Sepsis in patients who are immunocompromised: diagnostic challenges and future therapies

Stefanie Deinhardt-Emmer¹, Benjamin G Chousterman², Joerg C Schefold³, Stefanie B Flohé⁴, Tomasz Skirecki⁵, Matthijs Kox⁶, Martin S Winkler⁷, Andrea Cossarizza⁸, W Joost Wiersinga⁹, Tom van der Poll⁹, Markus A Weigand¹⁰, Sara Cajander¹¹, Evangelos J Giamarellos-Bourboulis¹², Gunnar Lachmann¹³, Massimo Girardis¹⁴, Brendon P Scicluna¹⁵, Ricard Ferrer¹⁶, Didier Payen¹⁷, Sebastian Weis¹⁸, Antoni Torres¹⁹, Jesús F Bermejo-Martín²⁰, Marcin F Osuchowski²¹, Ignacio Rubio²², Hjalmar R Bouma²³

Affiliations

¹ Institute of Medical Microbiology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany.
² Department of Anesthesia and Critical Care, Lariboisière Hospital, APHP, Paris, France; Université Paris Cité, Inserm UMRS 942 Mascot, Paris, France.
³ Department of Intensive Care Medicine, Inselspital, University of Bern, Bern University Hospital, Bern, Switzerland.
⁴ Department of Trauma, Hand, and Reconstructive Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁵ Department of Translational Immunology and Experimental Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland.
⁶ Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
⁷ Department of Anaesthesiology, University Medical Center Göttingen, Göttingen, Germany.
⁸ Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
⁹ Center for Experimental and Molecular Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Department of Medicine, Division of Infectious Diseases, Amsterdam University Medical Center, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, Netherlands.
¹⁰ Department of Anesthesiology, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
¹¹ Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
¹² 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece; Hellenic Institute for the Study of Sepsis, Athens, Greece.
¹³ Department of Anesthesiology and Intensive Care Medicine Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁴ Department of Anesthesiology and Intensive Care Medicine, University Hospital of Modena, University of Modena and Reggio Emilia, Modena, Italy.
¹⁵ Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei hospital, University of Malta, Malta; Centre for Molecular Medicine and Biobanking, Biomedical Sciences, University of Malta, Malta.
¹⁶ Department of Intensive Care Medicine, Vall d'Hebron University Hospital, Barcelona, Spain; SODIR, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁷ Paris 7 University Denis Diderot, Paris Sorbonne, Cité, Paris, France; Service de Maladies Infectieuses, CHU de Nice, Nice, France.
¹⁸ Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany; Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany; Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute-HKI, Jena, Germany.
¹⁹ Pulmonology Department, Hospital Clinic of Barcelona, University of Barcelona, Ciberes, IDIBAPS, ICREA, Barcelona, Spain.
²⁰ School of Medicine, Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
²¹ Ludwig Boltzmann Institute for Traumatology, the Research Center in Cooperation with AUVA, Vienna, Austria.
²² Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany.
²³ Department of Acute Care, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. Electronic address: h.r.bouma@umcg.nl.

PMID: 40409328
DOI: 10.1016/S2213-2600(25)00124-9

Review

Sepsis in patients who are immunocompromised: diagnostic challenges and future therapies

Stefanie Deinhardt-Emmer et al. Lancet Respir Med. 2025 Jul.

. 2025 Jul;13(7):623-637.

doi: 10.1016/S2213-2600(25)00124-9. Epub 2025 May 20.

Authors

Affiliations

¹ Institute of Medical Microbiology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany.
² Department of Anesthesia and Critical Care, Lariboisière Hospital, APHP, Paris, France; Université Paris Cité, Inserm UMRS 942 Mascot, Paris, France.
³ Department of Intensive Care Medicine, Inselspital, University of Bern, Bern University Hospital, Bern, Switzerland.
⁴ Department of Trauma, Hand, and Reconstructive Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁵ Department of Translational Immunology and Experimental Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland.
⁶ Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
⁷ Department of Anaesthesiology, University Medical Center Göttingen, Göttingen, Germany.
⁸ Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
⁹ Center for Experimental and Molecular Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Department of Medicine, Division of Infectious Diseases, Amsterdam University Medical Center, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, Netherlands.
¹⁰ Department of Anesthesiology, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
¹¹ Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
¹² 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece; Hellenic Institute for the Study of Sepsis, Athens, Greece.
¹³ Department of Anesthesiology and Intensive Care Medicine Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁴ Department of Anesthesiology and Intensive Care Medicine, University Hospital of Modena, University of Modena and Reggio Emilia, Modena, Italy.
¹⁵ Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei hospital, University of Malta, Malta; Centre for Molecular Medicine and Biobanking, Biomedical Sciences, University of Malta, Malta.
¹⁶ Department of Intensive Care Medicine, Vall d'Hebron University Hospital, Barcelona, Spain; SODIR, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁷ Paris 7 University Denis Diderot, Paris Sorbonne, Cité, Paris, France; Service de Maladies Infectieuses, CHU de Nice, Nice, France.
¹⁸ Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany; Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany; Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute-HKI, Jena, Germany.
¹⁹ Pulmonology Department, Hospital Clinic of Barcelona, University of Barcelona, Ciberes, IDIBAPS, ICREA, Barcelona, Spain.
²⁰ School of Medicine, Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
²¹ Ludwig Boltzmann Institute for Traumatology, the Research Center in Cooperation with AUVA, Vienna, Austria.
²² Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany.
²³ Department of Acute Care, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. Electronic address: h.r.bouma@umcg.nl.

