHODS: In this prospective study 6642 oropharyngeal swabs from nonpreselected ED patients were tested for SARS-CoV-2 with (1) extraction-free VitaPCR and (2) extraction-based reference assays (Aptima®, cobas®, Xpert®Xpress). RESULTS: The median TAT of VitaPCR was 47 minutes (IQR: 38-59), while reference assays required 6.2 hours (IQR: 4.4-13.3). VitaPCR's sensitivity, specificity, PPV and NPV was 77.9%, 99.9%, 97.9%, and 98.9% in relation to Hologic Panther TMA; 78.3%, 99.8%, 96.4%, and 98.5% compared to Roche cobas6800 PCR; 71.2%, 99.2%, 94.9%, and 94.3% using Cepheid GeneXpert PCR as reference. CONCLUSION: High-sensitivity testing is needed to limit nosocomial spread and identify asymptomatic COVID-19 patients. However, time advantage of the VitaPCR must be weighed against its significantly lower sensitivity, especially when used in high-risk environments such as hospitals.

One year of COVID-19 pandemic: Health care workers' infection rates and economical burden in medical facilities for oral and maxillofacial surgery.

The aim of this study was to create an overview on the COVID-associated burdens faced by the oral and maxillofacial surgery (OMS) workforce during 1 year of the pandemic. OMS hospitals and private practices nationwide were surveyed regarding health care worker (HCW) screening, infection status, pre-interventional testing, personal protective equipment (PPE), and economic impact. Participants were recruited via the German Society for Oral and Maxillofacial Surgery. A total of 11 hospitals (416 employees) and 55 private practices (744 employees) participated. The HCW infection rate was significantly higher in private practices than in clinics (4.7% vs. 1.4%, p<0.01), although most infections in HCW occurred in private environment (hospitals 88.2%, private practice 66.7%). Pre-interventional testing was performed significantly less for outpatients in private practices than in hospitals (90.7% vs. 36.4%, p<0.01). Polymerase chain reaction (PCR) was used significantly more for inpatients in hospitals than in private practices (100.0% vs. 27.3%, p<0.01). FFP2/3 use rose significantly in hospitals (0% in second quarter vs. 46% in fourth quarter, p<0.05) and private practices (15% in second quarter vs. 38% in fourth quarter, p<0.01). The decrease in procedures (≤50%) was significantly higher in hospitals than in private practices (90.9% vs. 40.0%, p<0.01). Despite higher infection rates in private practices, declining procedures and revenue affected hospitals more. Future COVID-related measures must adjust the infrastructure especially for hospitals to prevent further straining of staff and finances.

Hospitalized patients dying with SARS-CoV-2 infection-An analysis of patient characteristics and management in ICU and general ward of the LEOSS registry.

BACKGROUND: COVID-19 is a severe disease with a high need for intensive care treatment and a high mortality rate in hospitalized patients. The objective of this study was to describe and compare the clinical characteristics and the management of patients dying with SARS-CoV-2 infection in the acute medical and intensive care setting. METHODS: Descriptive analysis of dying patients enrolled in the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS), a non-interventional cohort study, between March 18 and November 18, 2020. Symptoms, comorbidities and management of patients, including palliative care involvement, were compared between general ward and intensive care unit (ICU) by univariate analysis. RESULTS: 580/4310 (13%) SARS-CoV-2 infected patients died. Among 580 patients 67% were treated on ICU and 33% on a general ward. The spectrum of comorbidities and symptoms was broad with more comorbidities (≥ four comorbidities: 52% versus 25%) and a higher age distribution (>65 years: 98% versus 70%) in patients on the general ward. 69% of patients were in an at least complicated phase at diagnosis of the SARS-CoV-2 infection with a higher proportion of patients in a critical phase or dying the day of diagnosis treated on ICU (36% versus 11%). While most patients admitted to ICU came from home (71%), patients treated on the general ward came likewise from home and nursing home (44% respectively) and were more frequently on palliative care before admission (29% versus 7%). A palliative care team was involved in dying patients in 15%. Personal contacts were limited but more often documented in patients treated on ICU (68% versus 47%). CONCLUSION: Patients dying with SARS-CoV-2 infection suffer from high symptom burden and often deteriorate early with a demand for ICU treatment. Therefor a demand for palliative care expertise with early involvement seems to exist.

