{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T20:59:48Z","timestamp":1773176388793,"version":"3.50.1"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2016YFC0901700"],"award-info":[{"award-number":["2016YFC0901700"]}]},{"name":"Strategic Priority Research Program of Chinese Academy of Sciences","award":["XDB38030200"],"award-info":[{"award-number":["XDB38030200"]}]},{"name":"National High Technology Program of China","award":["2015AA020108"],"award-info":[{"award-number":["2015AA020108"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>For coronavirus disease 2019 (COVID-19), a pandemic disease characterized by strong immune dysregulation in severe patients, convenient and efficient monitoring of the host immune response is critical. Human hosts respond to viral and bacterial infections in different ways, the former is characterized by the activation of interferon stimulated genes (ISGs) such as <jats:italic>IFI27<\/jats:italic>, while the latter is characterized by the activation of anti-bacterial associated genes (ABGs) such as <jats:italic>S100A12<\/jats:italic>. This two-tiered innate immune response has not been examined in COVID-19. In this study, the activation patterns of this two-tiered innate immune response represented by <jats:italic>IFI27<\/jats:italic> and <jats:italic>S100A12<\/jats:italic> were explored based on 1421 samples from 17 transcriptome datasets derived from the blood of COVID-19 patients and relevant controls. It was found that <jats:italic>IFI27<\/jats:italic> activation occurred in most of the symptomatic patients and displayed no correlation with disease severity, while <jats:italic>S100A12<\/jats:italic> activation was more restricted to patients under severe and critical conditions with a stepwise activation pattern. In addition, most of the <jats:italic>S100A12<\/jats:italic> activation was accompanied by <jats:italic>IFI27<\/jats:italic> activation. Furthermore, the activation of <jats:italic>IFI27<\/jats:italic> was most pronounced within the first week of symptom onset, but generally waned after 2\u20133 weeks. On the other hand, the activation of <jats:italic>S100A12<\/jats:italic> displayed no apparent correlation with disease duration and could last for several months in certain patients. These features of the two-tiered innate immune response can further our understanding on the disease mechanism of COVID-19 and may have implications to the clinical triage. Development of a convenient two-gene protocol for the routine serial monitoring of this two-tiered immune response will be a valuable addition to the existing laboratory tests.<\/jats:p>","DOI":"10.1371\/journal.pone.0280392","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T04:08:44Z","timestamp":1674014924000},"page":"e0280392","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["A two-gene marker for the two-tiered innate immune response in COVID-19 patients"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0496-0386","authenticated-orcid":true,"given":"Hongxing","family":"Lei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"pone.0280392.ref001","doi-asserted-by":"crossref","first-page":"o867","DOI":"10.1136\/bmj.o867","article-title":"The benefits of large scale covid-19 vaccination","volume":"377","author":"C. Dye","year":"2022","journal-title":"Bmj"},{"key":"pone.0280392.ref002","first-page":"o1045","article-title":"A living WHO guideline on drugs for covid-19","volume":"377","year":"2022","journal-title":"Bmj"},{"key":"pone.0280392.ref003","doi-asserted-by":"crossref","first-page":"857573","DOI":"10.3389\/fimmu.2022.857573","article-title":"Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19","volume":"13","author":"D Battaglini","year":"2022","journal-title":"Frontiers in immunology"},{"key":"pone.0280392.ref004","doi-asserted-by":"crossref","first-page":"912336","DOI":"10.3389\/fimmu.2022.912336","article-title":"Hallmarks of Severe COVID-19 Pathogenesis: A Pas de Deux Between Viral and Host Factors","volume":"13","author":"R Rovito","year":"2022","journal-title":"Frontiers in immunology"},{"key":"pone.0280392.ref005","doi-asserted-by":"crossref","first-page":"2571912","DOI":"10.1155\/2021\/2571912","article-title":"Value of the Neutrophil-Lymphocyte Ratio in Predicting COVID-19 Severity: A Meta-analysis","volume":"2021","author":"Y Wang","year":"2021","journal-title":"Dis Markers"},{"issue":"12","key":"pone.0280392.ref006","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1111\/jth.15534","article-title":"Platelets contribute to disease severity in COVID-19","volume":"19","author":"TJ Barrett","year":"2021","journal-title":"Journal of thrombosis and haemostasis: JTH"},{"issue":"1","key":"pone.0280392.ref007","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12879-021-07016-4","article-title":"Monocyte distribution width as a novel sepsis indicator in COVID-19 patients","volume":"22","author":"L Alsuwaidi","year":"2022","journal-title":"BMC infectious diseases"},{"issue":"1","key":"pone.0280392.ref008","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1080\/07853890.2021.1968484","article-title":"Evaluating red blood cell distribution width from community blood tests as a predictor of hospitalization and mortality in adults with SARS-CoV-2: a cohort study","volume":"53","author":"T Banon","year":"2021","journal-title":"Annals of medicine"},{"key":"pone.0280392.ref009","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.ajem.2020.11.011","article-title":"Clinical value of procalcitonin in critically ill patients infected by SARS-CoV-2","volume":"46","author":"P Garrido","year":"2021","journal-title":"The American journal of emergency medicine"},{"key":"pone.0280392.ref010","doi-asserted-by":"crossref","first-page":"e3547","DOI":"10.6061\/clinics\/2021\/e3547","article-title":"Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study","volume":"76","author":"FAR Goncalves","year":"2021","journal-title":"Clinics"},{"issue":"8","key":"pone.0280392.ref011","doi-asserted-by":"crossref","first-page":"e0256744","DOI":"10.1371\/journal.pone.0256744","article-title":"D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19","volume":"16","author":"A Poudel","year":"2021","journal-title":"PloS one"},{"issue":"5","key":"pone.0280392.ref012","doi-asserted-by":"crossref","first-page":"e0269005","DOI":"10.1371\/journal.pone.0269005","article-title":"Clinical utility of inflammatory biomarkers in COVID-19 in direct comparison to other respiratory infections-A prospective cohort study","volume":"17","author":"M Lampart","year":"2022","journal-title":"PloS one"},{"issue":"3","key":"pone.0280392.ref013","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jemermed.2021.03.012","article-title":"Soluble Urokinase Plasminogen Activator Receptor as a Decision Marker for Early Discharge of Patients with COVID-19 Symptoms in the Emergency Department","volume":"61","author":"MA Stauning","year":"2021","journal-title":"The Journal of emergency medicine"},{"issue":"1","key":"pone.0280392.ref014","doi-asserted-by":"crossref","first-page":"15872","DOI":"10.1038\/s41598-021-95431-7","article-title":"Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19","volume":"11","author":"C Su","year":"2021","journal-title":"Sci Rep"},{"issue":"6","key":"pone.0280392.ref015","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2217\/bmm-2021-0681","article-title":"Organ function biomarker abnormalities, associated factors and disease outcome among hospitalized patients with COVID-19","volume":"16","author":"S Araya","year":"2022","journal-title":"Biomarkers in medicine"},{"issue":"1","key":"pone.0280392.ref016","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1186\/s12879-021-06572-z","article-title":"Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study","volume":"21","author":"QL Zeng","year":"2021","journal-title":"BMC infectious diseases"},{"issue":"6","key":"pone.0280392.ref017","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/s41591-022-01837-9","article-title":"A multisystem, cardio-renal investigation of post-COVID-19 illness","volume":"28","author":"AJ Morrow","year":"2022","journal-title":"Nature medicine"},{"key":"pone.0280392.ref018","doi-asserted-by":"crossref","first-page":"e069881","DOI":"10.1136\/bmj-2021-069881","article-title":"Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis","volume":"378","author":"VMT de Jong","year":"2022","journal-title":"Bmj"},{"issue":"4","key":"pone.0280392.ref019","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s11739-021-02924-4","article-title":"Clusters of inflammation in COVID-19: descriptive analysis and prognosis on more than 15,000 patients from the Spanish SEMI-COVID-19 Registry","volume":"17","author":"M Rubio-Rivas","year":"2022","journal-title":"Internal and emergency medicine"},{"issue":"1","key":"pone.0280392.ref020","doi-asserted-by":"crossref","first-page":"21888","DOI":"10.1038\/s41598-021-01462-5","article-title":"D-dimer, disease severity, and deaths (3D-study) in patients with COVID-19: a systematic review and meta-analysis of 100 studies","volume":"11","author":"SR Varikasuvu","year":"2021","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0280392.ref021","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1186\/s12879-022-07383-6","article-title":"Predictors of critical care, mechanical ventilation, and mortality among hospitalized patients with COVID-19 in an electronic health record database","volume":"22","author":"AK Chomistek","year":"2022","journal-title":"BMC infectious