An immune-based biomarker signature is associated with mortality in COVID-19 patients.
Michael S. Abers,Ottavia M. Delmonte,Emily Ricotta,Jonathan Fintzi,Danielle Fink,Adriana Almeida de Jesus,Kol A. Zarember,Sara Alehashemi,Vasileios Oikonomou,Jigar V. Desai,Scott W. Canna,Bita Shakoory,Kerry Dobbs,Luisa Imberti,Alessandra Sottini,Eugenia Quiros-Roldan,Francesco Castelli,Camillo Rossi,Duilio Brugnoni,Andrea Biondi,Laura Rachele Bettini,Mariella D'Angiò,Paolo Bonfanti,Riccardo Castagnoli,Daniela Montagna,Amelia Licari,Gian Luigi Marseglia,Emily F. Gliniewicz,Elana Shaw,Dana Kahle,Andre Rastegar,Michael Stack,Katherine Myint-Hpu,Susan L Levinson,Mark J. DiNubile,Daniel W. Chertow,Peter D. Burbelo,Jeffrey I. Cohen,Katherine R. Calvo,John S. Tsang,Helen C. Su,John I. Gallin,Douglas B. Kuhns,Raphaela Goldbach-Mansky,Michail S. Lionakis,Luigi D. Notarangelo +45 more
TLDR
Levels of 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.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.read more
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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
Fei Zhou,Ting Yu,Ronghui Du,Guohui Fan,Ying Liu,Zhibo Liu,Jie Xiang,Yeming Wang,Bin Song,Xiaoying Gu,Xiaoying Gu,Lulu Guan,Yuan Wei,Li Hui,Xudong Wu,Jiuyang Xu,Shengjin Tu,Yi Zhang,Hua Chen,Bin Cao +19 more
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
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Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19.
Can Liu,Can Liu,Andrew J. Martins,William W. Lau,Nicholas Rachmaninoff,Nicholas Rachmaninoff,Jinguo Chen,Luisa Imberti,Darius Mostaghimi,Danielle Fink,Peter D. Burbelo,Kerry Dobbs,Ottavia M. Delmonte,Neha Bansal,Laura Failla,Alessandra Sottini,Eugenia Quiros-Roldan,Kyu Lee Han,Brian Sellers,Foo Cheung,Rachel Sparks,Tae Wook Chun,Susan Moir,Michail S. Lionakis,Michael S. Abers,Richard Apps,Marita Bosticardo,Pedro Milanez-Almeida,Matthew P. Mulé,Elana Shaw,Yu Zhang,Francesco Castelli,Maria Lorenza Muiesan,Gabriele Tomasoni,Francesco Scolari,Alessandra Tucci,Camillo Rossi,Helen C. Su,Douglas B. Kuhns,Jeffrey I. Cohen,Luigi D. Notarangelo,John S. Tsang +41 more
TL;DR: In this article, the authors longitudinally assessed circulating proteins as well as 188 surface protein markers, transcriptome, and T-cell receptor sequence simultaneously in single peripheral immune cells from COVID-19 patients.
Journal ArticleDOI
Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19
Keith Sacco,Riccardo Castagnoli,Svetlana Vakkilainen,Chien-Liang Liu,Ottavia M. Delmonte,Cihan Oguz,Ian Kaplan,Sara Alehashemi,Peter D. Burbelo,Farzana Bhuyan,Adriana Almeida de Jesus,Kerry Dobbs,Lindsey B. Rosen,A. Chen,Elana Shaw,Mikko S. Vakkilainen,Francesca Pala,Justin B. Lack,Yu Zhang,Danielle Fink,Vasilis Oikonomou,Andrew L. Snow,Clifton L. Dalgard,Jinguo Chen,Brian Sellers,Gina A. Montealegre Sanchez,Karyl S. Barron,Emma Rey-Jurado,Cecilia Vial,M. Cecilia Poli,Amelia Licari,Daniela Montagna,Gian Luigi Marseglia,Francesco Licciardi,Ugo Ramenghi,Valentina Discepolo,Andrea Lo Vecchio,Alfredo Guarino,Eli M. Eisenstein,Luisa Imberti,Alessandra Sottini,Andrea Biondi,Sayonara Pérez Mato,Dana Gerstbacher,M. Truong,Michael Stack,Mary Magliocco,Marita Bosticardo,Tomoki Kawai,Jeffrey Danielson,Tyler W. Hulett,Manor Askenazi,Shaohui Hu,Jeffrey I. Cohen,Helen C. Su,Douglas B. Kuhns,Michail S. Lionakis,Thomas M. Snyder,Steven M. Holland,Raphaela Goldbach-Mansky,John S. Tsang,Luigi D. Notarangelo +61 more
TL;DR: In this article , a longitudinal multi-institutional study was conducted to identify distinct immunopathological signatures in COVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.
Journal ArticleDOI
Circulating Calprotectin as a Biomarker of COVID-19 Severity.
TL;DR: In this article, Calprotectin levels were reported to be associated with poor clinical outcomes such as significantly reduced survival time, especially in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Journal ArticleDOI
Lessons learned: new insights on the role of cytokines in COVID-19.
Maja Buszko,Aleksandra Nita-Lazar,Jung-Hyun Park,Pamela L. Schwartzberg,Daniela Verthelyi,Howard A. Young,Amy S. Rosenberg +6 more
TL;DR: In the midst of resurging COVID-19 cases, the second NIH/FDA virtual COVID19 and Cytokines symposium was held on 1 December 2020, focusing on longitudinal studies of COVID 19 immunity, including long-term consequences, potential associations with autoimmunity and the multisystem inflammatory syndrome in children (MIS-C) as discussed by the authors.
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