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NATON case study on fatal VITT-like thrombosis
A recent case study from the NATON consortium presents the occurrence of a fatal cerebral venous sinus thrombosis and thrombocytopenia, resembling vaccine-induced immune thrombotic thrombocytopenia syndrome (VITT). It was diagnosed in a three-year-old boy who developed antibodies against the chemokine Platelet Factor 4 (PF4) after an adenovirus infection. VITT is typically associated with prior SARS-CoV-2 vaccination or the administration of heparin and is characterized by elevated levels of immunoglobulins targeting PF4.
The study posits that adenoviruses may engage with PF4 through charge complementarity, leading to the formation of antibodies and an ensuing immune response that can precipitate severe thrombotic complications. Postmortem examinations of the boy revealed anti-PF4 levels comparable to those seen in VITT cases, prompting the authors to advocate for targeted testing of anti-PF4 antibodies in instances of unexplained thrombosis and thrombocytopenia.
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Japan delegation visits NATON
To learn about the concept of the National Autopsy Network (NATON), a delegation of legal medicine specialists from six different institutes in Japan traveled to Germany for a three-day workshop. Following presentations by NATON coordinator Prof. Dr. Benjamin Ondruschka and NATON project manager Dr. Kristina Allgoewer, we engaged in discussions at the Institute of Legal Medicine at the University Medical Center Hamburg-Eppendorf with Prof. Dr. Toshikazu Kondo (Wakayama Medical University), Prof. Dr. Kazuya Ikematsu (Nagasaki University), Prof. Dr. Yoshiro Koda (Kurume University), Prof. Dr. Yosuke Usumoto (Kyushu University), Prof. Dr. Koichi Tsuneyama (Tokushima University), and Prof. Dr. Hideto Suzuki (Jichi Medical University) about future collaboration opportunities on NATON-related issues and the implementation of an autopsy network in Japan.
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NATON wishes you happy holidays
A busy and eventful year is coming to an end. 2024 has been marked by intensive work on joint concepts and applications, as well as valuable progress for which we would like to express our heartfelt gratitude.
During this thoughtful time of year, we would like to take a moment to pause and prepare together for the upcoming challenges. Your contribution and support are essential for the success of NATON, both now and in the new funding phase, and we look forward to working together on the continued development of the network in the upcoming year.
May the festive season bring you and your loved ones peace and joy. We wish you happy holidays and a successful start to the new year.
Your NATON Team
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Postmortem biopsies using VR technology
In cases involving highly infectious deceased individuals, postmortem tissue sampling for research purposes can be conducted through the closed body bag using CT-guided robotic control. The NATON methods platform is currently collaborating with a team from Hamburg University of Technology (TU Hamburg) to develop a new prototype that allows for precise remote control of the biopsy robot using virtual reality. At the Institute of Legal Medicine at the University Medical Center Hamburg-Eppendorf, we have now been able to test initial biopsy extractions using VR goggles and controllers.
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NATON publication on Long COVID: accumulation of spike protein
Researchers from Helmholtz Munich and LMU have identified a mechanism that may explain the neurological symptoms of Long COVID. The study, published in the journal Cell Host & Microbe under the title “Persistence of spike protein at the skull meningis-brain axis may contribute to the neurological sequelae of COVID-19,” reveals that the characteristic spike protein of the COVID-19 pathogen remains detectable within the skull long after infection. This persistent accumulation of the spike protein could contribute to the neurological long-term effects of COVID-19. The findings of the study open new avenues for the diagnosis and treatment of Long COVID. Tissue samples and the methodological expertise of NATON were utilized for the research.
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MITS-workshop in Hamburg
The potential of postmortem minimally invasive tissue sampling (MITS) for specimen collection under infection control risk conditions has been demonstrated, particularly during the COVID-19 pandemic. Especially for highly contagious infectious diseases where autopsies are not feasible or only partially possible, this method will continue to be an important alternative to conventional tissue sampling in the future. In a workshop hosted by the NATON methods platform, ultrasound expert Prof. Dr. Konrad Stock (Klinikum rechts der Isar at the Technical University of Munich) trained a team from the Institute of Legal Medicine at the University Medical Center Hamburg-Eppendorf and the Bernhard-Noch-Institute for Tropical Medicine in the MITS technique.
