Clinical validation of an AI-based blood testing device for diagnosis and prognosis of acute infection and sepsis

Oliver Liesenfeld^{1

2}, Sanjay Arora³, Tom P Aufderheide⁴, Casey M Clements⁵, Elizabeth DeVos⁶, Miriam Fischer⁷, Evangelos J Giamarellos-Bourboulis⁸, Stacey House⁹, Roger L Humphries¹⁰, Jasreen Kaur Gill¹¹, Edward Liu¹², Sharon E Mace¹³, Larissa May¹⁴, Edward Michelson¹⁵, Tiffany M Osborn⁹, Edward Panacek¹⁶, Richard E Rothman¹⁷, Wesley H Self¹⁸, Howard A Smithline¹⁹, Jay Steingrub¹⁹, Paul Van Heukelom²⁰, Alexandra Weissman²¹, Matthew Wilson⁷, Donna M Wolk²², David W Wright²³, Ljubomir Buturovic²⁴, Yehudit Hasin-Brumshtein²⁴, Nandita Damaraju²⁴, Cici Lu²⁴, Joshua R Shak²⁴, Natalie N Whitfield²⁴, Purvesh Khatri^#^{25

26}, Timothy E Sweeney^#²⁴, Nathan I Shapiro^#²⁷

Affiliations

¹ Clinical Affairs, Inflammatix, Inc., Sunnyvale, CA, USA. oliver.liesenfeld@gmail.com.
² Institute of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. oliver.liesenfeld@gmail.com.
³ Department of Emergency Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵ Department of Emergency Medicine, Mayo Clinic, Rochester, MN, USA.
⁶ Department of Emergency Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA.
⁷ Department of Emergency Medicine, Georgetown University School of Medicine, Medstar Washington Hospital Center, Washington, DC, USA.
⁸ 4th Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece.
⁹ Department of Emergency Medicine, Washington University, St. Louis, MO, USA.
¹⁰ Department of Emergency Medicine, University of Kentucky, Lexington, KY, USA.
¹¹ Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI, USA.
¹² Department of Emergency Medicine, Hackensack Meridian Health, Jersey Shore University Medical Center HOPE Tower, Neptune, NJ, USA.
¹³ Department of Emergency Medicine, Cleveland Clinic, Cleveland, OH, USA.
¹⁴ Department of Emergency Medicine, University of California, Davis, Davis, CA, USA.
¹⁵ Department of Emergency Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA.
¹⁶ University of South Alabama, Mobile, AL, USA.
¹⁷ Department of Emergency Medicine, Johns Hopkins University, Baltimore, MD, USA.
¹⁸ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁹ University of Massachusetts Chan Medical School-Baystate, Springfield, MA, USA.
²⁰ Department of Emergency Medicine, University of Iowa, Iowa City, IA, USA.
²¹ Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²² Geisinger Diagnostic Medicine Institute, Geisinger Commonwealth School of Medicine, Danville, PA, USA.
²³ Department of Emergency Medicine, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, GA, USA.
²⁴ Clinical Affairs, Inflammatix, Inc., Sunnyvale, CA, USA.
²⁵ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
²⁶ Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
²⁷ Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

^# Contributed equally.

PMID: 41028541
DOI: 10.1038/s41591-025-03933-y

Clinical validation of an AI-based blood testing device for diagnosis and prognosis of acute infection and sepsis

Oliver Liesenfeld et al. Nat Med. 2025.

. 2025 Sep 30.

doi: 10.1038/s41591-025-03933-y. Online ahead of print.

Authors

Affiliations

¹ Clinical Affairs, Inflammatix, Inc., Sunnyvale, CA, USA. oliver.liesenfeld@gmail.com.
² Institute of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. oliver.liesenfeld@gmail.com.
³ Department of Emergency Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵ Department of Emergency Medicine, Mayo Clinic, Rochester, MN, USA.
⁶ Department of Emergency Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA.
⁷ Department of Emergency Medicine, Georgetown University School of Medicine, Medstar Washington Hospital Center, Washington, DC, USA.
⁸ 4th Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece.
⁹ Department of Emergency Medicine, Washington University, St. Louis, MO, USA.
¹⁰ Department of Emergency Medicine, University of Kentucky, Lexington, KY, USA.
¹¹ Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI, USA.
¹² Department of Emergency Medicine, Hackensack Meridian Health, Jersey Shore University Medical Center HOPE Tower, Neptune, NJ, USA.
¹³ Department of Emergency Medicine, Cleveland Clinic, Cleveland, OH, USA.
¹⁴ Department of Emergency Medicine, University of California, Davis, Davis, CA, USA.
¹⁵ Department of Emergency Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA.
¹⁶ University of South Alabama, Mobile, AL, USA.
¹⁷ Department of Emergency Medicine, Johns Hopkins University, Baltimore, MD, USA.
¹⁸ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁹ University of Massachusetts Chan Medical School-Baystate, Springfield, MA, USA.
²⁰ Department of Emergency Medicine, University of Iowa, Iowa City, IA, USA.
²¹ Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²² Geisinger Diagnostic Medicine Institute, Geisinger Commonwealth School of Medicine, Danville, PA, USA.
²³ Department of Emergency Medicine, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, GA, USA.
²⁴ Clinical Affairs, Inflammatix, Inc., Sunnyvale, CA, USA.
²⁵ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
²⁶ Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
²⁷ Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

^# Contributed equally.