PMID: 40409328
DOI: 10.1016/S2213-2600(25)00124-9

Abstract

Sepsis is a life-threatening, dysregulated host response to infection. Immunosuppression is a risk factor for infections and sepsis. However, the specific immune derangements elevating the risk for infections and sepsis remain unclear in the individual patient, raising the question of whether a general state of immunosuppression exists. In this Review, we explore the relationship between immunosuppression and sepsis, detailing the definitions, causes, and clinical implications. We address the effect of primary immunodeficiencies, acquired conditions, and drugs on the risk of infection and the development of sepsis. Patients with sepsis who are immunocompromised often present with atypical symptoms and diagnostic test results can differ, making early recognition difficult. Future perspectives entail novel biomarkers to improve early sepsis detection and tailored treatments to modulate immune function. Including patients who are immunocompromised in clinical trials is crucial to enhance the relevance of research findings and improve treatment strategies for this vulnerable population.

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Conflict of interest statement

Declaration of interests BGC received speaker fees from Baxter. WJW discloses institutional funding from AstraZeneca, the EU (Eurostars), and The Netherlands Organisation for Health Research and Development. HRB discloses unrestricted institutional funding from Becton Dickinson, Inflammatix, Octapharma, OSAsense, MeMed, Dutch Kidney Foundation, Dutch Research Council; is a board member of SepsisNet society (non-profit, unpaid) and International Hibernation Society (non-profit, unpaid); is a member of Bebo, the institutional review board (financial compensation for time paid to institute); and is mentioned as inventor on a patent for chromanol-based compounds to prevent sepsis-associated organ failure (WO2021246868). MAW received grants from Deutsche Forschungsgemeinschaft and Bundesministerium für Bildung und Forschung; consulting fees from Merck & Co, Gilead, Pfizer, Shionogi, Eumedica, Coulter, Biotest, Sedana, Swedish Orphan Biovitrum (SOBI), and Boehringer Ingelheim; and payment or honoraria for lectures, presentations, or educational events from Merck & Co, Gilead, and Pfizer. He is also a patent owner for Delta like ligand for diagnosing severe infections (EP17185036.5 and EP17198330.7) and is the Secretary in General of the German Sepsis Society and Vice President of Paul-Ehrlich-Gesellschaft. MSW discloses unrestricted funding from Grifols, Sartorius, Sphingotec, Gilead, and Amomed; receives funding from the German Research foundation; and participated in an advisory board of Gilead. SC has participated in an advisory board for Pfizer and serves on the data monitoring committee for the TILIA trial (sponsored by AstraZeneca). BPS received funds from the European Society of Intensive Care Medicine and Xjenza Malta Research Excellence Program (REP-2023–049; REP-2024–062). JCS discloses institutional funding (full institutional disclosure) from Orion Pharma, Abbott Nutrition International, B Braun Medical, Swiss Center for Electronics and Microtechnology, Edwards Lifesciences Services, Kenta Biotech, Maquet Critical Care, Omnicare Clinical Research, Nestle, Pierre Fabre Pharma, Pfizer, Bard Medica, Abbott, Anandic Medical Systems, Pan Gas Healthcare, Bracco, Hamilton Medical, Fresenius Kabi, Getinge Group Maquet, Dräger, Teleflex Medical, GlaxoSmithKline, Merck & Co, Eli Lilly, Baxter, Astellas, AstraZeneca, CSL Behring, Novartis, Covidien, Philips Medical, Prolong Pharmaceuticals and Nycomed, Phagenesis, and Cytel, outside of the submitted work. JCS is the principal investigator of the planned randomised controlled trial RESTORE (sponsor HEMOTUNE, Zürich, Switzerland) and chair of the clinical advisory board of HEMOTUNE. MK discloses institutional funding (full institutional disclosure) from Reumafonds, Medisieve, Comentis, Abionic, CytoSorbents, Adrenomed, Inflammatix, SurvivX, and 4TEEN4 as well as travel reimbursements, speaker, and consulting fees from ARTCLINE, Atriva, AOP pharma, Inflammatix, SurvivX, and 4TEEN4. All other authors declare no competing interests.

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Sepsis in patients who are immunocompromised: diagnostic challenges and future therapies

Affiliations

Sepsis in patients who are immunocompromised: diagnostic challenges and future therapies

Authors

Affiliations

Abstract

Conflict of interest statement

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Medical