Immunothrombotic Dysregulation in COVID-19 Pneumonia is Associated with Respiratory Failure and Coagulopathy

Nicolai, Leo; Leunig, Alexander; Brambs, Sophia; Kaiser, Rainer; Weinberger, Tobias; Weigand, Michael; Muenchhoff, Maximilian; Hellmuth, Johannes C.; Ledderose, Stephan; Schulz, Heiko; Scherer, Clemens; Rudelius, Martina; Zoller, Michael; Höchter, Dominik J.; Keppler, Oliver T.; Teupser, Daniel; Zwißler, Bernhard; Bergwelt-Baildon, Michael; Kääb, Stefan; Massberg, Steffen; Pekayvaz, Kami und Stark, Konstantin (28. Juli 2020): Immunothrombotic Dysregulation in COVID-19 Pneumonia is Associated with Respiratory Failure and Coagulopathy. In: Circulation, Bd. 142, Nr. 12: S. 1176-1189

Abstract

Background: SARS-CoV-2 infection causes severe pneumonia (COVID-19), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood. In addition, a systemic prothrombotic phenotype has been reported in COVID-19 patients. Methods: A total of 62 subjects were included in our study (n=38 patients with RT-PCR confirmed COVID-19 and n=24 non-COVID-19 controls). We performed histopathological assessment of autopsy cases, surface-marker based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions as well as coagulation tests. Results: We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis. We show that in COVID-19 inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin. COVID-19 patients also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood, which changes with disease severity. Whereas cases of intermediate severity show an exhausted platelet and hyporeactive neutrophil phenotype, severely affected COVID-19 patients are characterized by excessive platelet and neutrophil activation compared to healthy controls and non-COVID-19 pneumonia. Dysregulated immunothrombosis in SARS-CoV-2 pneumonia is linked to both ARDS and systemic hypercoagulability. Conclusions: Taken together, our data point to immunothrombotic dysregulation as a key marker of disease severity in COVID-19. Further work is necessary to determine the role of immunothrombosis in COVID-19.

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 833440
• EU-Projekte: Horizon 2020 > ERC Grants > ERC Advanced Grant > ERC Grant 833440: IMMUNOTHROMBOSIS - Cross-talk between platelets and immunity - implications for host homeostasis and defense
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch