Inga Kniep

Bio: Inga Kniep is an academic researcher from University of Hamburg. The author has contributed to research in topics: Autopsy & Engineering. The author has an hindex of 3, co-authored 10 publications receiving 1221 citations.

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study.

Abstract: Background The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide However, little is known about the causes of death and the virus's pathologic features Objective To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests Design Prospective cohort study Setting Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19 Patients The first 12 consecutive COVID-19-positive deaths Measurements Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed Clinical data and medical course were evaluated Results Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2) Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively) Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart Limitation Limited sample size Conclusion The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it Primary funding source University Medical Center Hamburg-Eppendorf

First report from the German COVID-19 autopsy registry

Abstract: Autopsies are an important tool in medicine, dissecting disease pathophysiology and causes of death. In COVID-19, autopsies revealed e.g., the effects on pulmonary (micro)vasculature or the nervous system, systemic viral spread, or the interplay with the immune system. To facilitate multicentre autopsy-based studies and provide a central hub supporting autopsy centres, researchers, and data analyses and reporting, in April 2020 the German COVID-19 Autopsy Registry (DeRegCOVID) was launched.The electronic registry uses a web-based electronic case report form. Participation is voluntary and biomaterial remains at the respective site (decentralized biobanking). As of October 2021, the registry included N=1129 autopsy cases, with 69271 single data points including information on 18674 available biospecimens gathered from 29 German sites.In the N=1095 eligible records, the male-to-female ratio was 1·8:1, with peaks at 65-69 and 80-84 years in males and >85 years in females. The analysis of the chain of events directly leading to death revealed COVID-19 as the underlying cause of death in 86% of the autopsy cases, whereas in 14% COVID-19 was a concomitant disease. The most common immediate cause of death was diffuse alveolar damage, followed by multi-organ failure. The registry supports several scientific projects, public outreach and provides reports to the federal health authorities, leading to legislative adaptation of the German Infection Protection Act, facilitating the performance of autopsies during pandemics.A national autopsy registry can provide multicentre quantitative information on COVID-19 deaths on a national level, supporting medical research, political decision-making and public discussion.German Federal Ministries of Education and Research and Health.Hintergrund: Obduktionen sind ein wichtiges Instrument in der Medizin, um die Pathophysiologie von Krankheiten und Todesursachen zu untersuchen. Im Rahmen von COVID-19 wurden durch Obduktionen z.B. die Auswirkungen auf die pulmonale Mikrovaskulatur, das Nervensystem, die systemische Virusausbreitung, und das Zusammenspiel mit dem Immunsystem untersucht. Um multizentrische, auf Obduktionen basierende Studien zu erleichtern und eine zentrale Anlaufstelle zu schaffen, die Obduktionszentren, Forscher sowie Datenanalysen und -berichte unterstützt, wurde im April 2020 das deutsche COVID-19-Autopsieregister (DeRegCOVID) ins Leben gerufen.Methoden: Das elektronische Register verwendet ein webbasiertes elektronisches Fallberichtsformular. Die Teilnahme ist freiwillig und das Biomaterial verbleibt am jeweiligen Standort (dezentrales Biobanking). Im Oktober 2021 umfasste das Register N=1129 Obduktionsfälle mit 69271 einzelnen Datenpunkten, die Informationen über 18674 verfügbare Bioproben enthielten, die von 29 deutschen Standorten gesammelt wurden.Ergebnisse: In den N=1095 ausgewerteten Datensätzen betrug das Verhältnis von Männern zu Frauen 1,8:1 mit Spitzenwerten bei 65-69 und 80-84 Jahren bei Männern und >85 Jahren bei Frauen. Die Analyse der Sequenz der unmittelbar zum Tod führenden Ereignisse ergab, dass in 86 % der Obduktionsfälle COVID-19 die zugrunde liegende Todesursache war, während in 14 % der Fälle COVID-19 eine Begleiterkrankung war. Die häufigste unmittelbare Todesursache war der diffuse Alveolarschaden, gefolgt von Multiorganversagen. Das Register unterstützt mehrere wissenschaftliche Projekte, die Öffentlichkeitsarbeit und liefert Berichte an die Bundesgesundheitsbehörden, was zu einer Anpassung des deutschen Infektionsschutzgesetzes führte und die Durchführung von Obduktionen in Pandemien erleichtert.Interpretation: Ein nationales Obduktionsregister kann multizentrische quantitative Informationen über COVID-19-Todesfälle auf nationaler Ebene liefern und damit die medizinische Forschung, die politische Entscheidungsfindung und die öffentliche Diskussion unterstützen.Finanzierung: Bundesministerien für Bildung und Forschung und für Gesundheit.

