Functional immune changes are conserved in COVID-19 and trauma patients receiving intensive care

Functional immune changes are conserved in COVID-19 and trauma patients receiving intensive care | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Functional immune changes are conserved in COVID-19 and trauma patients receiving intensive care Alexander J.T. Wood, Gesa J. Albers, Willem Cornelissen, James D. Maiden, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7707950/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Critical illness states including COVID-19 and trauma induce profound immune dysregulation associated with morbidity and mortality. Direct comparison of these illnesses is crucial to identify shared pathobiological mechanisms that could guide precision therapies. This prospective cohort study undertook a comprehensive, longitudinal comparison of innate immune cell function and plasma protein expression in critically ill patients at days 1, 3, and 5 of intensive care unit admission. We enrolled 26 COVID-19, 20 trauma patients, and 18 healthy controls and analysed plasma proteins and immune cell phenotypes and responses to S. aureus coated bioparticles. An unsupervised multi-omics factor analysis (MOFA) identified shared sources of biological variation. Both patient cohorts shared profound immune alterations, including neutrophilia, decreased non-classical monocytes and dendritic cells (DCs), and a hyper-phagocytic and reactive oxygen species producing neutrophil state versus controls. Classical monocytes from patients were unable to upregulate CD11c, CD86, and SIRPα upon stimulation, and a novel phagocytosis-impaired SIRPα – CD11b – DC population was enriched from day 1. Innate immune activation profiles could segregate patients and were associated with subsequent impaired innate/adaptive crosstalk. This first direct comparison of viral sepsis (severe COVID-19) and trauma patients demonstrates many shared immune alterations between these distinct critical illnesses, which may benefit from targeted immunomodulation irrespective of clinical diagnosis. Immunology Critical Care & Emergency Medicine sepsis intensive care immune paralysis dendritic cells Full Text Additional Declarations The authors declare no competing interests. Supplementary Files 2.FICIsupplementaltablesandfigures.pdf Supplemental Tables and Figures Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7707950","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":520265393,"identity":"71831fd8-bb2a-41e6-bfd1-dc912bc7c8eb","order_by":0,"name":"Alexander J.T. Wood","email":"","orcid":"https://orcid.org/0000-0001-7819-0447","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"J.T.","lastName":"Wood","suffix":""},{"id":520265394,"identity":"bc10d9bb-48c8-4bd7-ae3e-a950d4c5a6d9","order_by":1,"name":"Gesa J. Albers","email":"","orcid":"https://orcid.org/0000-0002-8249-6956","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Gesa","middleName":"J.","lastName":"Albers","suffix":""},{"id":520265395,"identity":"0f80894b-ea21-4092-97f0-a1a02cd54336","order_by":2,"name":"Willem Cornelissen","email":"","orcid":"","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Willem","middleName":"","lastName":"Cornelissen","suffix":""},{"id":520265396,"identity":"f4c34cb3-cd37-4550-84df-f74294ad9b7b","order_by":3,"name":"James D. Maiden","email":"","orcid":"","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"James","middleName":"D.","lastName":"Maiden","suffix":""},{"id":520265397,"identity":"897f14d9-228b-49af-b15b-acb782c1881e","order_by":4,"name":"Deirdre Cuff","email":"","orcid":"","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Deirdre","middleName":"","lastName":"Cuff","suffix":""},{"id":520265398,"identity":"2a878882-b95e-4791-bfe8-bf6bd02274ad","order_by":5,"name":"Mitra Ashayeripanah","email":"","orcid":"https://orcid.org/0000-0001-8593-5996","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Mitra","middleName":"","lastName":"Ashayeripanah","suffix":""},{"id":520265399,"identity":"41afdf62-282a-4e30-8df9-5129c4f44061","order_by":6,"name":"Patrick Schriek","email":"","orcid":"https://orcid.org/0000-0002-0875-884X","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Patrick","middleName":"","lastName":"Schriek","suffix":""},{"id":520265400,"identity":"96695e7f-571b-4b31-a664-d14c244c41bd","order_by":7,"name":"Samantha J. Emery-Corbin","email":"","orcid":"https://orcid.org/0000-0003-2984-0620","institution":"Monash University","correspondingAuthor":false,"prefix":"","firstName":"Samantha","middleName":"J.","lastName":"Emery-Corbin","suffix":""},{"id":520265401,"identity":"f143a49e-e19c-4f5f-862e-61d1f7847d76","order_by":8,"name":"Nichollas E. Scott","email":"","orcid":"https://orcid.org/0000-0003-2556-8316","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Nichollas","middleName":"E.","lastName":"Scott","suffix":""},{"id":520265402,"identity":"8f7adfb4-60d3-4e80-a9c3-7098dc0abdce","order_by":9,"name":"Shihan Li","email":"","orcid":"","institution":"The Peter Doherty Institute for Infection and Immunity","correspondingAuthor":false,"prefix":"","firstName":"Shihan","middleName":"","lastName":"Li","suffix":""},{"id":520265403,"identity":"ed4cac03-e8c7-447e-8db7-b011b09c5a67","order_by":10,"name":"Jan Schröder","email":"","orcid":"https://orcid.org/0000-0001-5270-0605","institution":"The