Extract
Approximately 20% of symptomatic patients with SARS-CoV-2 infection progress to severe coronavirus disease (COVID-19) with critical hypoxemia fulfilling the criteria of acute respiratory distress syndrome (ARDS). Consistent with the classic features of ARDS, severe COVID-19 is characterised by ground glass opacities in CT imaging and diffuse alveolar damage post mortem [5] suggesting permeability-type lung edema as driver of respiratory failure. Consistent with this concept, autopsy findings show severe lung endothelial injury in patients who succumbed to COVID-19 [1].
Abstract
Plasma of COVID-19 patients induces pulmonary microvascular barrier failure which increases with disease severity. Here, we report a versatile high-throughput screening platform to test for involved plasma mediators and the therapeutic potential of barrier stabilising compounds.
Acknowledgements
The authors thank the Advanced Medical Bioimaging Core Facility (AMBIO) of Charité—Universitätsmedizin Berlin (Berlin, Germany) for the support in acquisition of the imaging data.
Footnotes
Author Contributions: LM, ACH, MW, SH, and WMK conceived study; LM, SW, BG, DF, PDS, MD, MCB, VMC and SaS performed experiments and analysed the data; HMR, FK, NS, FB, ET, SzS, JN, MT, TTB and se provided and collected samples, FK, MW led the clinical study, LM, ACH, MW, SH, and WMK wrote manuscript, all authors revised and approved manuscript.
Support statement: LES is supported by DFG (SFB-TR84), BMBF (PROVID), Berlin University Alliance (BUA, PreEP_Corona); ACH and SH are supported by Berlin University Alliance GC2 Global Health (Corona Virus Pre Exploration Project), BMBF (RAPID, alvBarriere-COVID-19, PROVID), DFG (SFB-TR 84), BIH, Charite 3R, and Charité-Zeiss MultiDim; MW is supported by DFG (SFB-TR84) and BMBF (CAPSyS-FKZ, Phage4Cure-FKZ, SYMPATH, PROVID); WMK is supported by grants-in-aid from the Ministry of Education and Research (BMBF) (SYMPATH, PROVID), the German Research Foundation (DFG) (DFG 1218/9-1, 1218/11-1, SFB-TR84), the German Centre for Cardiovascular Research (DZHK), and the Canadian Institutes for Health Resarch (CIHR). Berlin University Alliance; Grant: Corona Virus Pre Exploration Project, PreEP Corona; Charité Universitätsmedizin Berlin; DOI: http://dx.doi.org/10.13039/501100002839; Bundesministerium für Bildung und Forschung; DOI: http://dx.doi.org/10.13039/501100002347; Grant: CAPSyS-FKZ, PROVID, Phage4Cure-FKZ, RAPID, SYMPATH, alvBarriere-COVID-19; Canadian Institutes of Health Research; DOI: http://dx.doi.org/10.13039/501100000024; Charité-Zeiss MultiDim; Deutsches Zentrum für Herz-Kreislaufforschung; DOI: http://dx.doi.org/10.13039/100010447; Berlin Institute of Health; Deutsche Forschungsgemeinschaft; DOI: http://dx.doi.org/10.13039/501100001659; Grant: 1218/11-1, 1218/9-1, SFB-TR84.
Conflict of interest: Dr. Laura Michalick has nothing to disclose.
Conflict of interest: Dr. Weidenfeld has nothing to disclose.
Conflict of interest: Benjamin Grimmer has nothing to disclose.
Conflict of interest: Dr. Fatykhova has nothing to disclose.
Conflict of interest: Dr. Solymosi has nothing to disclose.
Conflict of interest: Dr. Behrens has nothing to disclose.
Conflict of interest: Dr. Dohmen has nothing to disclose.
Conflict of interest: Markus Brack has nothing to disclose.
Conflict of interest: Sabrina Schulz has nothing to disclose.
Conflict of interest: Elisa Thomasch has nothing to disclose.
Conflict of interest: Dr. Szandor Simmons has nothing to disclose.
Conflict of interest: Dr. Müller-Redetzky has nothing to disclose.
Conflict of interest: Dr. Suttorp has nothing to disclose.
Conflict of interest: Dr. Kurth has nothing to disclose.
Conflict of interest: Jens Neudecker, MD, PhD, has nothing to disclose.
Conflict of interest: Dr. Tönnies has nothing to disclose.
Conflict of interest: Dr. Bauer has nothing to disclose.
Conflict of interest: Dr. Eggeling has nothing to disclose.
Conflict of interest: Dr. Corman has nothing to disclose.
Conflict of interest: Dr. Andreas Hocke has nothing to disclose.
Conflict of interest: Dr. Witzenrath reports grants and personal fees from Actelion, grants and personal fees from Bayer Health Care, grants and personal fees from Biotest, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Noxxon, grants and personal fees from Pantherna, grants from Quark Pharma, grants and personal fees from Silence Therapeutics, grants from Takeda Pharma, grants and personal fees from Vaxxilon, personal fees from Aptarion, personal fees from Astra Zeneca, personal fees from Berlin Chemie, personal fees from Chiesi, personal fees from Glaxo Smith Kline, personal fees from Novartis, personal fees from Sinoxa, personal fees from Teva, outside the submitted work; In addition, Dr. Witzenrath has a patent Means for inhibiting the expression of ANG2 US8829179B2 issued.
Conflict of interest: Dr. Hippenstiel has nothing to disclose.
Conflict of interest: Dr. Kuebler reports grants from Ministry of Education and Research (BMBF), grants from German Research Foundation (DFG), grants from German Centre for Cardiovascular Research (DZHK), grants from Canadian Institutes for Health Resarch (CIHR), during the conduct of the study.
- Received June 18, 2020.
- Accepted October 11, 2020.
- Copyright ©ERS 2020
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.