diseases"},{"issue":"1","key":"pone.0280392.ref022","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1186\/s12879-022-07520-1","article-title":"Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans","volume":"22","author":"H Ashktorab","year":"2022","journal-title":"BMC infectious diseases"},{"issue":"7895","key":"pone.0280392.ref023","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41586-021-04280-x","article-title":"Signature of long-lived memory CD8(+) T cells in acute SARS-CoV-2 infection","volume":"602","author":"S Adamo","year":"2022","journal-title":"Nature"},{"issue":"1","key":"pone.0280392.ref024","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41467-021-27716-4","article-title":"Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19","volume":"13","author":"A Unterman","year":"2022","journal-title":"Nature communications"},{"issue":"62","key":"pone.0280392.ref025","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abg5021","article-title":"Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients","volume":"6","author":"S Notarbartolo","year":"2021","journal-title":"Science immunology"},{"issue":"7","key":"pone.0280392.ref026","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.immuni.2021.05.002","article-title":"Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia","volume":"54","author":"S Kreutmair","year":"2021","journal-title":"Immunity"},{"issue":"1","key":"pone.0280392.ref027","doi-asserted-by":"crossref","first-page":"20638","DOI":"10.1038\/s41598-021-98253-9","article-title":"Identification of serum prognostic biomarkers of severe COVID-19 using a quantitative proteomic approach","volume":"11","author":"Y Kimura","year":"2021","journal-title":"Sci Rep"},{"issue":"10","key":"pone.0280392.ref028","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.1021\/acs.jproteome.1c00475","article-title":"Discovery Proteomics for COVID-19: Where We Are Now","volume":"20","author":"A McArdle","year":"2021","journal-title":"Journal of proteome research"},{"issue":"1","key":"pone.0280392.ref029","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41392-022-00976-2","article-title":"Novel potential metabolic biomarker panel for early detection of severe COVID-19 using full-spectrum metabolome and whole-transcriptome analyses","volume":"7","author":"ZB Li","year":"2022","journal-title":"Signal transduction and targeted therapy"},{"issue":"8","key":"pone.0280392.ref030","doi-asserted-by":"crossref","first-page":"100369","DOI":"10.1016\/j.xcrm.2021.100369","article-title":"Longitudinal metabolomics of human plasma reveals prognostic markers of COVID-19 disease severity","volume":"2","author":"M Sindelar","year":"2021","journal-title":"Cell reports Medicine"},{"issue":"8","key":"pone.0280392.ref031","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1021\/acs.jproteome.1c00458","article-title":"Integrative Modeling of Plasma Metabolic and Lipoprotein Biomarkers of SARS-CoV-2 Infection in Spanish and Australian COVID-19 Patient Cohorts","volume":"20","author":"R Masuda","year":"2021","journal-title":"Journal of proteome research"},{"issue":"1","key":"pone.0280392.ref032","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41392-021-00822-x","article-title":"COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors","volume":"6","author":"X He","year":"2021","journal-title":"Signal transduction and targeted therapy"},{"issue":"1","key":"pone.0280392.ref033","doi-asserted-by":"crossref","first-page":"22958","DOI":"10.1038\/s41598-021-02489-4","article-title":"Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome","volume":"11","author":"KI Masood","year":"2021","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0280392.ref034","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1080\/22221751.2022.2038021","article-title":"Plasma miRNA profile at COVID-19 onset predicts severity status and mortality","volume":"11","author":"A Fernandez-Pato","year":"2022","journal-title":"Emerging microbes & infections"},{"issue":"2","key":"pone.0280392.ref035","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1101\/gr.276175.121","article-title":"Plasma cell-free RNA characteristics in COVID-19 patients","volume":"32","author":"Y Wang","year":"2022","journal-title":"Genome research"},{"key":"pone.0280392.ref036","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: a complex web of host defenses","volume":"32","author":"WM Schneider","year":"2014","journal-title":"Annual review of immunology"},{"issue":"8","key":"pone.0280392.ref037","doi-asserted-by":"crossref","first-page":"e0182294","DOI":"10.1371\/journal.pone.0182294","article-title":"The frontline of immune response in peripheral blood","volume":"12","author":"F Song","year":"2017","journal-title":"PloS