Prospective postmortem evaluation of 735 consecutive SARS-CoV-2-associated death cases.

Abstract: Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. 84.1% (n = 618) were classified as COVID-19 deaths, 6.4% (n = 47) as non-COVID-19 deaths, 9.5% (n = 70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n = 283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%; n = 187). Thromboses were found in 39.2% (n = 62/158 cases), pulmonary embolism in 22.1% (n = 56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n = 618) represented COVID-19 deaths. Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.

COVID-19 lungs in post-mortem computed tomography.

Abstract: Post-mortem computed tomography (PMCT) is a rapid and noninvasive diagnostic tool for important contributions to the identification of pulmonary findings in the deceased with pneumonia, including cases of coronavirus disease 2019 (COVID-19). Although computed tomography (CT) shows a high sensitivity for pneumonia in living persons, it is relatively unspecific for COVID-19 pneumonia clinically. Typical CT findings for viral pneumonia therefore require confirmation by PCR tests (polymerase chain reaction tests), even if lung infections with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) show characteristic patterns, most frequently ground glass opacities (GGO) and a combination of GGO and air space consolidations. In the consecutive autopsy series of SARS-CoV‑2 deaths from Hamburg, Germany, the most frequent cause of death was and still is COVID-19 pneumonia. Typical findings were frequently found in the PMCT in SARS-CoV-2-associated deaths, which were taken into account when classifying the death as COVID-19.

[Postmortem imaging of the lung in cases of COVID-19 deaths].

Abstract: COVID-19 ist eine neu aufgetretene Viruserkrankung, die mit in der Computertomographie (CT) detektierbaren entzundlichen Lungenveranderungen einhergeht. Bislang wurde die postmortale CT (PMCT) nicht als Screening-Instrument fur die Evaluation von Todesfallen mit und ohne Obduktion eingesetzt, insofern ist ihre Validitat im Abgleich mit klinisch-radiologischen Erfahrungen zu prufen. Postmortale Computertomographie Die PMCT ist als methodische Innovation anzusehen, die fur Pneumonien noch nicht ausreichend evaluiert ist. Die CT hat im klinischen Alltag eine hohe Sensitivitat fur eine Pneumonie. Es wird gepruft, inwieweit postmortale Artefakte die PMCT in ihrer Aussagekraft beeintrachtigen. Noch gibt es kein standardisiertes Vorgehen bei der postmortalen radiologischen CT-Diagnose einer COVID-19-Erkrankung. Trotz postmortaler Artefakte kann das PMCT wertvolle Hinweise auf das Vorliegen einer Pneumonie mit interstitiellem Charakter geben, gerade ohne Obduktion. Die PMCT ist bei V. a. COVID-19-Pneumonie zur bildmorphologischen Einschatzung im Rahmen eines Monitorings von Todesfallen in der aktuellen Pandemiesituation sinnvoll.

Extrapulmonary manifestations of COVID-19.

Abstract: Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives.

Abstract: Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.

Neuropathology of patients with COVID-19 in Germany: a post-mortem case series.

Abstract: Summary Background Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. Methods In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. Findings 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. Interpretation In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. Funding German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).

Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19.

Abstract: An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1–7), and the ACE2/angiotensin-(1–7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1–7)/MAS may help attenuate organ injuries. SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.

Risk factors for severe and critically ill COVID-19 patients: A review.

Abstract: The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.