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NATON addresses COVID myths
In his sixth documentary on COVID-19, Eckart von Hirschhausen investigates rumors and myths surrounding the disease. Regarding claims in numerous YouTube videos that the COVID vaccine is responsible for deadly blood clots, Hirschhausen spoke with NATON coordinator Prof. Benjamin Ondruschka, the Director of the Institute of Legal Medicine at the University Medical Center Hamburg-Eppendorf. He and his team were among the first medical professionals worldwide to systematically perform autopsies on COVID-19 fatalities and discovered factors that helped save severely ill patients. The segment will air on Monday, November 18, 2024, at 8:15 PM on ARD and will be available in the media library starting November 16.
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4th NATON Quaterly Meeting 2024
In the final NATON Quaterly Meeting of 2024, neuropathologist PD Dr. Josefine Radke from the University Medical Center Greifswald delivered an engaging presentation about her research on deciphering the epigenetic, cellular, and spatial mechanisms involved in the progression of brain metastases from melanoma. This example once again underscored the importance of interconnected autopsy research. During the meeting, various topics were discussed, including the conditions of the NAREG ethics vote, the development of an S1 guideline for autopsies, updates from NATON’s public relations efforts, planning for the NUM Convention 2025, the current status of the NUM 3.0 application process, and recent cases from the daily practice of sectioning.
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NATON in video
How was our network established, what have we achieved so far, and what are the future tasks and perspectives for NATON? We are pleased to present our NATON video to you here. If the video does not display, please click on this link.
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3rd NATON Quaterly Meeting 2024
Since July, preparations for the 3rd funding phase of the Network of University Medicine NUM 3.0 have been underway. Accordingly, there was much to report at the 3rd NATON Quarterly Meeting 2024, which took place virtually on September 18, 2024. Among other topics, the research project eLEVATE was explained in detail, aiming to create five new use cases for NAREG, as well as the application phase for the NATON Research Infrastructure (FIS). Furthermore, the NATON team provided updates on the ongoing ethics procedure for NAREG and this year’s case-based fees. Finally, there was sufficient time to address and discuss all outstanding questions related to NUM 3.0 and other topics.
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NATON at GMDS 2024
As part of GMDS 2024, NATON had the opportunity to participate in a joint workshop with TMF and AKTIN. The focus was on the initial practical experiences with the Health Data Utilization Act (GDNG).
During the workshop, the key innovations of the GDNG were presented, and their relevance for medical research and practice was discussed. A central topic was the AKTIN infrastructure, which was explored in detail as part of a pilot project for the implementation of the GDNG. Additionally, initial insights into the application of the GDNG in the National Autopsy Register (NAREG) were shared. The discussions regarding experiences with the law in the ongoing ethics procedure were particularly valuable.
The workshop concluded with a panel discussion that addressed various perspectives on the practical implementation of the GDNG. We thank all participants for the lively exchange and the exciting insights.
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NATON at the 103rd DGRM annual conference in Potsdam
During the opening event of the 103rd annual conference of the German Society for Legal Medicine (DGRM), held this week in Potsdam, the National Autopsy Network (NATON) was mentioned. DGRM President Prof. Dr. Stefanie Ritz, Director of the Institute of Legal Medicine at Heinrich Heine University Düsseldorf, praised the collaboration between the various disciplines related to autopsies that is being promoted by NATON in her speech.
At the conclusion of the exciting three-day conference themed “Back and forward into the future,” NATON coordinator Prof. Dr. Benjamin Ondruschka from the Universitätsklinikum Hamburg-Eppendorf presented the results from the jointly developed online survey on autopsy practices, which the autopsy network conducted this spring with legal medicine, pathology, and neuropathology institutes. He emphasized the importance of actively informing both relatives and clinical colleagues about the benefits of autopsies.
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Study: chronic immune activation in the brain after COVID-infection
A new study from the NATON consortium has found evidence of persistent activation of the innate immune system in the brains of individuals following a COVID-19 infection that occurred some time ago. Post-mortem tissue samples collected through the National Autopsy Network contributed to the findings published in the prestigious journal Acta Neuropathologica. In the brains of individuals who had contracted COVID-19, fully recovered, and later died from other causes, researchers from Freiburg, Hamburg, and Basel discovered numerous clusters of cells, known as microglial nodules, which indicate chronic immune activation and do not heal completely, resembling a scar. These immunological changes could contribute to the long-term neurological complaints experienced by some patients after SARS-CoV-2 infection.