one"},{"key":"pone.0280392.ref038","article-title":"A host-based two-gene model for the identification of bacterial infection in general clinical settings","author":"H Lei","year":"2021","journal-title":"International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases"},{"issue":"6","key":"pone.0280392.ref039","article-title":"A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infection","volume":"49","author":"BM Tang","year":"2017","journal-title":"The European respiratory journal"},{"issue":"8","key":"pone.0280392.ref040","doi-asserted-by":"crossref","first-page":"e507","DOI":"10.1016\/S2589-7500(21)00102-3","article-title":"A two-transcript biomarker of host classifier genes for discrimination of bacterial from viral infection in acute febrile illness: a multicentre discovery and validation study","volume":"3","author":"N Xu","year":"2021","journal-title":"The Lancet Digital health"},{"issue":"8","key":"pone.0280392.ref041","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1001\/jama.2016.11236","article-title":"Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children","volume":"316","author":"JA Herberg","year":"2016","journal-title":"JAMA"},{"issue":"1","key":"pone.0280392.ref042","doi-asserted-by":"crossref","first-page":"101947","DOI":"10.1016\/j.isci.2020.101947","article-title":"Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections","volume":"24","author":"SA Thair","year":"2021","journal-title":"iScience"},{"issue":"7","key":"pone.0280392.ref043","doi-asserted-by":"crossref","first-page":"102711","DOI":"10.1016\/j.isci.2021.102711","article-title":"CD177, a specific marker of neutrophil activation, is associated with coronavirus disease 2019 severity and death","volume":"24","author":"Y Levy","year":"2021","journal-title":"iScience"},{"key":"pone.0280392.ref044","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.65508","article-title":"Seroconversion stages COVID19 into distinct pathophysiological states","volume":"10","author":"MD Galbraith","year":"2021","journal-title":"eLife"},{"issue":"628","key":"pone.0280392.ref045","doi-asserted-by":"crossref","first-page":"eabj7521","DOI":"10.1126\/scitranslmed.abj7521","article-title":"Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort","volume":"14","author":"R Carapito","year":"2022","journal-title":"Science translational medicine"},{"issue":"5","key":"pone.0280392.ref046","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.cell.2022.01.012","article-title":"A blood atlas of COVID-19 defines hallmarks of disease severity and specificity","volume":"185","author":"Consortium CO-M-oBA","year":"2022","journal-title":"Cell"},{"issue":"1","key":"pone.0280392.ref047","doi-asserted-by":"crossref","first-page":"e0261679","DOI":"10.1371\/journal.pone.0261679","article-title":"RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections","volume":"17","author":"R Wargodsky","year":"2022","journal-title":"PloS one"},{"issue":"6","key":"pone.0280392.ref048","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.immuni.2020.11.017","article-title":"Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19","volume":"53","author":"JP Bernardes","year":"2020","journal-title":"Immunity"},{"issue":"1","key":"pone.0280392.ref049","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s41467-021-21289-y","article-title":"Dysregulated transcriptional responses to SARS-CoV-2 in the periphery","volume":"12","author":"MT McClain","year":"2021","journal-title":"Nature communications"},{"issue":"1","key":"pone.0280392.ref050","doi-asserted-by":"crossref","first-page":"109773","DOI":"10.1016\/j.celrep.2021.109773","article-title":"Robust innate responses to SARS-CoV-2 in children resolve faster than in adults without compromising adaptive immunity","volume":"37","author":"M Vono","year":"2021","journal-title":"Cell reports"},{"key":"pone.0280392.ref051","article-title":"Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19","author":"Z Hu","year":"2022","journal-title":"Research square"},{"issue":"1","key":"pone.0280392.ref052","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12916-021-02228-6","article-title":"Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection","volume":"20","author":"FJ Ryan","year":"2022","journal-title":"BMC Med"},{"issue":"1","key":"pone.0280392.ref053","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s40635-020-00361-9","article-title":"Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation","volume":"8","author":"SE Gill","year":"2020","journal-title":"Intensive care medicine experimental"},{"issue":"1","key":"pone.0280392.ref054","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cels.2020.10.003","article-title":"Large-Scale Multi-omic Analysis of COVID-19 Severity","volume":"12","author":"KA