{"doi":"10.1172/jci.insight.144455","title":"An immune-based biomarker signature is associated with mortality in COVID-19 patients","abstract":"Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.","journal":"JCI Insight","year":2020,"id":48652,"datarank":0.887834078140972,"base_score":5.918893854273146,"endowment":5.918893854273146,"self_citation_contribution":0.887834078140972,"citation_network_contribution":0.0,"self_endowment_contribution":0.887834078140972,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":371,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104168,"name":"Ottavia M. 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Desai","orcid":"0000-0002-8823-0796","position":9,"is_corresponding":false},{"id":231234,"name":"Scott Canna","orcid":"0000-0003-3837-5337","position":10,"is_corresponding":false},{"id":231235,"name":"Bita Shakoory","orcid":"0000-0003-4615-370X","position":11,"is_corresponding":false},{"id":104155,"name":"Kerry Dobbs","orcid":"0000-0002-3432-3137","position":12,"is_corresponding":false},{"id":104205,"name":"Luisa Imberti","orcid":"0000-0002-2075-8391","position":13,"is_corresponding":false},{"id":231236,"name":"Alessandra Sottini","orcid":"0000-0001-5723-9619","position":14,"is_corresponding":false},{"id":104208,"name":"Eugenia Quirós-Roldán","orcid":"0000-0003-1452-9100","position":15,"is_corresponding":false},{"id":231237,"name":"Francesco Castelli","orcid":"0000-0001-9161-7804","position":16,"is_corresponding":false},{"id":231238,"name":"Camillo Rossi","orcid":"0000-0001-9271-813X","position":17,"is_corresponding":false},{"id":231239,"name":"Duilio Brugnoni","orcid":"0000-0001-9420-9961","position":18,"is_corresponding":false},{"id":104195,"name":"Andrea Biondi","orcid":"0000-0002-6757-6173","position":19,"is_corresponding":false},{"id":104196,"name":"Laura Rachele Bettini","orcid":"0000-0002-0280-1704","position":20,"is_corresponding":false},{"id":104197,"name":"Mariella D’Angiò","orcid":"0000-0001-7889-8576","position":21,"is_corresponding":false},{"id":104198,"name":"Paolo Bonfanti","orcid":"0000-0001-7289-8823","position":22,"is_corresponding":false},{"id":104210,"name":"Riccardo Castagnoli","orcid":"0000-0003-0029-9383","position":23,"is_corresponding":false},{"id":104211,"name":"Daniela Montagna","orcid":"0000-0002-1533-579X","position":24,"is_corresponding":false},{"id":104212,"name":"Amelia Licari","orcid":"0000-0002-1773-6482","position":25,"is_corresponding":false},{"id":234137,"name":"Emily F. 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