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Positive Vote in the NAREG ethics procedure
We are pleased to announce that we have received a positive vote in the NAREG ethics procedure! This is an important milestone that opens the door for us to address virtually any use case. A key aspect of this achievement is that it is the first initiative following the new Health Data Utilization Act (GDNG), marking a pioneering effort on our part.
The vote comes with two conditions, one of which is crucial. We hope to clarify this in a further statement to the ethics committees.
Subsequently, in accordance with the GDNG, we will need to conduct a data protection impact assessment. After that, we will initiate the secondary votes from all participating centers that could not formally engage in the coordinated procedure. Simultaneously, we are working on the live launch of NAREG and will keep you updated on all forthcoming developments.
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2nd NATON Quarterly Meeting 2024
The 2nd NATON Quarterly Meeting 2024 took place virtually on June 19, 2024. The meeting began with a short presentation from the research infrastructure RACOON, the radiology collaboration within the Network of University Medicine, which includes all German university hospitals. The project team led by Prof. Penzkofer and Dr. Bucher provided updates on the establishment of the infrastructure, past achievements, and future plans. They also invited the entire NATON network to the AI Symposium on September 5 and 6 in Frankfurt am Main. Following the presentation, there was an active discussion about potential collaboration opportunities and the applicability of experiences with imaging data in radiology to imaging data in pathology. This was followed by a brief overview of the changes brought by the Health Data Utilization Act (GDNG) to the National Autopsy Register (NAREG). Additionally, the current status of the coordinated ethics procedure was explained. Finally, there was an initial summary of the NATON survey on autopsy practices in Germany, along with preliminary information regarding the new funding phase of the Network of University Medicine (NUM 3.0).
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NATON in Okayama, Japan
At the 108th “Annual Meeting of the Japanese Society of Legal Medicine” in Okayama, NATON coordinator Prof. Dr. Benjamin Ondruschka (UKE) presented the National Autopsy Network. The title of his presentation was “Fueling the largest autopsy network worldwide – past, present, and future of collaborative post-mortem research.” The presentation covered the history, achievements, and future goals of the autopsy network, addressing potential applications and collaboration opportunities with Japanese colleagues. This sparked great interest among the conference participants and led to lively discussions.
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NATON at the DGP annual conference 2024
From May 23 to 25, this year’s annual conference of the German Society for Pathology e.V. took place at the Science Center in Munich.
On the first day, there was a contribution by Prof. Peter Boor in the session on Network Structures, highlighting how NATON integrates into the structures of the NUM.
The second day featured the annual networking meeting @ DGP. For the past three years, NATON has been allocated a slot at the annual conference for discussions and exchanges with network partners. The session began with a scientific presentation by Ines Gütgemann from Bonn University Hospital on “Neuropilin 1 (NRP1) and Neuropilin 2 (NRP2) in fatal COVID-19.” This was followed by an in-depth examination and broad discussion on the Health Data Utilization Act (GDNG) and its impact on NAREG.
We would like to thank all participants for the engaging exchange and active discussions.
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Registertage 2024
The Registertage 2024, organized by the TMF Technology and Methods Platform for Connected Medical Research e.V., took place from May 16 to 17 in Berlin. The National Autopsy Network was present with the National Autopsy Register (NAREG) to contribute to the Health Data Utilization Act (GDNG). After a brief introduction to the establishment of the register and the successes of DeRegCOVID, the individual paragraphs of the GDNG were examined in detail, demonstrating how the new legislation affects the register.
In addition to the GDNG, other politically relevant topics included the Register Law and the European Health Data Space (EHDS). Georg Schmidt, chairman of the Working Group of Medical Ethics Committees (AKEK), provided key insights. He announced that he would abandon the coordinated ethics procedures, which have not proven effective in practical implementation, in favor of developing conditions for “One Study – One Vote,” whereby a single vote from an ethics committee would suffice for multicenter studies (lead principle). This initiative aims to improve the framework conditions for registers and also announces a submission portal for registers/studies, uniform application documents, defined evaluation criteria, and the binding nature of AKEK decisions.