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584.

Factors associated with an increased risk of SARS-CoV-2 infection in healthcare workers in aerosol-generating disciplines.

BACKGROUND: Healthcare workers (HCWs) are at a high risk of SARS-CoV-2 infection due to exposure to potentially infectious material, especially during aerosol-generating procedures (AGP). We aimed to investigate risk factors for SARS-CoV-2 infection among HCWs in medical disciplines with AGP. METHODS: A nationwide questionnaire-based study in private practices and hospital settings was conducted between 12/16/2020 and 01/24/2021. Data on SARS-CoV-2 infections among HCWs and potential risk factors of infection were investigated. RESULTS: 2070 healthcare facilities with 25113 employees were included in the study. The overall infection rate among HCWs was 4.7%. Multivariate analysis showed that regions with higher incidence rates had a significantly increased risk of infection. Furthermore, hospital setting and HCWs in gastrointestinal endoscopy (GIE) had more than double the risk of infection (OR 2.63; 95% CI 2.50-2.82, p<0.01 and OR 2.35; 95% CI 2.25-2.50, p<0.01). For medical facilities who treated confirmed SARS-CoV-2 cases, there was a tendency towards higher risk of infection (OR 1.39; 95% CI 1.11-1.63, p=0.068). CONCLUSION: Both factors within and outside medical facilities appear to be associated with an increased risk of infection among HCWs. Therefore, GIE and healthcare delivery setting were related to increased infection rates. Regions with higher SARS-CoV-2 incidence rates were also significantly associated with increased risk of infection.

A Simulation-Based Cost-Effectiveness Analysis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Prevention Strategies for Visitors of Healthcare Institutions.

OBJECTIVES: The aim is to quantitatively evaluate different infection prevention strategies in the context of hospital visitor management during pandemics and to provide a decision support system for strategic and operational decisions based on this evaluation. METHODS: A simulation-based cost-effectiveness analysis is applied to the data of a university hospital in Southern Germany and published COVID-19 research. The performance of different hospital visitor management strategies is evaluated by several decision-theoretic methods with varying objective functions. RESULTS: Appropriate visitor restrictions and infection prevention measures can reduce additional infections and costs caused by visitors of healthcare institutions by >90%. The risk of transmission of severe acute respiratory syndrome coronavirus 2 by visitors of terminal care (ie, palliative care) patients can be reduced almost to 0 if appropriate infection prevention measures are implemented. Antigen tests do not seem to be beneficial from both a cost and an effectiveness perspective. CONCLUSIONS: Hospital visitor management is crucial and effectively prevents infections while maintaining cost-effectiveness. For terminal care patients, visitor restrictions can be omitted if appropriate infection prevention measures are taken. Antigen testing plays a subordinate role, except in the case of a pure focus on additional infections caused by visitors of healthcare institutions. We provide decision support to authorities and hospital visitor managers to identify appropriate visitor restriction and infection prevention strategies for specific local conditions, incidence rates, and objectives.

Obesity and Impaired Metabolic Health Increase Risk of COVID-19-Related Mortality in Young and Middle-Aged Adults to the Level Observed in Older People: The LEOSS Registry.

