Plasma ACE2 species are differentially altered in COVID-19 patients
Por:
García-Ayllón MS, Moreno-Pérez O, García-Arriaza J, Ramos-Rincón JM, Cortés-Gómez MÁ, Brinkmalm G, Andrés M, León-Ramírez JM, Boix V, Gil J, Zetterberg H, Esteban M, Merino E and Saez J
Publicada:
1 ago 2021
Resumen:
Studies are needed to identify useful biomarkers to assess the severity and prognosis of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus. Here, we examine the levels of various plasma species of the SARS-CoV-2 host receptor, the angiotensin-converting enzyme 2 (ACE2), in patients at different phases of the infection. Human plasma ACE2 species were characterized by immunoprecipitation and western blotting employing antibodies against the ectodomain and the C-terminal domain, using a recombinant human ACE2 protein as control. In addition, changes in the cleaved and full-length ACE2 species were also examined in serum samples derived from humanized K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2. ACE2 immunoreactivity was present in human plasma as several molecular mass species that probably comprise truncated (70 and 75 kDa) and full-length forms (95, 100, 130, and 170 kDa). COVID-19 patients in the acute phase of infection (n = 46) had significantly decreased levels of ACE2 full-length species, while a truncated 70-kDa form was marginally higher compared with non-disease controls (n = 26). Levels of ACE2 full-length species were in the normal range in patients after a recovery period with an interval of 58-70 days (n = 29), while the 70-kDa species decreased. Levels of the truncated ACE2 species served to discriminate between individuals infected by SARS-CoV-2 and those infected with influenza A virus (n = 17). In conclusion, specific plasma ACE2 species are altered in patients with COVID-19 and these changes normalize during the recovery phase. Alterations in ACE2 species following SARS-CoV-2 infection warrant further investigation regarding their potential usefulness as biomarkers for the disease process and to asses efficacy during vaccination.
Filiaciones:
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Unidad de Investigación, Hospital General Universitario de Elche, FISABIO, Elche, Spain
Moreno-Pérez O:
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
Endocrinology and Nutrition Department, Alicante General University Hospital, Alicante, Spain
Clinical Medicine Department, Universidad Miguel Hernández, Elche, Spain
García-Arriaza J:
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
Ramos-Rincón JM:
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
Clinical Medicine Department, Universidad Miguel Hernández, Elche, Spain
Internal Medicine Department, Alicante General University Hospital, Alicante, Spain
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Unidad de Investigación, Hospital General Universitario de Elche, FISABIO, Elche, Spain
Brinkmalm G:
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Andrés M:
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
Clinical Medicine Department, Universidad Miguel Hernández, Elche, Spain
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Rheumatology Department, Alicante General University Hospital Alicante, Alicante, Spain
León-Ramírez JM:
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
Pneumology Department, Alicante General University Hospital, Alicante, Spain
Boix V:
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
Clinical Medicine Department, Universidad Miguel Hernández, Elche, Spain
Unit of Infectious Diseases, Alicante General University Hospital, Alicante, Spain
Gil J:
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
Pneumology Department, Alicante General University Hospital, Alicante, Spain
Zetterberg H:
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK
UK Dementia Research Institute, UCL, London, UK
Esteban M:
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
Merino E:
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
Unit of Infectious Diseases, Alicante General University Hospital, Alicante, Spain
Saez J:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
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