Pre-existing sleep problems as a predictor of post-acute sequelae of COVID-19.

Several months after COVID-19 many individuals still report persisting symptoms, the so-called 'post-COVID-19 syndrome'. An immunological dysfunction is one of the main pathophysiological hypotheses. As sleep is central to the functioning of the immune system, we investigated whether self-reported pre-existing sleep disturbance might be an independent risk factor for the development of post-COVID-19 syndrome. A total of 11,710 participants of a cross-sectional survey (all tested positive for severe acute respiratory syndrome coronavirus-2) were classified into probable post-COVID-19 syndrome, an intermediate group, and unaffected participants at an average of 8.5 months after infection. The case definition was based on newly occurring symptoms of at least moderate severity and ≥20% reduction in health status and/or working capacity. Unadjusted and adjusted odds ratios were calculated to investigate the association between pre-existing sleep disturbances and subsequent development of post-COVID-19 syndrome while controlling for a variety of demographic, lifestyle, and health factors. Pre-existing sleep disturbances were found to be an independent predictor of subsequent probable post-COVID-19 syndrome (adjusted odds ratio 2.7, 95% confidence interval 2.27-3.24). Sleep disturbances as part of the post-COVID-19 syndrome were reported by more than half of the participants and appeared to be a new symptom and to occur independent of a mood disorder in most cases. Recognition of disturbed sleep as an important risk factor for post-COVID-19 syndrome should promote improved clinical management of sleep disorders in the context of COVID-19. Further, it may stimulate further research on the effect of improving sleep on the prognosis of COVID-19 long-term sequelae and other post-viral conditions.

Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients.

Background: Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course. Methods: This study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). 1H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes. Results: Here, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients. Conclusion: The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.

Patterns of acute ischemic stroke and intracranial hemorrhage in patients with COVID-19 : Results of a retrospective multicenter neuroimaging-based study from three central European countries.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infection which can affect the central nervous system. In this study, we sought to investigate associations between neuroimaging findings with clinical, demographic, blood and cerebrospinal fluid (CSF) parameters, pre-existing conditions and the severity of acute COVID-19. MATERIALS AND METHODS: Retrospective multicenter data retrieval from 10 university medical centers in Germany, Switzerland and Austria between February 2020 and September 2021. We included patients with COVID-19, acute neurological symptoms and cranial imaging. We collected demographics, neurological symptoms, COVID-19 severity, results of cranial imaging, blood and CSF parameters during the hospital stay. RESULTS: 442 patients could be included. COVID-19 severity was mild in 124 (28.1%) patients (moderate n = 134/30.3%, severe n = 43/9.7%, critical n = 141/31.9%). 220 patients (49.8%) presented with respiratory symptoms, 167 (37.8%) presented with neurological symptoms first. Acute ischemic stroke (AIS) was detected in 70 (15.8%), intracranial hemorrhage (IH) in 48 (10.9%) patients. Typical risk factors were associated with AIS; extracorporeal membrane oxygenation therapy and invasive ventilation with IH. No association was found between the severity of COVID-19 or blood/CSF parameters and the occurrence of AIS or IH. DISCUSSION: AIS was the most common finding on cranial imaging. IH was more prevalent than expected but a less common finding than AIS. Patients with IH had a distinct clinical profile compared to patients with AIS. There was no association between AIS or IH and the severity of COVID-19. A considerable proportion of patients presented with neurological symptoms first. Laboratory parameters have limited value as a screening tool.

Machine learning models for predicting severe COVID-19 outcomes in hospitals.

