{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:44:16Z","timestamp":1789767856398,"version":"4.0.1"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"1","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,1,6]]},"abstract":"<jats:p>\n            Spleen tyrosine kinase (SYK) is a previously unidentified  therapeutic target that inhibits neutrophil and macrophage activation in coronavirus disease 2019 (COVID-19). Fostamatinib, a SYK inhibitor, was studied in a phase 2 placebo-controlled randomized clinical trial and was associated with improvements in many secondary end points related to efficacy. Here, we used a multiomic approach to evaluate cellular and soluble immune mediator responses of patients enrolled in this trial. We demonstrated that SYK inhibition was associated with reduced neutrophil activation, increased circulation of mature neutrophils (CD10\n            <jats:sup>+<\/jats:sup>\n            CD33\n            <jats:sup>\u2212<\/jats:sup>\n            ), and decreased circulation of low-density granulocytes and polymorphonuclear myeloid-derived suppressor cells (HLA-DR\n            <jats:sup>\u2212<\/jats:sup>\n            CD33\n            <jats:sup>+<\/jats:sup>\n            CD11b\n            <jats:sup>\u2212<\/jats:sup>\n            ). SYK inhibition was also associated with normalization of transcriptional activity in circulating monocytes relative to healthy controls, an increase in frequency of circulating nonclassical and HLA-DR\n            <jats:sup>hi<\/jats:sup>\n            classical monocyte populations, and restoration of interferon responses. Together, these data suggest that SYK inhibition may mitigate proinflammatory myeloid cellular and soluble mediator responses thought to contribute to immunopathogenesis of severe COVID-19.\n          <\/jats:p>","DOI":"10.1126\/sciadv.ade8272","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T18:58:30Z","timestamp":1672858710000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":27,"title":["Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1798-4347","authenticated-orcid":true,"given":"Gustaf","family":"Wigerblad","sequence":"first","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth A.","family":"Warner","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos J.","family":"Ramos-Benitez","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD, USA."},{"name":"Postdoctoral Research Associate Training Program, National Institute of General Medical Sciences, Bethesda, MD, USA."},{"name":"Ponce Health Science University and Ponce Research Institute, Department of Basic Sciences, School of Medicine, Ponce, Puerto Rico, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lela","family":"Kardava","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mala","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Laboratory of Transplantation Immunotherapy, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7001-5265","authenticated-orcid":true,"given":"Susan","family":"Wong","sequence":"additional","affiliation":[{"name":"Laboratory of Transplantation Immunotherapy, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5660-5194","authenticated-orcid":true,"given":"Yogendra","family":"Kanthi","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Thrombosis and Inflammation, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"King","sequence":"additional","affiliation":[{"name":"Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, VA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4131-8499","authenticated-orcid":true,"given":"Oksana","family":"Shlobin","sequence":"additional","affiliation":[{"name":"Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, VA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Nathan","sequence":"additional","affiliation":[{"name":"Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, VA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cohen","sequence":"additional","affiliation":[{"name":"Adventist Healthcare Shady Grove Medical Center, Rockville, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0163-6911","authenticated-orcid":true,"given":"Susan","family":"Moir","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Childs","sequence":"additional","affiliation":[{"name":"Laboratory of Transplantation Immunotherapy, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA."},{"name":"United States Public Health Service Commissioned Corps, Rockville, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-0815","authenticated-orcid":true,"given":"Mariana J.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and 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