Overmyer","year":"2021","journal-title":"Cell systems"},{"issue":"6508","key":"pone.0280392.ref055","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1126\/science.abc6261","article-title":"Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans","volume":"369","author":"PS Arunachalam","year":"2020","journal-title":"Science"},{"key":"pone.0280392.ref056","doi-asserted-by":"crossref","first-page":"716075","DOI":"10.3389\/fimmu.2021.716075","article-title":"Transcriptome Analysis of Peripheral Blood Mononuclear Cells Reveals Distinct Immune Response in Asymptomatic and Re-Detectable Positive COVID-19 Patients","volume":"12","author":"J Zhang","year":"2021","journal-title":"Frontiers in immunology"},{"issue":"6","key":"pone.0280392.ref057","doi-asserted-by":"crossref","first-page":"e1004869","DOI":"10.1371\/journal.ppat.1004869","article-title":"Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections\u2014A Prospective Cohort Study","volume":"11","author":"Y Zhai","year":"2015","journal-title":"PLoS pathogens"},{"issue":"427","key":"pone.0280392.ref058","first-page":"1","article-title":"Mortality in the United States, 2020","author":"SL Murphy","year":"2021","journal-title":"NCHS data brief"},{"issue":"12","key":"pone.0280392.ref059","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1515\/cclm-2021-0694","article-title":"Daily monitoring of viral load measured as SARS-CoV-2 antigen and RNA in blood, IL-6, CRP and complement C3d predicts outcome in patients hospitalized with COVID-19","volume":"59","author":"CL Brasen","year":"2021","journal-title":"Clinical chemistry and laboratory medicine"},{"issue":"1","key":"pone.0280392.ref060","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12879-022-07144-5","article-title":"High procalcitonin levels associated with increased intensive care unit admission and mortality in patients with a COVID-19 infection in the emergency department","volume":"22","author":"K Tong-Minh","year":"2022","journal-title":"BMC infectious diseases"},{"key":"pone.0280392.ref061","doi-asserted-by":"crossref","first-page":"108435","DOI":"10.1016\/j.intimp.2021.108435","article-title":"Prognostic role of Interleukin-6\/lymphocytes ratio in SARS-CoV2 related pneumonia","volume":"103","author":"L Masotti","year":"2022","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"pone.0280392.ref062","doi-asserted-by":"crossref","first-page":"12174","DOI":"10.1038\/s41598-021-91754-7","article-title":"A single transcript for the prognosis of disease severity in COVID-19 patients","volume":"11","author":"H. Lei","year":"2021","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0280392.ref063","doi-asserted-by":"crossref","first-page":"14471","DOI":"10.1038\/s41598-021-93950-x","article-title":"Longitudinal monitoring of laboratory markers characterizes hospitalized and ambulatory COVID-19 patients","volume":"11","author":"TP Velavan","year":"2021","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0280392.ref064","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1007\/s11739-020-02560-4","article-title":"Baseline characteristics and changes of biomarkers in disease course predict prognosis of patients with COVID-19","volume":"16","author":"T Li","year":"2021","journal-title":"Internal and emergency medicine"},{"key":"pone.0280392.ref065","doi-asserted-by":"crossref","first-page":"n1648","DOI":"10.1136\/bmj.n1648","article-title":"Long covid-mechanisms, risk factors, and management","volume":"374","author":"H Crook","year":"2021","journal-title":"Bmj"},{"key":"pone.0280392.ref066","article-title":"Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients","author":"R Carbonell","year":"2022","journal-title":"The Journal of infection"},{"issue":"4","key":"pone.0280392.ref067","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.3233\/JAD-190666","article-title":"Evaluation of Peripheral Immune Dysregulation in Alzheimer\u2019s Disease and Vascular Dementia","volume":"71","author":"Z Guo","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"pone.0280392.ref068","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ijid.2020.11.205","article-title":"Single-cell RNA-Seq revealed profound immune alteration in the peripheral blood of patients with bacterial infection","volume":"103","author":"H Lei","year":"2021","journal-title":"International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0280392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T04:09:51Z","timestamp":1674014991000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0280392"}},"subtitle":[],"editor":[{"given":"Benjamin M.","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,17]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0280392","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,17]]}}}