The aim of this observational retrospective study is to improve early risk stratification of hospitalized Covid-19 patients by predicting in-hospital mortality, transfer to intensive care unit (ICU) and mechanical ventilation from electronic health record data of the first 24 h after admission. Our machine learning model predicts in-hospital mortality (AUC = 0.918), transfer to ICU (AUC = 0.821) and the need for mechanical ventilation (AUC = 0.654) from a few laboratory data of the first 24 h after admission. Models based on dichotomous features indicating whether a laboratory value exceeds or falls below a threshold perform nearly as good as models based on numerical features. We devise completely data-driven and interpretable machine-learning models for the prediction of in-hospital mortality, transfer to ICU and mechanical ventilation for hospitalized Covid-19 patients within 24 h after admission. Numerical values of. CRP and blood sugar and dichotomous indicators for increased partial thromboplastin time (PTT) and glutamic oxaloacetic transaminase (GOT) are amongst the best predictors.

Association of BMI with general health, working capacity recovered, and post-acute sequelae of COVID-19.

OBJECTIVE: The aim of this study was to determine the risk of post-acute sequelae of COVID-19 associated with the continuous spectrum of BMI. METHODS: Epidemiology of Long COVID (EPILOC) is a population-based study conducted in Baden-Württemberg (Germany), including subjects aged 18 to 65 years who tested positive for SARS-CoV-2 between October 2020 and April 2021. Eligible subjects answered a standardized questionnaire, including sociodemographic characteristics, lifestyle factors, and the presence of specific symptoms. Participants assessed their current general health recovery and working capacity compared with the pre-infection situation and provided their body height and weight. Generalized additive models were used to assess the association of BMI with general health recovered, working capacity recovered, and prevalence of fatigue, cognitive impairment, and chest symptoms. RESULTS: The analyses included 11,296 individuals (41% male), with a mean age of 44.0 (SD 13.7) years. Best general health recovery was observed at BMI of 22.1 (95% CI: 21.0-27.0) kg/m2 in men and BMI of 21.6 (95% CI: 20.3-23.1) kg/m2 in women. In addition, we found that increasing BMI was consistently associated with post-COVID fatigue, neurocognitive impairment, and chest symptoms. CONCLUSIONS: High BMI contributes to impaired recovery after SARS-CoV-2 infection; however, a low BMI is associated with impaired recovery as well.

Antibody binding and ACE2 binding inhibition is significantly reduced for both the BA1 and BA2 omicron variants.

BACKGROUND: The rapid emergence of the omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the WHO. Subsequently, omicron evolved into distinct sublineages (e.g. BA1 and BA2), which currently represent the majority of global infections. Initial studies of the neutralizing response towards BA1 in convalescent and vaccinated individuals showed a substantial reduction. METHODS: We assessed antibody (IgG) binding, ACE2 (Angiotensin-Converting Enzyme 2) binding inhibition, and IgG binding dynamics for the omicron BA1 and BA2 variants compared to a panel of VOC/VOIs, in a large cohort (n = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals. RESULTS: While omicron was capable efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to WT. Whereas BA1 exhibited less IgG binding compared to BA2, BA2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to omicron only improved after administration of a third dose. CONCLUSION: omicron BA1 and BA2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind omicron. The extent of the mutations within both variants prevent a strong inhibitory binding response. As a result, both omicron variants are able to evade control by pre-existing antibodies.

Machine learning models for predicting severe COVID-19 outcomes in hospitals

The aim of this observational retrospective study is to improve early risk stratification of hospitalized Covid-19 patients by predicting in-hospital mortality, transfer to intensive care unit (ICU) and mechanical ventilation from electronic health record data of the first 24 hours after admission. Our machine learning model predicts in-hospital mortality (AUC = 0.918), transfer to ICU (AUC = 0.821) and the need for mechanical ventilation (AUC = 0.654) from a few laboratory data of the first 24 hours after admission. Models based on dichotomous features indicating whether a laboratory value exceeds or falls below a threshold perform nearly as good as models based on numerical features. We devise completely data-driven and interpretable machine-learning models for the prediction of in-hospital mortality, transfer to ICU and mechanical ventilation for hospitalized Covid-19 patients within 24 hours after admission. Numerical values of. CRP and blood sugar and dichotomous indicators for increased partial thromboplastin time (PTT) and glutamic oxaloacetic transaminase (GOT) are amongst the best predictors. Graphical Image 1

Increased soluble HLA in COVID-19 present a disease-related, diverse immunopeptidome associated with T cell immunity.