Advanced age, followed by male sex, by far poses the greatest risk for severe COVID-19. An unresolved question is the extent to which modifiable comorbidities increase the risk of COVID-19-related mortality among younger patients, in whom COVID-19-related hospitalization strongly increased in 2021. A total of 3,163 patients with SARS-COV-2 diagnosis in the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort were studied. LEOSS is a European non-interventional multi-center cohort study established in March 2020 to investigate the epidemiology and clinical course of SARS-CoV-2 infection. Data from hospitalized patients and those who received ambulatory care, with a positive SARS-CoV-2 test, were included in the study. An additive effect of obesity, diabetes and hypertension on the risk of mortality was observed, which was particularly strong in young and middle-aged patients. Compared to young and middle-aged (18-55 years) patients without obesity, diabetes and hypertension (non-obese and metabolically healthy; n = 593), young and middle-aged adult patients with all three risk parameters (obese and metabolically unhealthy; n = 31) had a similar adjusted increased risk of mortality [OR 7.42 (95% CI 1.55-27.3)] as older (56-75 years) non-obese and metabolically healthy patients [n = 339; OR 8.21 (95% CI 4.10-18.3)]. Furthermore, increased CRP levels explained part of the elevated risk of COVID-19-related mortality with age, specifically in the absence of obesity and impaired metabolic health. In conclusion, the modifiable risk factors obesity, diabetes and hypertension increase the risk of COVID-19-related mortality in young and middle-aged patients to the level of risk observed in advanced age.

Artificial Intelligence-Based Detection of Pneumonia in Chest Radiographs.

Artificial intelligence is gaining increasing relevance in the field of radiology. This study retrospectively evaluates how a commercially available deep learning algorithm can detect pneumonia in chest radiographs (CR) in emergency departments. The chest radiographs of 948 patients with dyspnea between 3 February and 8 May 2020, as well as 15 October and 15 December 2020, were used. A deep learning algorithm was used to identify opacifications associated with pneumonia, and the performance was evaluated by using ROC analysis, sensitivity, specificity, PPV and NPV. Two radiologists assessed all enrolled images for pulmonal infection patterns as the reference standard. If consolidations or opacifications were present, the radiologists classified the pulmonal findings regarding a possible COVID-19 infection because of the ongoing pandemic. The AUROC value of the deep learning algorithm reached 0.923 when detecting pneumonia in chest radiographs with a sensitivity of 95.4%, specificity of 66.0%, PPV of 80.2% and NPV of 90.8%. The detection of COVID-19 pneumonia in CR by radiologists was achieved with a sensitivity of 50.6% and a specificity of 73%. The deep learning algorithm proved to be an excellent tool for detecting pneumonia in chest radiographs. Thus, the assessment of suspicious chest radiographs can be purposefully supported, shortening the turnaround time for reporting relevant findings and aiding early triage.

One Year of the COVID-19 Pandemic in Dental Medical Facilities in Germany: A Questionnaire-Based Analysis.

(1) Background: The COVID-19 pandemic forced healthcare workers to adapt to challenges in both patient care and self-protection. Dental practitioners were confronted with a potentially high possibility of infection transmission due to aerosol-generating procedures. This study aims to present data on healthcare worker (HCW) screening, infection status of HCWs, pre-interventional testing, the use of personal protective equipment (PPE) and the economic impact of the pandemic in dental facilities. (2) Methods: Dental facilities were surveyed nationwide using an online questionnaire. The acquisition of participants took place in cooperation with the German Society for Dentistry, Oral and Maxillofacial Medicine. (3) Results: A total of 1094 private practices participated. Of these, 39.1% treated fewer than 600 patients per quarter and 59.9% treated over 600 patients per quarter. Pre-interventional testing was rarely performed in either small (6.6%) or large practices (6.0%). Large practices had a significantly higher incidence of at least one SARS-CoV-2-positive HCW than small practices (26.2% vs.14.4%, p < 0.01). The main source of infection in small practices was the private environment, and this was even more significant in large practices (81.8% vs. 89.7%, p < 0.01). The procedure count either remained stable (34.0% of small practices vs. 46.2% of large practices) or decreased by up to 50% (52.6% of small practices vs. 44.4% of large practices). Revenue remained stable (24.8% of small practices vs. 34.2% of large practices) or decreased by up to 50% (64.5% of small practices vs. 55.3% of large practices, p = 0.03). Overall, employee numbers remained stable (75.5% of small practices vs. 76.8% of large practices). A vaccination readiness of 60-100% was shown in 60.5% (n = 405) of large practices and 59.9% (n = 251) of small practices. (4) Conclusion: Pre-interventional testing in dental practices should be increased further. Economic challenges affected small practices as well as large practices. Overall, a steady employee count could be maintained. Vaccination readiness is high in dental practices, although with some room for improvement.