On the second day of the Register Days, networking, participation, and quality assurance in registers were the main focus of the sessions. Overall, the Register Days once again provided a valuable platform for exchanging and discussing current topics and challenges in register research.
Thank you to the TMF for organizing this event. For more information, please visit here and on Twitter/X @tmf_eV and @NATON_network.
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NATON Statement on the German Medical Licensing Act (ÄApprO)
Autopsies are and remain the gold standard in post-mortem diagnostics. No other examination method allows for such a complete investigation, understanding, and tracing of final disease states, injuries, pathophysiologies and mechanisms, as well as causes of death, as an autopsy does. The removal of pathological-anatomical case demonstrations in the draft of the German Medical Licensing Act (ÄApprO) is incomprehensible to us. We strongly recommend on our part to correct this change. For this reason, NATON advocates for the Professional Association of German Pathologists in issuing a renewed statement by providing a Letter of Support. Only by maintaining the case demonstrations can future physicians experience and learn about the opportunities that autopsies provide.
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FAS-article: corpses as lifesavers
In the Frankfurter Allgemeine Sonntagszeitung dated April 28, 2024, medical journalist Ragnhild Schweitzer writes about the importance of autopsies in the research of new diseases and their effects on the entire body. The fact that corpses in Germany are increasingly subjected to only superficial examinations is seen as a missed opportunity. The National Autopsy Network (NATON) has provided statements for the article and is quoted multiple times.
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Effects of COVID-19 on the brain
Do neurological symptoms in COVID-19 cases arise from an infection of the brain, or are they a consequence of inflammation in the rest of the body? A study from the NATON consortium, published in Nature Neuroscience, provides evidence for the latter theory. The research team, led by NATON project coordinator Helena Radbruch (Charité), analyzed various areas of the brains of 21 individuals who had died in the hospital, mostly in the intensive care unit, due to severe COVID-19 infections. For comparison, nine patients who succumbed to other conditions after intensive medical treatment were included. No SARS-CoV-2 infected nerve cells were found. However, some nerve cells, particularly in the nuclei of the vagus nerve, appear to respond to inflammation in the rest of the body— for example, by activating the interferon signaling pathway. ‘In this way, inflammation is, in a sense, transmitted from the body to the brain, which can disrupt its function,’ said Radbruch.
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NATON at the 4th DGRM Spring Conference Digital
At the 4th Spring Conference of the German Society of Legal Medicine ‘Digital,’ researchers from the NATON consortium (University Medical Center Hamburg-Eppendorf) presented the first three contributions: Malin Lutter reported on the imaging morphological lung pathology in COVID-19, comparing clinical and postmortem computed tomography. Fabian Heinrich presented a postmortem study on concerning SARS-CoV-2 variants. Kristina Allgoewer introduced an analysis of the impact of the COVID-19 pandemic on the entry of corpses into a legal medicine institute. We will report shortly on the publication of the results.
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Development and progress of NATON
A new review article in “Die Pathologie” presents the development and progress of the National Autopsy Network. In April 2020, pathology, neuropathology, and legal medicine first came together to form the german Register for COVID-19 Autopsies (DeRegCOVID). From this successful register, the German Research Network for Autopsies in Pandemics (DEFEAT PANDEMIcs) quickly emerged, which has evolved into the National Autopsy Network (NATON). To date, 33 university and 6 non-university centers are involved in DeRegCOVID and NATON, including two international centers from Austria, which joined for the first time in 2023. The autopsy network has made significant contributions to understanding the pathophysiology of COVID-19, emphasizing the high value of interconnected, autopsy-based research. With the National Autopsy Register (NAREG), the successful work is set to continue for additional applications beyond COVID-19.
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1st NATON Quarterly Meeting 2024
On February 28, the first NATON Quarterly Meeting of 2024 was held virtually. Following a presentation by Dr. Emanuel Wyler from the Max Delbrück Center for Molecular Medicine (MDC) on the topic of ‘Spatiotemporally resolved transcriptome analyses with single-cell resolution on autopsy samples,’ the project coordinators provided updates on the recent in-person meeting in Berlin, the NUM Convention, and the meeting on NUM evaluation. Additionally, there was an update on the coordinated ethics procedure for the National Autopsy Register (NAREG) and a call from the NATON Methods Platform for an online survey on autopsy practices in Germany, Austria, and Switzerland. A recording of the meeting can be found in the February newsletter.