HLA-presented antigenic peptides are central components of T cell-based immunity in infectious disease. Beside HLA molecules on cell surfaces, soluble HLA molecules (sHLA) are released in the blood suggested to impact cellular immune responses. We demonstrated that sHLA levels were significantly increased in COVID-19 patients and convalescent individuals compared to a control cohort and positively correlated with SARS-CoV-2-directed cellular immunity. Of note, patients with severe courses of COVID-19 showed reduced sHLA levels. Mass spectrometry-based characterization of sHLA-bound antigenic peptides, the so-called soluble immunopeptidome, revealed a COVID-19-associated increased diversity of HLA-presented peptides and identified a naturally presented SARS-CoV-2-derived peptide from the viral nucleoprotein in the plasma of COVID-19 patients. Of interest, sHLA serum levels directly correlated with the diversity of the soluble immunopeptidome. Together, these findings suggest an inflammation-driven release of sHLA in COVID-19, directly influencing the diversity of the soluble immunopeptidome with implications for SARS-CoV-2-directed T cell-based immunity and disease outcome.

External Validation of COVID-19 Risk Scores during Three Waves of Pandemic in a German Cohort-A Retrospective Study.

Several risk scores were developed during the COVID-19 pandemic to identify patients at risk for critical illness as a basic step to personalizing medicine even in pandemic circumstances. However, the generalizability of these scores with regard to different populations, clinical settings, healthcare systems, and new epidemiological circumstances is unknown. The aim of our study was to compare the predictive validity of qSOFA, CRB65, NEWS, COVID-GRAM, and 4C-Mortality score. In a monocentric retrospective cohort, consecutively hospitalized adults with COVID-19 from February 2020 to June 2021 were included; risk scores at admission were calculated. The area under the receiver operating characteristic curve and the area under the precision-recall curve were compared using DeLong's method and a bootstrapping approach. A total of 347 patients were included; 23.6% were admitted to the ICU, and 9.2% died in a hospital. NEWS and 4C-Score performed best for the outcomes ICU admission and in-hospital mortality. The easy-to-use bedside score NEWS has proven to identify patients at risk for critical illness, whereas the more complex COVID-19-specific scores 4C and COVID-GRAM were not superior. Decreasing mortality and ICU-admission rates affected the discriminatory ability of all scores. A further evaluation of risk assessment is needed in view of new and rapidly changing epidemiological evolution.

Post-acute sequelae of covid-19 six to 12 months after infection: population based study.

OBJECTIVES: To describe symptoms and symptom clusters of post-covid syndrome six to 12 months after acute infection, describe risk factors, and examine the association of symptom clusters with general health and working capacity. DESIGN: Population based, cross sectional study SETTING: Adults aged 18-65 years with confirmed SARS-CoV-2 infection between October 2020 and March 2021 notified to health authorities in four geographically defined regions in southern Germany. PARTICIPANTS: 50 457 patients were invited to participate in the study, of whom 12 053 (24%) responded and 11 710 (58.8% (n=6881) female; mean age 44.1 years; 3.6% (412/11 602) previously admitted with covid-19; mean follow-up time 8.5 months) could be included in the analyses. MAIN OUTCOME MEASURES: Symptom frequencies (six to 12 months after versus before acute infection), symptom severity and clustering, risk factors, and associations with general health recovery and working capacity. RESULTS: The symptom clusters fatigue (37.2% (4213/11 312), 95% confidence interval 36.4% to 38.1%) and neurocognitive impairment (31.3% (3561/11 361), 30.5% to 32.2%) contributed most to reduced health recovery and working capacity, but chest symptoms, anxiety/depression, headache/dizziness, and pain syndromes were also prevalent and relevant for working capacity, with some differences according to sex and age. Considering new symptoms with at least moderate impairment of daily life and ≤80% recovered general health or working capacity, the overall estimate for post-covid syndrome was 28.5% (3289/11 536, 27.7% to 29.3%) among participants or at least 6.5% (3289/50 457) in the infected adult population (assuming that all non-responders had completely recovered). The true value is likely to be between these estimates. CONCLUSIONS: Despite the limitation of a low response rate and possible selection and recall biases, this study suggests a considerable burden of self-reported post-acute symptom clusters and possible sequelae, notably fatigue and neurocognitive impairment, six to 12 months after acute SARS-CoV-2 infection, even among young and middle aged adults after mild infection, with a substantial impact on general health and working capacity. TRIAL REGISTRATION: German registry of clinical studies DRKS 00027012.

