Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19 PMID: 33824483

Target-related Cytokines

2026-09-23

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

Nat Rev Immunol. 2021 May;21(5):319-329. doi: 10.1038/s41577-021-00536-9.

Aldo Bonaventura ¹ ² ³ , Alessandra Vecchié ⁴ ⁵ , Lorenzo Dagna ⁶ ⁷ , Kimberly Martinod ⁸ , Dave L Dixon ⁴ ⁹ , Benjamin W Van Tassell ⁴ ⁹ , Francesco Dentali ¹⁰ , Fabrizio Montecucco ¹¹ ¹² , Steffen Massberg ¹³ ¹⁴ , Marcel Levi ¹⁵ , Antonio Abbate ⁴

Affiliations

1. Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA. [email protected].
2. First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy. [email protected].
3. Department of Internal Medicine, ASST dei Sette Laghi, Varese, Italy. [email protected].
4. Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
5. Department of Internal Medicine, ASST dei Sette Laghi, Varese, Italy.
6. Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
7. Vita-Salute San Raffaele University, Milan, Italy.
8. Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
9. Department of Pharmacotherapy and Outcome Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.
10. Department of Medicine and Surgery, Insubria University, Varese, Italy.
11. IRCCS Ospedale Policlinico San Martino Genova - Italian Cardiovascular Network, Genoa, Italy.
12. First Clinic of Internal Medicine, Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.
13. Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) e.V., Partner Site Munich Heart Alliance, Munich, Germany.
14. Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.
15. Department of Medicine and Cardio-metabolic Programme - NIHR UCLH/UCL BRC, University College London Hospitals NHS Foundation Trust, London, UK.

Abstract

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the Lungs. Here, we propose that SARS-CoV-2 Infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 Infection. The growing understanding of SARS-CoV-2 Infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.