Antibody Response to SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Disease: Results of a Single-Center Cohort Study in a Tertiary Hospital in Germany.

BACKGROUND: COVID-19 is a viral disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), first described in 2019, with a significant impact on everyday life since then. In December 2020, the first vaccine against COVID-19 from BioNTech/Pfizer was approved for the first time. However, little is known about the immune response to vaccination in patients with inflammatory bowel disease (IBD) and immunomodulators or biologics. The aim of our study was to investigate antibody response to SARS-CoV-2 vaccination in patients with IBD receiving immunomodulators or biologics compared to healthy controls. METHODS: This was a single-center study with a retrospective observational design. Seventy-two patients with ulcerative colitis or Crohn's disease were included. Matching data from 72 healthy employees of our hospital were used as the control group. Data were matched by propensity score to patients with IBD. Blood samples were taken from both groups for antibody response, and both groups received an accompanying questionnaire. RESULTS: Sixty-five (90.3%) patients of the IBD group reported taking immunomodulatory therapy. The mean antibody level for all IBD patients was 1,257.1 U/mL (standard deviation [SD] 1,109.626) in males and 1,500.1 U/mL (SD 1142.760) in female IBD patients after full vaccination. Compared to the healthy group, reduced antibody response could be detected (IBD group 1,383.76 U/mL SD 1,125.617; control group 1,885.65 U/mL SD 727.572, p < 0.05). In this group, blood samples were taken with an average of 61.9 days after the first vaccination. There was no vaccination failure in the IBD group after 2 vaccinations. After the first vaccination, side effects, including muscle pain, pain at the injection site, and fatigue, were reported more often in IBD patients than in the control group (total symptoms IBD group 58.3%, control group 34.5%, p < 0.007). The opposite occurred after the second vaccination when side effects were higher in the control group (total symptoms IBD group 55.4%, control group 76%, p = 0.077). There was a trend to a reduced immune response in elderly patients. Disease duration and concomitant immunomodulatory therapy (TNF-alpha blockers, interleukin inhibitors, integrin inhibitors, methotrexate, or azathioprine) had no impact on the immune response. However, longer time to last medication given and time passed to vaccination in patients with IBD seems to have a positive impact on antibody levels. CONCLUSION: Overall, we could show a high antibody response to vaccination with COVID-19 in all patients with IBD after 2 vaccinations. Vaccination was well tolerated, and no other adverse events were detected. Concomitant immunomodulatory therapy (TNF-alpha blockers, interleukin inhibitors, integrin inhibitors, methotrexate, or azathioprine) had no impact on seroconversion. Further evaluation of antibody titers over time is mandatory to detect early the need for re-vaccination in these patients.

Comparison of the Development of SARS-Coronavirus-2-Specific Cellular Immunity, and Central Memory CD4+ T-Cell Responses Following Infection versus Vaccination.