Preexisting comorbidities shape the immune response associated with severe COVID-19.

BACKGROUND: Comorbidities are risk factors for development of severe coronavirus disease 2019 (COVID-19). However, the extent to which an underlying comorbidity influences the immune response to severe acute respiratory syndrome coronavirus 2 remains unknown. OBJECTIVE: Our aim was to investigate the complex interrelations of comorbidities, the immune response, and patient outcome in COVID-19. METHODS: We used high-throughput, high-dimensional, single-cell mapping of peripheral blood leukocytes and algorithm-guided analysis. RESULTS: We discovered characteristic immune signatures associated not only with severe COVID-19 but also with the underlying medical condition. Different factors of the metabolic syndrome (obesity, hypertension, and diabetes) affected distinct immune populations, thereby additively increasing the immunodysregulatory effect when present in a single patient. Patients with disorders affecting the lung or heart, together with factors of metabolic syndrome, were clustered together, whereas immune disorder and chronic kidney disease displayed a distinct immune profile in COVID-19. In particular, severe acute respiratory syndrome coronavirus 2-infected patients with preexisting chronic kidney disease were characterized by the highest number of altered immune signatures of both lymphoid and myeloid immune branches. This overall major immune dysregulation could be the underlying mechanism for the estimated odds ratio of 16.3 for development of severe COVID-19 in this burdened cohort. CONCLUSION: The combinatorial systematic analysis of the immune signatures, comorbidities, and outcomes of patients with COVID-19 has provided the mechanistic immunologic underpinnings of comorbidity-driven patient risk and uncovered comorbidity-driven immune signatures.

Host genetic loci LZTFL1 and CCL2 associated with SARS-CoV-2 infection and severity of COVID-19.

OBJECTIVES: Host genetic factors contribute to the variable severity of COVID-19. We examined genetic variants from genome-wide association studies and candidate gene association studies in a cohort of patients with COVID-19 and investigated the role of early SARS-CoV-2 strains in COVID-19 severity. METHODS: This case-control study included 123 COVID-19 cases (hospitalized or ambulatory) and healthy controls from the state of Baden-Wuerttemberg, Germany. We genotyped 30 single nucleotide polymorphisms, using a custom-designed panel. Cases were also compared with the 1000 genomes project. Polygenic risk scores were constructed. SARS-CoV-2 genomes from 26 patients with COVID-19 were sequenced and compared between ambulatory and hospitalized cases, and phylogeny was reconstructed. RESULTS: Eight variants reached nominal significance and two were significantly associated with at least one of the phenotypes "susceptibility to infection", "hospitalization", or "severity": rs73064425 in LZTFL1 (hospitalization and severity, P <0.001) and rs1024611 near CCL2 (susceptibility, including 1000 genomes project, P = 0.001). The polygenic risk score could predict hospitalization. Most (23/26, 89%) of the SARS-CoV-2 genomes were classified as B.1 lineage. No associations of SARS-CoV-2 mutations or lineages with severity were observed. CONCLUSION: These host genetic markers provide insights into pathogenesis and enable risk classification. Variants which reached nominal significance should be included in larger studies.

