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COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system.
Rysz, Susanne; Al-Saadi, Jonathan; Sjöström, Anna; Farm, Maria; Campoccia Jalde, Francesca; Plattén, Michael; Eriksson, Helen; Klein, Margareta; Vargas-Paris, Roberto; Nyrén, Sven; Abdula, Goran; Ouellette, Russell; Granberg, Tobias; Jonsson Fagerlund, Malin; Lundberg, Johan.
  • Rysz S; Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  • Al-Saadi J; Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
  • Sjöström A; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Farm M; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Campoccia Jalde F; Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
  • Plattén M; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Eriksson H; Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
  • Klein M; Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
  • Vargas-Paris R; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Nyrén S; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Abdula G; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
  • Ouellette R; Department of Sociology, Stockholm University Demography Unit, Stockholm University, Stockholm, Sweden.
  • Granberg T; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Jonsson Fagerlund M; Department of Radiology Huddinge, Karolinska University Hospital, Stockholm, Sweden.
  • Lundberg J; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Nat Commun ; 12(1): 2417, 2021 04 23.
Artículo en Inglés | MEDLINE | ID: covidwho-1203428
ABSTRACT
SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.
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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Sistema Renina-Angiotensina / SARS-CoV-2 / COVID-19 / Pulmón Tipo de estudio: Estudio de cohorte / Estudio observacional / Estudio pronóstico Límite: Animales / Femenino / Humanos Idioma: Inglés Revista: Nat Commun Asunto de la revista: Biologia / Ciencia Año: 2021 Tipo del documento: Artículo País de afiliación: S41467-021-22713-z

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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Sistema Renina-Angiotensina / SARS-CoV-2 / COVID-19 / Pulmón Tipo de estudio: Estudio de cohorte / Estudio observacional / Estudio pronóstico Límite: Animales / Femenino / Humanos Idioma: Inglés Revista: Nat Commun Asunto de la revista: Biologia / Ciencia Año: 2021 Tipo del documento: Artículo País de afiliación: S41467-021-22713-z