Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19

{ 'indexed': {'date-parts': [[2023, 12, 2]], 'date-time': '2023-12-02T00:52:36Z', 'timestamp': 1701478356998}, 'reference-count': 359, 'publisher': 'MDPI AG', 'issue': '23', 'license': [ { 'start': { 'date-parts': [[2023, 12, 1]], 'date-time': '2023-12-01T00:00:00Z', 'timestamp': 1701388800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Consistent with well-established biochemical properties of coronaviruses, sialylated ' 'glycan attachments between SARS-CoV-2 spike protein (SP) and host cells are key to the ' 'virus’s pathology. SARS-CoV-2 SP attaches to and aggregates red blood cells (RBCs), as shown ' 'in many pre-clinical and clinical studies, causing pulmonary and extrapulmonary microthrombi ' 'and hypoxia in severe COVID-19 patients. SARS-CoV-2 SP attachments to the heavily sialylated ' 'surfaces of platelets (which, like RBCs, have no ACE2) and endothelial cells (having minimal ' 'ACE2) compound this vascular damage. Notably, experimentally induced RBC aggregation in vivo ' 'causes the same key morbidities as for severe COVID-19, including microvascular occlusion, ' 'blood clots, hypoxia and myocarditis. Key risk factors for COVID-19 morbidity, including ' 'older age, diabetes and obesity, are all characterized by markedly increased propensity to ' 'RBC clumping. For mammalian species, the degree of clinical susceptibility to COVID-19 ' 'correlates to RBC aggregability with p = 0.033. Notably, of the five human betacoronaviruses, ' 'the two common cold strains express an enzyme that releases glycan attachments, while the ' 'deadly SARS, SARS-CoV-2 and MERS do not, although viral loads for COVID-19 and the two common ' 'cold infections are similar. These biochemical insights also explain the previously puzzling ' 'clinical efficacy of certain generics against COVID-19 and may support the development of ' 'future therapeutic strategies for COVID-19 and long COVID patients.</jats:p>', 'DOI': '10.3390/ijms242317039', 'type': 'journal-article', 'created': {'date-parts': [[2023, 12, 1]], 'date-time': '2023-12-01T13:36:59Z', 'timestamp': 1701437819000}, 'page': '17039', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern ' 'the Severe Morbidities of COVID-19', 'prefix': '10.3390', 'volume': '24', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-6841-7054', 'authenticated-orcid': False, 'given': 'David E.', 'family': 'Scheim', 'sequence': 'first', 'affiliation': [ { 'name': 'US Public Health Service, Commissioned Corps, Inactive Reserve, ' 'Blacksburg, VA 24060, USA'}]}, { 'ORCID': 'http://orcid.org/0000-0002-6171-5427', 'authenticated-orcid': False, 'given': 'Paola', 'family': 'Vottero', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Biomedical Engineering, University of Alberta, ' 'Edmonton, AB T6G 1Z2, Canada'}]}, { 'ORCID': 'http://orcid.org/0000-0003-4724-9738', 'authenticated-orcid': False, 'given': 'Alessandro D.', 'family': 'Santin', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Obstetrics, Gynecology & Reproductive Sciences, ' 'Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520, ' 'USA'}]}, { 'given': 'Allen G.', 'family': 'Hirsh', 'sequence': 'additional', 'affiliation': [{'name': 'CryoBioPhysica Inc., Chevy Chase, MD 20815, USA'}]}], 'member': '1968', 'published-online': {'date-parts': [[2023, 12, 1]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '210138', 'DOI': '10.1183/16000617.0138-2021', 'article-title': 'COVID-19 pneumonia: Pathophysiology and management', 'volume': '30', 'author': 'Gattinoni', 'year': '2021', 'journal-title': 'Eur. Respir. Rev.'}, { 'key': 'ref_2', 'doi-asserted-by': 'crossref', 'first-page': '1471', 'DOI': '10.1016/j.chest.2021.06.016', 'article-title': 'Pulmonary Thrombosis and Thromboembolism in COVID-19', 'volume': '160', 'author': 'Poor', 'year': '2021', 'journal-title': 'Chest'}, { 'key': 'ref_3', 'doi-asserted-by': 'crossref', 'unstructured': 'Selickman, J., Vrettou, C.S., Mentzelopoulos, S.D., and Marini, J.J. ' '(2022). 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