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Both, substitution of interferon and JAK\/STAT inhibition to limit cytokine storms have been proposed. However, little is known about possible abnormalities in STAT signaling in immune cells during SARS\u2010CoV\u20102 infection. We investigated downstream targets of interferon signaling, including STAT1, STAT2, pSTAT1 and 2, and IRF1, 7 and 9 by flow cytometry in 30 patients with COVID\u201019, 17 with mild, and 13 with severe infection. We report upregulation of STAT1 and IRF9 in mild and severe COVID\u201019 cases, which correlated with the IFN\u2010signature assessed by Siglec\u20101 (CD169) expression on peripheral monocytes. Interestingly, Siglec\u20101 and STAT1 in CD14+ monocytes and plasmablasts showed lower expression among severe cases compared to mild cases. Contrary to the baseline STAT1 expression, the phosphorylation of STAT1 was enhanced in severe COVID\u201019 cases, indicating a dysbalanced JAK\/STAT signaling that fails to induce transcription of interferon stimulated response elements (ISRE). This abnormality persisted after IFN\u2010\u03b1 and IFN\u2010\u03b3 stimulation of PBMCs from patients with severe COVID\u201019. Data suggest impaired STAT1 transcriptional upregulation among severely infected patients may represent a potential predictive biomarker and would allow stratification of patients for certain interferon\u2010pathway targeted treatments.<\/jats:p>","DOI":"10.1002\/eji.202149575","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T04:44:47Z","timestamp":1634877887000},"page":"138-148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Altered increase in STAT1 expression and phosphorylation in severe COVID\u201019"],"prefix":"10.1002","volume":"52","author":[{"given":"Hector","family":"Rincon\u2010Arevalo","sequence":"first","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care Charit\u00e9\u2010 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Department of Rheumatology and Clinical Immunology Charit\u00e9\u2010 Universit\u00e4tsmedizin Berlin  Berlin 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