Intracranial hemorrhage in COVID-19 patients during extracorporeal membrane oxygenation for acute respiratory failure: a nationwide register study report
Authors: von Stillfried Saskia , Bülow Roman David , Röhrig Rainer , Meybohm Patrick , Boor Peter ,   for the German Registry of COVID-19 Autopsies (DeRegCOVID), DeRegCOVID Collaborators#, Böcker Jana , Schmidt Jens , Tholen Pauline , Majeed Raphael , Wienströer Jan , Weis Joachim , Bremer Juliane , Knüchel Ruth , Breitbach Anna , Cacchi Claudio , Freeborn Benita , Wucherpfennig Sophie , Spring Oliver , Braun Georg , Römmele Christoph , Märkl Bruno , Claus Rainer , Dhillon Christine , Schaller Tina , Sipos Eva , Hirschbühl Klaus , Wittmann Michael , Kling Elisabeth , Kröncke Thomas , Heppner Frank L. , Meinhardt Jenny , Radbruch Helena , Streit Simon , Horst David , Elezkurtaj Sefer , Quaas Alexander , Göbel Heike , Hansen Torsten , Titze Ulf , Lorenzen Johann , Reuter Thomas , Woloszyn Jaroslaw , Baretton Gustavo , Hilsenbeck Julia , Meinhardt Matthias , Pablik Jessica , Sommer Linna , Holotiuk Olaf , Meinel Meike , Mahlke Nina , Esposito Irene , Crudele Graziano , Seidl Maximilian , Amann Kerstin U. , Coras Roland , Hartmann Arndt , Eichhorn Philip , Haller Florian , Lange Fabienne , Schmid Kurt Werner , Ingenwerth Marc , Rawitzer Josefine , Theegarten Dirk , Birngruber Christoph G. , Wild Peter , Gradhand Elise , Smith Kevin , Werner Martin , Schilling Oliver , Acker Till , Gattenlöhner Stefan , Stadelmann Christine , Metz Imke , Franz Jonas , Stork Lidia , Thomas Carolina , Zechel Sabrina , Ströbel Philipp , Wickenhauser Claudia , Fathke Christine , Harder Anja , Ondruschka Benjamin , Dietz Eric , Edler Carolin , Fitzek Antonia , Fröb Daniela , Heinemann Axel , Heinrich Fabian , Klein Anke , Kniep Inga , Lohner Larissa , Möbius Dustin , Püschel Klaus , Schädler Julia , Schröder Ann-Sophie , Sperhake Jan-Peter , Aepfelbacher Martin , Fischer Nicole , Lütgehetmann Marc , Pfefferle Susanne , Glatzel Markus , Krasemann Susanne , Matschke Jakob , Jonigk Danny , Werlein Christopher , Schirmacher Peter , Domke Lisa Maria , Hartmann Laura , Klein Isabel Madeleine , Schwab Constantin , Röcken Christoph , Friemann Johannes , Langer Dorothea , Roth Wilfried , Strobl Stephanie , Rudelius Martina , Stock Konrad Friedrich , Weichert Wilko , Delbridge Claire , Kasajima Atsuko , Kuhn Peer-Hendrik , Slotta-Huspenina Julia , Weirich Gregor , Barth Peter , Wardelmann Eva , Schnepper Alexander , Evert Katja , Büttner Andreas , Manhart Johannes , Nigbur Stefan , Bittmann Iris , Fend Falko , Bösmüller Hans , Granai Massimo , Klingel Karin , Warm Verena , Steinestel Konrad , Umathum Vincent Gottfried , Rosenwald Andreas , Kurz Florian , Vogt Niklas 
Published: March 2022

Abstract
Background
In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID).

Methods
The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites.

Findings
The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency.

Interpretation
Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.