Helene Häberle

Bio: Helene Häberle is an academic researcher from University of Tübingen. The author has contributed to research in topics: Medicine & Sepsis. The author has an hindex of 8, co-authored 15 publications receiving 407 citations.

The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation.

Abstract: The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy.

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial

Abstract: Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1–4.9 h) in the intervention group and 2.0 h (0.4–5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021.

Abstract: Background Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications. Methods We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements. Results The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care. Conclusion The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.

Abstract: Background Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications. Methods We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements. Results The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care. Conclusion The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19.

Abstract: Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.

COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.

Abstract: COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1–4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments. Single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe COVID-19 infection.