Memory T-cell responses following infection with coronaviruses are reportedly long-lived and provide long-term protection against severe disease. Whether vaccination induces similar long-lived responses is not yet clear since, to date, there are limited data comparing memory CD4+ T-cell responses induced after SARS-CoV-2 infection versus following vaccination with BioNTech/Pfizer BNT162b2. We compared T-cell immune responses over time after infection or vaccination using ELISpot, and memory CD4+ T-cell responses three months after infection/vaccination using activation-induced marker flow cytometric assays. Levels of cytokine-producing T-cells were remarkably stable between three and twelve months after infection, and were comparable to IFNγ+ and IFNγ+IL-2+ T-cell responses but lower than IL-2+ T-cell responses at three months after vaccination. Consistent with this finding, vaccination and infection elicited comparable levels of SARS-CoV-2 specific CD4+ T-cells after three months in addition to comparable proportions of specific central memory CD4+ T-cells. By contrast, the proportions of specific effector memory CD4+ T-cells were significantly lower, whereas specific effector CD4+ T-cells were higher after infection than after vaccination. Our results suggest that T-cell responses-as measured by cytokine expression-and the frequencies of SARS-CoV-2-specific central memory CD4+T-cells-indicative of the formation of the long-lived memory T-cell compartment-are comparably induced after infection and vaccination.

Impaired Dendritic Cell Homing in COVID-19.

The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies aiming to depict this dysregulation have mostly investigated the peripheral cell count as well as the functionality of immune cells. We investigated the impact of SARS-CoV-2 on antigen-presenting cells using multiplexed immunofluorescence. Similar to MERS-CoV and SARS-CoV, SARS-CoV-2 appears to be impairing the maturation of dendritic cells (DCs). DC maturation involves a switch in surface antigen expression, which enables the cells' homing to lymph nodes and the subsequent activation of T-cells. As quantitative descriptions of the local inflammatory infiltrate are still scarce, we compared the cell population of professional antigen-presenting cells (APC) in the lungs of COVID-19 autopsy cases in different stages of DAD. We found an increased count of myeloid dendritic cells (mDCs) in later stages. Interestingly, mDCs also showed no significant upregulation of maturation markers in DAD-specimens with high viral load. Accumulation of immature mDCs, which are unable to home to lymph nodes, ultimately results in an inadequate T-cell response.

[Impact of Covid 19 on endoscopy in Germany]. / Ein Jahr Covid-19: Testung, Verwendung von Schutzausrüstung und Auswirkungen auf die Gastrointestinale Endoskopie in Deutschland.

BACKGROUND: Practices and hospitals are facing great challenges in coping with the COVID-19-pandemic. So far, data on the impact of the pandemic on gastroenterological facilities are lacking, especially on a temporal course. A database is lacking, especially for the outpatient care sector. University Hospital of Augsburg was commissioned to generate data on this as a part of the collaborative project B-FAST of the Network of University Medicine (NUM). METHODS: Gastroenterological institutions nationwide were surveyed by an online questionnaire. Recruitment was carried out via the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the Professional Association of Gastroenterologists in Private Practice (bng). This manuscript provides an overview of data on the use of protective equipment, pre-interventional testing of patients, staff screening and economic impact over the course of the pandemic. RESULTS: 429 facilities answered the questionnaire. Practices tested their patients pre-interventionally significantly less often than clinics (7.8% vs. 82.6%). In clinics, inpatients (93.1%) were tested significantly more often than outpatients (72.2%). The use of personal protective equipment (PPE) increased significantly during the pandemic. It was shown that over 70% of facilities screened their staff for SARS-CoV-2 without cause. Clinics cancelled elective procedures significantly more often than practices in quarter 4/2020. Procedures and turnover decreased in 2020 compared to the previous year. However, fewer facilities were affected by a loss of revenue than expected in previous studies. CONCLUSION: Our data demonstrate the variable implementation of pre-interventional SARS-CoV-2 testing in outpatient and inpatient care. The use of adequate PPE and staff screening increased during the pandemic.

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

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

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

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

Evaluation of the ESGE recommendations for COVID-19 pre-endoscopy risk-stratification in a high-volume center in Germany.