COVID-19 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants.

As global vaccination campaigns against SARS-CoV-2 proceed, there is particular interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. As SARS-CoV-2 variants of concern (VOCs) are known to affect binding to the ACE2 receptor and by extension neutralizing activity, we developed a bead-based multiplex ACE2-RBD inhibition assay (RBDCoV-ACE2) as a highly scalable, time-, cost-, and material-saving alternative to infectious live-virus neutralization tests. By mimicking the interaction between ACE2 and the RBD, this serological multiplex assay allows the simultaneous analysis of ACE2 binding inhibition to the RBDs of all SARS-CoV-2 VOCs and variants of interest (VOIs) in a single well. Following validation against a classical virus neutralization test and comparison of performance against a commercially available assay, we analyzed 266 serum samples from 168 COVID-19 patients of varying severity. ACE2 binding inhibition was reduced for ten out of eleven variants examined compared to wild-type, especially for those displaying the E484K mutation such as VOCs beta and gamma. ACE2 binding inhibition, while highly individualistic, positively correlated with IgG levels. ACE2 binding inhibition also correlated with disease severity up to WHO grade 7, after which it reduced.

Infection control of COVID-19 in pediatric tertiary care hospitals: challenges and implications for future pandemics.

BACKGROUND: More than 2 years into the COVID-19 pandemic, SARS-CoV-2 still impacts children's health and the management of pediatric hospitals. However, it is unclear which hygiene and infection control measures are effective and useful for pediatric hospitals. Here, we report infection control measures implemented at a tertiary care children's hospital. We evaluated frequency of SARS-CoV-2 detection in admitted patients, in-hospital transmission and infection related findings. Furthermore, we aimed to capture perspectives of health-care workers and caregivers on effectiveness and burden of infection control measures. Knowledge gained can inform management of the ongoing and future pandemics. METHODS: We designed a retrospective observational study and survey at a pediatric tertiary care referral center. Local infection control measures and respective guidelines regarding COVID-19 were reviewed. Three thousand seven hundred sixteen children under 18 years were tested for SARS-CoV-2 at the University Children's Hospital Tuebingen and data on SARS-CoV-2 transmission were retrieved from internal records. Two surveys were conducted among 219 staff members and 229 caregivers. RESULTS: Local infection control measures comprised the formation of a task force, triage, protective hygiene measures and an adaptable SARS-CoV-2 test strategy. Between January 2020 and March 2021, SARS-CoV-2 infection was detected in 37 children presenting to our hospital, 21 of these were admitted. One hospital-acquired infection occurred. About 90% of health-care staff perceived the majority of measures as effective and appropriate. However, visitor restrictions and cancellation of scheduled treatments were perceived least effective by hospital staff and as a particular burden for patients and their caregivers. Visits at the pediatric emergency department significantly decreased during the pandemic. We drafted a pandemic action plan by ranking infection control measures according to local transmission stages. CONCLUSIONS: SARS-CoV-2 infection control measures implemented in our tertiary care children's hospital were evaluated by health-care workers as mostly effective and appropriate. In particular, good communication, transparency of decision-making as well as universal masking and infection screening were assessed as successful measures of infection control management. Visitor restrictions and cancellation of routine appointments, in contrast, were perceived as a particular burden on patient care and should be avoided. An established pandemic action plan may guide children's hospitals in the future.

Analysis of the effects of the first and second/third waves of the COVID-19 pandemic on an Interdisciplinary Endoscopy Unit in a German 'hotspot' area: a single-center experience.

Background: Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a pandemic threat to global health. We are now in the fourth wave of this pandemic. As the pandemic developed, the requirements and therapeutic endoscopic procedures for SARS-CoV-2-positive patients underwent changes. Methods: Analysis of implications for an endoscopy unit during the first and second/third waves of the COVID-19 pandemic with a focus on COVID-19-related process changing. Addressed are number of SARS-CoV-2-positive patients and endoscopic examinations performed in patients who tested positive for SARS-CoV-2 during the various waves, adherence to scheduled examinations, rotation of staff to COVID-dedicated structures and, finally, impact of vaccination on infection rate among endoscopic staff. Results: During the first wave, 10 SARS-CoV-2-positive in-house patients underwent a total of 22 gastrointestinal (GI) endoscopic procedures. During the second and third waves, 59 GI endoscopies were performed in 38 patients. While in the first wave, GI bleeding was the main indication for endoscopy (82%), in the second and third waves the main indication for endoscopy was endoscopic insertion of deep feeding tubes (78%; p < 0.001). During the first wave, 5 (17%) of 29 Interdisciplinary Endoscopy Unit (IEU) staff members were moved to designated COVID wards, which was not necessary during the following waves. Lack of protective clothing was critical during the first wave, but not in the later waves. Screening tests for patients and staff were widely available after the first wave, and IEU staff was vaccinated during the second wave. Conclusion: Strategies to ensure safe endoscopies with respect to preventing transmission of SARS-CoV-2 from patients to staff were effective. Organizational adjustments allowed the routine program to continue unaffected. Indications for GI endoscopies changed over time: during the first wave, GI endoscopies were performed for life-threatening indications, whereas later supportive procedures were the main indication.

Upregulation of cAMP prevents antibody-mediated thrombus formation in COVID-19.

Thromboembolic events are frequently reported in patients infected with the SARS-CoV-2 virus. The exact mechanisms of COVID-19-associated hypercoagulopathy, however, remain elusive. Recently, we observed that platelets (PLTs) from patients with severe COVID-19 infection express high levels of procoagulant markers, which were found to be associated with increased risk for thrombosis. In the current study, we investigated the time course as well as the mechanisms leading to procoagulant PLTs in COVID-19. Our study demonstrates the presence of PLT-reactive IgG antibodies that induce marked changes in PLTs in terms of increased inner-mitochondrial transmembrane potential (Δψ) depolarization, phosphatidylserine (PS) externalization, and P-selectin expression. The IgG-induced procoagulant PLTs and increased thrombus formation were mediated by ligation of PLT Fc-γ RIIA (FcγRIIA). In addition, contents of calcium and cyclic-adenosine-monophosphate (cAMP) in PLTs were identified to play a central role in antibody-induced procoagulant PLT formation. Most importantly, antibody-induced procoagulant events, as well as increased thrombus formation in severe COVID-19, were inhibited by Iloprost, a clinically approved therapeutic agent that increases the intracellular cAMP levels in PLTs. Our data indicate that upregulation of cAMP could be a potential therapeutic target to prevent antibody-mediated coagulopathy in COVID-19 disease.

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.

Specific Risk Factors for Fatal Outcome in Critically Ill COVID-19 Patients: Results from a European Multicenter Study.

(1) Background: The aim of our study was to identify specific risk factors for fatal outcome in critically ill COVID-19 patients. (2) Methods: Our data set consisted of 840 patients enclosed in the LEOSS registry. Using lasso regression for variable selection, a multifactorial logistic regression model was fitted to the response variable survival. Specific risk factors and their odds ratios were derived. A nomogram was developed as a graphical representation of the model. (3) Results: 14 variables were identified as independent factors contributing to the risk of death for critically ill COVID-19 patients: age (OR 1.08, CI 1.06-1.10), cardiovascular disease (OR 1.64, CI 1.06-2.55), pulmonary disease (OR 1.87, CI 1.16-3.03), baseline Statin treatment (0.54, CI 0.33-0.87), oxygen saturation (unit = 1%, OR 0.94, CI 0.92-0.96), leukocytes (unit 1000/µL, OR 1.04, CI 1.01-1.07), lymphocytes (unit 100/µL, OR 0.96, CI 0.94-0.99), platelets (unit 100,000/µL, OR 0.70, CI 0.62-0.80), procalcitonin (unit ng/mL, OR 1.11, CI 1.05-1.18), kidney failure (OR 1.68, CI 1.05-2.70), congestive heart failure (OR 2.62, CI 1.11-6.21), severe liver failure (OR 4.93, CI 1.94-12.52), and a quick SOFA score of 3 (OR 1.78, CI 1.14-2.78). The nomogram graphically displays the importance of these 14 factors for mortality. (4) Conclusions: There are risk factors that are specific to the subpopulation of critically ill COVID-19 patients.

