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.

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.

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.

Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia.

Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2 peptides to the patients' HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Toward clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19.

Severe SARS-CoV-2 Infection Inhibits Fibrinolysis Leading to Changes in Viscoelastic Properties of Blood Clot: A Descriptive Study of Fibrinolysis in COVID-19.

BACKGROUND: Accumulating evidence indicates toward an association between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and procoagulatory state in blood. Thromboelastographic investigations are useful point-of-care devices to assess coagulation and fibrinolysis. OBJECTIVES: We investigated the hypothesis that the procoagulatory state in COVID-19 patients is associated with impaired fibrinolysis system. METHODS: Altogether, 29 COVID-19 patients admitted to normal wards or to the intensive care unit (ICU) were included in this descriptive study. Whole blood samples were investigated by thromboelastography to assess coagulation and fibrinolysis. Additionally, standard routine coagulation testing and immunoassays for factors of fibrinolysis as plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), plasminogen activity and α2-antiplasmin (A2AP) were performed. RESULTS: A significantly increased lysis resistance and a significantly longer time of lysis after adding tissue plasminogen activator were observed in blood samples from ICU COVID-19 patients compared with healthy controls (maximal lysis: 3.25 ± 0.56 vs. 6.20 ± 0.89%, p = 0.0127; lysis time: 365.7 ± 44.6 vs. 193.2 ± 16.3 seconds, p = 0.0014). PAI-1 activity was significantly higher in plasma samples of ICU COVID-19 patients (PAI-1: 4.92 ± 0.91 vs. 1.28 ± 0.33 U/mL, p = 0.001). A positive correlation between the activity of PAI-1 and lysis time of the formed clot (r = 0.70, p = 0.0006) was observed. CONCLUSION: Our data suggest that severe SARS-CoV-2 infection is associated with impaired fibrinolytic activity in blood, where fibrinolytic inhibitors are elevated leading to an increased resistance to clot lysis. Thromboelastography could offer a tool to investigate the contribution of the fibrinolytic status to the procoagulatory condition in COVID-19.

Impact of the COVID-19 pandemic on an interdisciplinary endoscopy unit in a German "hotspot" area: a single center experience.

BACKGROUND AND STUDY AIMS: Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19), has posed a pandemic threat to global health and has challenged health care system in all affected countries. PATIENTS AND METHODS: This is a combined study including a descriptive part about the changes in the daily work routine of an Interdisciplinary Endoscopic Unit (IEU) and a prospective analysis of patients tested positive for SARS-CoV-2 who required endoscopic interventions. Conclusively, we present the finding of a point-prevalence analysis in the staff of the IEU. RESULTS: We present effects of the COVID-19-related restructuring of processes in our interdisciplinary endoscopy unit (IEU) with respect to cancelation of examinations, relocation of staff to other departments, impact of SARS-CoV-2 on medical staff of the IEU, and supply of protective clothing. Additionally, we analyzed the cohort of COVID-19 patients: Sixteen endoscopic interventions were done in ten patients. In all patients with confirmed infection with SARS-CoV-2, emergency endoscopies were required for relevant bleeding situations. Re-endoscopies were required only in critically ill COVID-19 patients. CONCLUSIONS: The restructuring of processes in the IEU was feasible in short time, effective, and can also be applied broadly at least in developed countries [Garbe et al. in Gastroenterology 159:778-780, 2020; Repici A, Pace F, Gabbiadini R, Colombo M, Hassan C, Dinelli M, Group IG-CW, Maselli R, Spadaccini M, Mutignani M, Gabbrielli A, Signorelli C, Spada C, Leoni P, Fabbri C, Segato S, Gaffuri N, Mangiavillano B, Radaelli F, Salerno R, Bargiggia S, Maroni L, Benedetti A, Occhipinti P, De Grazia F, Ferraris L, Cengia G, Greco S, Alvisi C, Scarcelli A, De Luca L, Cereatti F, Testoni PA, Mingotto R, Aragona G, Manes G, Beretta P, Amvrosiadis G, Cennamo V, Lella F, Missale G, Lagoussis P, Triossi O, Giovanardi M, De Roberto G, Cantu P, Buscarini E, Anderloni A, Carrara S, Fugazza A, Galtieri PA, Pellegatta G, Antonelli G, Rosch T, Sharma P (2020) Endoscopy units and the COVID-19 Outbreak: a Multi-Center Experience from Italy. Gastroenterology;]. The endoscopy-related rate of SARS-CoV-2 infection of staff is low, but supply of protective equipment is crucial for this. Endoscopic procedures in COVID-19 patients were not directly related to SARS-CoV-2 infection, but to other underlying diseases or typical complications of long-term ICU treatment.