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Acute and sustained increase in endothelial biomarkers in COVID-19
  1. Raúl Méndez1,2,
  2. Paula González-Jiménez1,2,3,
  3. Ana Latorre2,
  4. Mónica Piqueras3,4,
  5. Leyre Bouzas1,2,3,
  6. Katheryn Yépez1,2,3,
  7. Ana Ferrando1,2,3,
  8. Enrique Zaldívar-Olmeda1,2,3,
  9. Antonio Moscardó5,
  10. Ricardo Alonso4,
  11. Soledad Reyes1,2,
  12. Rosario Menéndez1,2,3,6
  1. 1 Pneumology, La Fe University and Polytechnic Hospital, Valencia, Spain
  2. 2 Respiratory Infections, Health Research Institute La Fe, Valencia, Spain
  3. 3 Medicine, University of Valencia, Valencia, Spain
  4. 4 Laboratory, La Fe University and Polytechnic Hospital, Valencia, Spain
  5. 5 Platelet Function Unit, Health Research Institute La Fe, Valencia, Spain
  6. 6 Center for Biomedical Research Network in Respiratory Diseases (CIBERES), Madrid, Spain
  1. Correspondence to Dr Raúl Méndez, Pneumology, La Fe University and Polytechnic Hospital, Valencia 46026, Spain; mendez_rau{at}


Endothelial injury is related to poor outcomes in respiratory infections yet little is known in relation to COVID-19. Performing a longitudinal analysis (on emergency department admission and post-hospitalisation follow-up), we evaluated endothelial damage via surrogate systemic endothelial biomarkers, that is, proadrenomedullin (proADM) and proendothelin, in patients with COVID-19. Higher proADM and/or proendothelin levels at baseline were associated with the most severe episodes and intensive care unit admission when compared with ward-admitted individuals and outpatients. Elevated levels of proADM or proendothelin at day 1 were associated with in-hospital mortality. High levels maintained after discharge were associated with reduced diffusing capacity.

  • COVID-19
  • respiratory infection
  • viral infection
  • pneumonia

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  • RM and RM contributed equally.

  • Contributors Conceptualisation and study design—RaM and RoM. Patient enrolment and database management—RaM, PG-J, LB, KY, AF, EZ-O and SR. Laboratory analysis—AL, AM, RA and MP. Statistical analysis—RaM. Drafting the manuscript—RaM and RoM. Revision of manuscript and approval of the final version—all authors. RaM and RoM are the guarantors.

  • Funding This study was supported by: El Instituto de Salud Carlos III (ISCIII) through Project (PI17/01421) and Project (COV20/00385) (co-funded by the European Regional Development Fund/European Social Fund 'Investing in your future'); Sociedad Española de Neumología y Cirugía Torácica (SEPAR): 914/2019; 922/2019; Sociedad Valenciana de Neumología (SVN): 2019. RaM is the recipient of a Río Hortega grant supported by the Instituto de Salud Carlos III (ISCIII (CM19/00182)). PG-J is the recipient of a post-resident research grant supported by the Health Research Institute La Fe (2019-053-1).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.