Can follow up lung ultrasound in Coronavirus Disease-19 patients indicate clinical outcome?

PURPOSE: To evaluate whether there is a change in findings of coronavirus disease 2019 patients in follow up lung ultrasound and to determine whether these findings can predict the development of severe disease. MATERIALS AND METHODS: In this prospective monocentric study COVID-19 patients had standardized lung ultrasound (12 area evaluation) at day 1, 3 and 5. The primary end point was detection of pathologies and their change over time. The secondary end point was relationship between change in sonographic results and clinical outcome. Clinical outcome was assessed on development of severe disease defined as need for intensive care unit. RESULTS: Data of 30 patients were analyzed, 26 patients with follow-up lung ultrasound. All of them showed lung pathologies with dynamic patterns. 26,7% developed severe disease tending to have an ubiquitous lung involvement in lung ultrasound. In patients with need for intensive care unit a previously developed increase in B-lines, subpleural consolidations and pleural line irregularities was more common. A statistically significant association between change in B-lines as well as change in pleural line irregularities and development of severe disease was observed (p<0,01). CONCLUSION: The present study demonstrates that follow up lung ultrasound can be a powerful tool to track the evolution of disease and suggests that lung ultrasound is able to indicate an impending development of severe disease in COVID-19 patients.

COVID-19 in persons aged 70+ in an early affected German district: Risk factors, mortality and post-COVID care needs-A retrospective observational study of hospitalized and non-hospitalized patients.

BACKGROUND: Cohorts of hospitalized COVID-19 patients have been studied in several countries since the beginning of the pandemic. So far, there is no complete survey of older patients in a German district that includes both outpatients and inpatients. In this retrospective observational cohort study, we aimed to investigate risk factors, mortality, and functional outcomes of all patients with COVID-19 aged 70 and older living in the district of Tübingen in the southwest of Germany. METHODS: We retrospectively analysed all 256 patients who tested positive for SARS-CoV-2 in one of the earliest affected German districts during the first wave of the disease from February to April 2020. To ensure inclusion of all infected patients, we analysed reported data from the public health department as well as the results of a comprehensive screening intervention in all nursing homes of the district (n = 1169). Furthermore, we examined clinical data of all hospitalized patients with COVID-19 (n = 109). RESULTS: The all-cause mortality was 18%. Screening in nursing homes showed a point-prevalence of 4.6%. 39% of residents showed no COVID-specific symptoms according to the official definition at that time. The most important predictors of mortality were the need for inpatient treatment (odds ratio (OR): 3.95 [95%-confidence interval (CI): 2.00-7.86], p<0.001) and care needs before infection (non-hospitalized patients: OR: 3.79 [95%-CI: 1.01-14.27], p = 0.037, hospitalized patients: OR: 2.89 [95%-CI 1.21-6.92], p = 0.015). Newly emerged care needs were a relevant complication of COVID-19: 27% of previously self-sufficient patients who survived the disease were not able to return to their home environment after discharge from the hospital. CONCLUSION: Our findings demonstrate the importance of a differentiated view of risk groups and long-term effects within the older population. These findings should be included in the political and social debate during the ongoing pandemic to evaluate the true effect of COVID-19 on healthcare systems and individual functional status.