PMID: 41028541
DOI: 10.1038/s41591-025-03933-y

Abstract

Lack of reliable diagnostics for the presence, type and severity of infection in patients presenting to emergency departments with non-specific symptoms poses considerable challenges. We developed TriVerity, which uses isothermal amplification of 29 mRNAs and machine learning algorithms on the Myrna instrument to determine likelihoods of bacterial infection, viral infection and need for critical care interventions within 7 days. To validate TriVerity, the SEPSIS-SHIELD study enrolled 1,222 patients with clinically adjudicated infection status and need for critical care intervention within 7 days as endpoints. The TriVerity Bacterial and Viral scores had higher accuracy than C-reactive protein, procalcitonin or white blood cell count for the diagnosis of bacterial infection with area under the receiver operating characteristic (AUROC) of 0.83, and viral infection (AUROC = 0.91). The TriVerity Severity score had an AUROC of 0.78 for predicting illness severity and allowed reclassification of risk for critical care interventions compared to clinical assessment (quick Sequential Organ Failure Assessment) alone. Each of the three scores had rule-in specificity >92% and rule-out sensitivity >95%. Comparison of antibiotics administration at presentation with post-follow-up adjudication found that TriVerity could potentially reduce false positives and false negatives for inappropriate antibiotics use by 60-70%. Further clinical testing in an interventional setting is needed to prove actionability and clinical benefit of TriVerity.

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Conflict of interest statement

Competing interests: The institutions of all principal investigators received research support for the conduct of the current SEPSIS-SHIELD study. O.L. is an advisor to and owns stock options in Inflammatix, Inc. T.A. holds unrestricted research grants for clinical trial implementation from the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, the National Heart, Lung, and Blood Institute, ZOLL Medical, Inflammatix, Cytovale, Abbott and AstraZeneca; received equipment support for unrestricted clinical trial implementation from ZOLL Medical and Moberg ICU Solutions; and received honoraria for consultanting from Medtronic. C.C. received honoraria for research consultation from Inflammatix and Vail Scientific. E.J.G.-B. has received honoraria from Abbott Products Operations, bioMérieux, Sobi and Thermo Fisher Brahms; independent educational grants from Abbott Products Operations, bioMérieux, Gentian, InCyte, Merck Sharp & Dohme, Novartis, UCB, PHC Europe BV and Swedish Orphan Biovitrum AB (publ) (Sobi); and funding from the Horizon 2020 European grants ImmunoSep and RISCinCOVID and the Horizon Health grant EPIC-CROWN-2, Homi-LUNG and POINT (granted to the Hellenic Institute for the Study of Sepsis or to the National and Kapodistrian University of Athens). L.M. received honoraria for speaking engagements from Inflammatix. T.O. received funding from Beckman Coulter and participated in the Centers for Medicare and Medicaid Services Measure Instrument Development and Support (MIDS) patient safety project: Sepsis Outcome Measure Technical Expert Panel. R.E.R. received remuneration for participation on advisory boards for Inflammatix, Cytovale, MeMed, Cepheid, Roche and Immunexpress. He served as site principal investigator for Johns Hopkins University with grant support for study activities for other Inflammatix-sponsored research and conducted sponsored research from Cytovale, MeMed, Beckman Coulter, Abbott and Immunexpress. R.E.R. also participated in national educational conferences with paid remuneration from Inflammatix and Cepheid. W.S. reports receiving payment from Inflammatix in 2019 for serving on a scientific advisory board. A.W. received consultation fees from Inflammatix. L.B, Y.H.B., N.D. and N.N.W. are employees and stock option holders of Inflammatix. C.L. and J.R.S. hold stock options in Inflammatix. P.K. is a co-founder of, a consultant to and a scientific advisor to Inflammatix. T.E.S. is a co-founder, employee and stock option holder of Inflammtix. N.S. received funding from Bluejay Diagnostics and Inflammatix and reports personal financial interest in Prenosis. S.A., E.D., M.F., S.H., R.H., J. K.G., E.L., S.M., E.M., E.P., H.S., J.S., P.V., M.W., D.M.W. and D.W.W. declare no conflicts of interest or relevant competing interests.

References

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75A50119C00034, 75A50119C00044, and 75A50122C00069/U.S. Department of Health & Human Services | Biomedical Advanced Research and Development Authority (BARDA)

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Clinical validation of an AI-based blood testing device for diagnosis and prognosis of acute infection and sepsis

Affiliations

Clinical validation of an AI-based blood testing device for diagnosis and prognosis of acute infection and sepsis

Authors

Affiliations

Abstract

Conflict of interest statement

References

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials