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We found that wild-type\/Wuhan variant S1 (S1WT) promoted neutrophil and macrophage recruitment, local and systemic hyperinflammation, emergency myelopoiesis, and hemorrhages. In addition, S1\u03b3 was more proinflammatory while S1\u03b4 was less proinflammatory than S1WT, and, notably, S1\u03b2 promoted delayed and long-lasting inflammation. Pharmacological inhibition of the canonical inflammasome alleviated S1-induced inflammation and emergency myelopoiesis. In contrast, genetic inhibition of angiotensin-converting enzyme 2 strengthened the proinflammatory activity of S1, and angiotensin (1-7) fully rescued S1-induced hyperinflammation and hemorrhages. These results shed light into the mechanisms orchestrating the COVID-19\u2013associated CSS and the host immune response to different SARS-CoV-2 S protein variants.<\/jats:p>","DOI":"10.1126\/sciadv.abo0732","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T17:58:17Z","timestamp":1663351097000},"source":"Crossref","is-referenced-by-count":35,"title":["Differential proinflammatory activities of Spike proteins of SARS-CoV-2 variants of concern"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-0163","authenticated-orcid":true,"given":"Sylwia D.","family":"Tyrkalska","sequence":"first","affiliation":[{"name":"Departmento de Biolog\u00eda Celular e Histolog\u00eda, Facultad de Biolog\u00eda, Universidad de Murcia, 30100 Murcia, Spain."},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB)-Arrixaca, 30120 Murcia, Spain."},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades 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