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Ultrasound-guided minimally invasive autopsy in the intensive care unit
A feasibility study conducted by an interdisciplinary team from the NATON consortium on the temporal efficiency, infection control aspects, and quality of tissue samples from ultrasound-guided minimally invasive autopsies performed directly at the bedside of COVID-19 decedents can be found here.
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COVID mechanisms in obesity and diabetes mellitus
In a new publication in Heliyon, researchers from the NATON consortium have examined the increased risk and underlying mechanisms of COVID-19 disease in individuals with obesity and pre-existing diabetes mellitus.
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NATON at the NUM Convention
An example for Europe and the world: NATON was one of the few selected projects from the Network of University Medicine (NUM) that had the opportunity to present itself to an audience from medicine, science, healthcare, politics, and industry at the NUM Convention in Berlin.
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2nd NATON Network Meeting – Thank You!
We would like to thank all participants who gathered in large numbers from across Germany at Charité for the 2nd NATON Network Meeting despite the snowy chaos! Following an interesting keynote from the Paul-Ehrlich Institute and brief presentations on research projects from the NATON consortium, we were able to discuss various topics regarding the future direction of the network in a World Café format.
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Program for the 2nd NATON Network Meeting
NATON is kicking off the new year productively: final preparations for the network meeting on January 16, 2024, in Berlin are in progress. You can find the current agenda here. Last-minute registrants can still sign up until January 14 using the following link. We look forward to your attendance!
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NATON wishes you happy holidays
Dear project partners and interested parties, the past year has been marked by shared successes, engaged exchange, and valuable progress, for which we would like to express our heartfelt thanks. Your contribution and support are essential to the success of NATON, and we eagerly anticipate collaborating further to enhance the network in the upcoming year. May this festive season bring you and your loved ones peace and joy. We wish you happy holidays and a successful start to the new year!
Your NATON Team
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NUM Symposium at UKE
Twelve current projects from the Network of University Medicine (NUM) at the University Medical Center Hamburg-Eppendorf (UKE) presented their project progress yesterday and discussed opportunities for mutual networking. NATON was represented by two presentations: one introducing the project and a second discussing the project management of NATON, which was highlighted as particularly exemplary by the local NUM office.
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Postmortem CT in COVID-19-decedents
A new NATON study on the applicability of established clinical diagnostic computed tomography (CT) criteria for COVID-19 infections to postmortem computed tomography can be found here:
Lutter M, Kniep I, Ondruschka B, Heinemann A. Pulmonale Befunde in der postmortalen Computertomographie bei COVID-19-assoziierten Todesfällen. Rechtsmedizin 2023. https://doi.org/10.1007/s00194-023-00667-4.
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4th NATON Quarterly Meeting 2023
The final NATON Quarterly Meeting of 2023 took place on November 22 from 2 PM to 4 PM and began with a lecture by Prof. Dr. Birgit Sawitzki from the Berlin Institute of Health titled ‘Rewired type I IFN signaling is linked to age-dependent differences in COVID-19.’ Afterwards, participants discussed the advancements of the three work packages, along with updates from NAREG and NATON, and deliberated over potential new project initiatives. The new dates and access links for the quarterly meetings in 2024 have already been circulated within the network.
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Registration for the 2nd NATON Network Meeting
On January 16, 2024, the 2nd NATON Network Meeting is scheduled to be held in person at Charité Berlin, beginning at 1 PM. More information about the event program will follow, but you can register here already. Attendance is free of charge.
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NATON at PneumoVisions 2023
At PneumoVisions 2023 in Berlin, NATON was represented with a presentation on postmortem COVID-19 research.
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NATON in Japan
The National Autopsy Network was presented at the Joint Meeting of the 40th Cigoku-Shikoku District Conference of the Japanese Society of Legal Medicine and the 100th Anniversary Conference of the Department of Legal Medicine, Okayama University in Okayama, Japan.