Background and study aims The European Society of Gastrointestinal Endoscopy (ESGE) has defined COVID-19 infection prevention and control strategies within the endoscopy unit. These include pre-endoscopic questionnaire-based risk-stratification as well as pre-procedure viral testing. Real-life data on the effectiveness of these measures are presented here. Patients and methods Data from the outpatient endoscopic unit of the University Hospital Augsburg between July 1, 2020 and December 31, 2020 including the second pandemic wave were reviewed retrospectively. All patients were assessed with a pre-endoscopic risk-stratification questionnaire as well as viral testing using an antigen point-of-care test (Ag-POCT) in conjunction with a standard polymerase chain reaction (PCR) test. Highly elective procedures were postponed. The theoretically expected number of SARS-CoV-2-positive patients was simulated and compared with the actual number. In addition, endoscopy staff was evaluated with a rapid antibody test to determine the number of infections among the personnel. Results In total, 1029 procedures, 591 questionnaires, 591 Ag-POCTs, and 529 standard PCR tests were performed in 591 patients. 247 procedures in 142 patients were postponed. One Ag-POCT was positive but with a negative PCR test, while one PCR test was positive but with a negative Ag-POCT. This was lower than the theoretically expected number of COVID-19-positive patients (n = 15). One of 43 employees (2.3 %) in the outpatient endoscopy unit was seropositive. Conclusions Pre-endoscopic risk management including questionnaire-based risk stratification and viral testing seems to be an effective tool in combination with personal protective equipment for SARS-CoV-2 infection prevention and control within the endoscopy unit even in a high-prevalence setting.

Performance of antigen testing for diagnosis of COVID-19: a direct comparison of a lateral flow device to nucleic acid amplification based tests.

OBJECTIVES: The gold standard for diagnosing an infection with SARS-CoV-2 is detection of viral RNA by nucleic acid amplification techniques. Test capacities, however, are limited. Therefore, numerous easy-to-use rapid antigen tests based on lateral flow technology have been developed. Manufacturer-reported performance data seem convincing, but real-world data are missing. METHODS: We retrospectively analysed all prospectively collected antigen tests results performed between 23.06.2020 and 26.11.2020, generated by non-laboratory personnel at the point-of-care from oro- or nasopharyngeal swab samples at the University Hospital Augsburg and compared them to concomitantly (within 24 h.) generated results from molecular tests. RESULTS: For a total of 3630 antigen tests, 3110 NAAT results were available. Overall, sensitivity, specificity, NPV and PPV of antigen testing were 59.4%, 99.0%, 98.7% and 64.8%, respectively. Sensitivity and PPV were lower in asymptomatic patients (47.6% and 44.4%, respectively) and only slightly higher in patients with clinical symptoms (66.7% and 85.0%, respectively). Some samples with very low Ct-values (minimum Ct 13) were not detected by antigen testing. 31 false positive results occurred. ROC curve analysis showed that reducing the COI cut-off from 1, as suggested by the manufacturer, to 0.9 is optimal, albeit with an AUC of only 0.66. CONCLUSION: In real life, performance of lateral-flow-based antigen tests are well below the manufacturer's specifications, irrespective of patient's symptoms. Their use for detection of individual patients infected with SARS-CoV2 should be discouraged. This does not preclude their usefulness in large-scale screening programs to reduce transmission events on a population-wide scale.

One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms.

After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 and investigated correlations of immunity with persistent symptoms and immune longevity. Persistent complications, including headache, concentration difficulties and loss of smell/taste, were reported by 51 of 83 (61%) participants and decreased over time to 28% one year after COVID-19. Specific IgA and IgG antibodies were detectable in 78% and 66% of participants, respectively, at a 12-month follow-up. Median antibody levels decreased by approximately 50% within the first 6 months but remained stable up to 12 months. Neutralizing antibodies could be found in 50% of participants; specific INFgamma-producing T-cells were present in two thirds one year after COVID-19. Activation-induced marker assays identified specific T-helper cells and central memory T-cells in 80% of participants at a 12-month follow-up. In correlative analyses, older age and a longer duration of the acute phase of COVID-19 were associated with higher humoral and T-cell responses. A weak correlation between long-term loss of taste/smell and low IgA levels was found at early time points. These data indicate a long-lasting immunological memory against SARS-CoV-2 after mild COVID-19.