Peter Doherty Institute for Infection and Immunity","correspondingAuthor":false,"prefix":"","firstName":"Jan","middleName":"","lastName":"Schröder","suffix":""},{"id":520265404,"identity":"37a93315-5aa4-4eb4-a7f7-c305eb20b7b9","order_by":11,"name":"Adam M. Deane","email":"","orcid":"https://orcid.org/0000-0002-7620-5577","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Adam","middleName":"M.","lastName":"Deane","suffix":""},{"id":520265405,"identity":"84663169-fd54-408c-a3a9-ea51c5218136","order_by":12,"name":"Jose A. Villadangos","email":"","orcid":"https://orcid.org/0000-0001-6771-8891","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Jose","middleName":"A.","lastName":"Villadangos","suffix":""},{"id":520261005,"identity":"962d1ecd-9835-4b21-a96f-72e983ccef83","order_by":13,"name":"Laura Cook","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYBACPjB5wIaBgRlIP2wAcQhoYYNoSYNoSSRBy2EIj0gtzA8ffDhzPnE7O3fig8QdDHJ8NxIYP/Pg1cJmbDjjxu3Enc28mw0SzzAYS95IYJbGr4WHTZrnw+3EDYd5t0kktjEkbriRwECMlnMgLdt/ALXUA7Uw/yas5cYBsC0MQC0JBjcS2PDbwgzyy5lkY6CWzRKJZyQMZ5552GY5B48WfvZmYIgds5PdcP7sxg8fd9jI8x1PPnzjDR4t4BhEAhJAzNiAT8MoGAWjYBSMAiIAAAw5TU4v2OEIAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-3153-2045","institution":"University of Melbourne","correspondingAuthor":true,"prefix":"","firstName":"Laura","middleName":"","lastName":"Cook","suffix":""}],"badges":[],"createdAt":"2025-09-25 02:40:59","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7707950/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7707950/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":92381033,"identity":"7a93ef69-0670-4275-ab53-e3f4a23b5b9b","added_by":"auto","created_at":"2025-09-29 06:14:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2611842,"visible":true,"origin":"","legend":"","description":"","filename":"1.FICIPreprint.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7707950/v1_covered_7d1bb4d2-89aa-4828-a4cc-5b615f441fb3.pdf"},{"id":92380458,"identity":"581c6fc2-25ce-4e71-9db2-59e7f79e9557","added_by":"auto","created_at":"2025-09-29 06:12:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2090611,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental Tables and Figures\u003c/p\u003e","description":"","filename":"2.FICIsupplementaltablesandfigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7707950/v1/5e97c9bfe552a47a5c58ace3.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eFunctional immune changes are conserved in COVID-19 and trauma patients receiving intensive care\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"University of Melbourne","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"sepsis, intensive care, immune paralysis, dendritic cells","lastPublishedDoi":"10.21203/rs.3.rs-7707950/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7707950/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCritical illness states including COVID-19 and trauma induce profound immune dysregulation associated with morbidity and mortality. Direct comparison of these illnesses is crucial to identify shared pathobiological mechanisms that could guide precision therapies. This prospective cohort study undertook a comprehensive, longitudinal comparison of innate immune cell function and plasma protein expression in critically ill patients at days 1, 3, and 5 of intensive care unit admission. We enrolled 26 COVID-19, 20 trauma patients, and 18 healthy controls and analysed plasma proteins and immune cell phenotypes and responses to \u003cem\u003eS. aureus\u003c/em\u003e coated bioparticles. An unsupervised multi-omics factor analysis (MOFA) identified shared sources of biological variation. Both patient cohorts shared profound immune alterations, including neutrophilia, decreased non-classical monocytes and dendritic cells (DCs), and a hyper-phagocytic and reactive oxygen species producing neutrophil state versus controls. Classical monocytes from patients were unable to upregulate CD11c, CD86, and SIRPα upon stimulation, and a novel phagocytosis-impaired SIRPα\u003csup\u003e–\u003c/sup\u003eCD11b\u003csup\u003e–\u003c/sup\u003e DC population was enriched from day 1. Innate immune activation profiles could segregate patients and were associated with subsequent impaired innate/adaptive crosstalk. This first direct comparison of viral sepsis (severe COVID-19) and trauma patients demonstrates many shared immune alterations between these distinct critical illnesses, which may benefit from targeted immunomodulation irrespective of clinical diagnosis.\u003c/p\u003e","manuscriptTitle":"Functional immune changes are conserved in COVID-19 and trauma patients receiving intensive care","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-29 06:07:15","doi":"10.21203/rs.3.rs-7707950/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3106b06f-5d4c-4f38-b3bd-0bd093070f39","owner":[],"postedDate":"September 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":55475101,"name":"Immunology"},{"id":55475102,"name":"Critical Care \u0026 Emergency Medicine"}],"tags":[],"updatedAt":"2025-09-29T06:07:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-29 06:07:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7707950","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7707950","identity":"rs-7707950","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}