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New NATON-protocol for MITS
A protocol for ultrasound-guided, minimally invasive tissue sampling (MITS) can be found in this new publication from the NATON consortium:
Schädler, J., Azeke, A.T., Ondruschka, B. et al. Concordance between MITS and conventional autopsies for pathological and virological diagnoses. Int J Legal Med (2023). https://doi.org/10.1007/s00414-023-03088-w
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NATON on Bluesky
The National Autopsy Network is now present on the social media platform Bluesky. Follow us at naton.bsky.social.
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New Review from the NATON Consortium 2023
A new review from the NATON consortium in Nature Microbiology discusses how autopsies have contributed to significant insights into the pathophysiology of COVID-19.
Heinrich, F., Mertz, K. D., Glatzel, M., Beer, M. & Krasemann, S. Using autopsies to dissect COVID-19 pathogenesis. Nat Microbiol 1–9 (2023). http://doi.org/10.1038/s41564-023-01488-7
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3. NATON Meeting
On Wednesday, 27.09.2023 the 3rd NATON Quarterly Meeting 2023 took place. It started with a presentation by Dr. Stephanie Stanelle-Bertram (Leibniz Institute of Virology) on “Elucidation of the pathomechanisms of COVID-19 by autopsy samples”. Other agenda items included the current status of the NAREG ethics submission, the submitted manuscript on postmortem cases after vaccination, case fees in NATON, and the evaluation report planned by the Network University Medicine along with the NUM Convention scheduled for January 2024.
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NATON at ICN 2023
At the International Congress of Neuropathology (ICN) in Berlin, NATON participants met with interested researchers from around the world in a designated session including two presentations and an engaging discussion.
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NATON at the DGRM Annual Conference 2023
With two lectures and a poster presentation, the National Autopsy Network (NATON) was represented at the annual conference of the German Society for Legal Medicine in Jena.
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NATON at the ESCV Congress 2023
At the meeting of the European Society for Clinical Virology in Milan, scientists from the NATON consortium presented new research findings in a lecture and a poster presentation.
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Start of the coordinated ethics procedure
On August 16, the NAREG project was successfully submitted to 24 participating ethics committees.
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NATON 1.0 approved
The DLR has approved the application for the continuation of NATON 1.0 until June 2025. This means that data reporting fees can officially continue to be paid out (as usual at the end of the year)!
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Registertage 2023
The Registertage 2023 of the TMF Technology and Methods Platform for Networked Medical Research e. V. are over. DeRegCOVID was represented with a contribution on the topic of harmonization, from which not only clear demands on the register law presented by the Federal Ministry of Health emerged, but in which above all the transition to a National Autopsy Register (NAREG) was addressed.
The conference in Berlin, which brought together more than 160 experts from the healthcare sector, is considered “an important platform for the exchange and discussion of current issues and challenges in registry research. The conference shows perspectives on how patient-based registries can develop further against the background of new political and technological framework conditions and thus be used even more beneficially for health services research.”
At the “Innovationspreis Medizinische Register” (Innovation Award for Medical Registries), which was awarded by ]init[, DeRegCOVID was able to hold its own against more than 10 other registries in the preliminary round, but unfortunately did not make it onto the winners’ podium in the final.
Many thanks to all who made the Registertage a valuable place for networking and exchange again this year!
More information about the Registertage can be found here and on Twitter @tmf_eV or @DeRegCOVID.
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Thanks for coming!
Forensic physicians, pathologists and neuropathologists from all over Germany met for two days at the UKE in Hamburg for the kick-off meeting of the National Autopsy Network (NATON) and discussed and developed new ideas during lectures and workshops. We would like to thank all participants and are already looking forward to the next meeting!
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NATON Kick Off @ UKE
The University Medical Center Hamburg-Eppendorf invites you to the first presence meeting on 20/21 April! Further information and the registration form can be found on the event page.
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New Paper of the NATON Consortium 2023
Heinrich et al., 2023: New postmortem perspective on emerging SARS-CoV-2 variants of concern, Germany. Emerg Infect Dis doi: 10.3201/eid2903.221297
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Start of NATON 2.0
As of 01.01.2023, the NATON project will run as a sub-project of the NUM infrastructure line.
