Inflammatix Announces Three Landmark Publications in Nature Medicine that Redefine Acute Infection and Sepsis Diagnosis and Treatment

Inflammatix cracks the code of sepsis with an AI-powered test that outperforms the standard of care

SEPSIS-SHIELD study validates TriVerity™ as a breakthrough test that can transform hospital triage by providing early clarity on both infection type and illness severity

SUNNYVALE, Calif., Sept. 30, 2025 /PRNewswire/ -- Inflammatix, a pioneer in host-response diagnostics, today announced the publication of three manuscripts in Nature Medicine that will redefine how patients with suspected sepsis are diagnosed and treated, potentially offering faster answers for physicians, better outcomes for patients, and measurable cost savings for hospitals.

Sepsis is the leading cause of death in U.S. hospitals, yet billions spent on new tests, drugs, and policies have done little to improve survival or rein in rising healthcare costs. Early recognition is critical, but current protocols are rigid and controversial due to the lack of a clear definition of what counts as "sepsis" or "not sepsis."

"Neither 'sepsis' nor 'not sepsis' is clinically actionable," said Tim Sweeney, MD, PhD, co-founder and chief executive officer of Inflammatix. "Moreover, when someone presents with obvious sepsis, we can treat the infection with antibiotics, but we have no medicines to help them recover faster from critical illness. The three Nature Medicine publications mark a big paradigm shift in how we think about the diagnosis and care of patients with acute infection and sepsis. Inflammatix is moving the field of emergency medicine beyond traditional biomarkers and billing codes, bolstering clinical judgment through the embrace of AI-powered immune profiling as a new diagnostic and prognostic standard."

The publications include the pivotal results from the SEPSIS-SHIELD study (NCT04094818), which confirm the clinical and scientific utility of the company's flagship product, TriVerity™, a breakthrough molecular test that rapidly distinguishes between bacterial infection, viral infection, and non-infectious inflammation, and simultaneously predicts illness severity in patients with suspected acute infection or sepsis. With a demonstrated high sensitivity and specificity across more than 1,200 patients, the SEPSIS-SHIELD study shows that TriVerity arms emergency care teams with the diagnostic and prognostic guidance they need to make confident decisions at point-of-care — improving patient outcomes while reducing unnecessary resource use. Just as importantly, TriVerity provides hospitals with the defensible, biologically grounded evidence needed to avoid payment denials that erode revenue and delay care.

"TriVerity radically improves early decisions, telling clinicians whether patients need antibiotics, other diagnostics, or a higher level of care," added Dr. Sweeney. "That clarity can not only drive better outcomes, it also protects hospitals from costly denials. By delivering personalized, equitable, and rapid diagnostics when and where they're needed most, TriVerity empowers clinicians to put each patient in the right level of care, at the right time, with the right treatment — the core of effective triage."

TriVerity has earned both FDA Breakthrough Device Designation and, in January 2025, FDA 510(k) clearance.

The other Nature Medicine articles report on the development of two consortium consensus frameworks that establish sepsis as a set of distinct immunological states, providing a roadmap to treat the underlying cause of sepsis rather than as a billing diagnosis.

A Consensus Immune Dysregulation Framework for Sepsis and Critical Illness

The second Nature Medicine paper reports on the creation of the first consensus immune dysregulation network — called HI-DEF (Human Immune Dysregulation Evaluation Framework) — to identify shared biological pathways across critical illnesses including sepsis, acute respiratory distress syndrome (ARDS), trauma, and burns. Developed by the SUBSPACE consortium, which analyzed transcriptomic data from more than 7,000 patient samples across 37 cohorts worldwide, HI-DEF measures dysregulation in two key immune compartments: myeloid cells (e.g., neutrophils, monocytes) and lymphoid cells (e.g., T cells, natural killer cells). Using these two dysregulation scores, HI-DEF classifies patients into one of four states: (1) balanced, (2) myeloid-dysregulated, (3) lymphoid-dysregulated, or (4) system-wide dysregulated states.

Across datasets, disparate independent sepsis endotype schemas converged into four clusters, separating into "protective" versus "detrimental" responses driven by myeloid or lymphoid cells. HI-DEF was found to be highly predictive of illness severity and mortality: patients with myeloid or lymphoid dysregulation were 5-7 times more likely to die or require intensive care unit (ICU)-level care; mortality was highest among those with system-wide dysregulation. More importantly, analysis of multiple randomized control trials using HI-DEF scores found that the scores were associated with differential mortality in patients treated with immunomodulatory drugs such as anakinra and corticosteroids. Together, these results underscore the potential of HI-DEF for prognostic and therapeutic applications in EDs and ICUs.

"Identification of virtually identical conserved endotypes across critical illnesses by two international consortiums upends decades of failed research in sepsis, and in critical illnesses more broadly, due to biological and clinical heterogeneity in patients," noted Purvesh Khatri, PhD, professor of medicine at the Stanford School of Medicine, who is the co-corresponding author of the study. He is also co-founder and chief scientist at Inflammatix. "By moving beyond syndromic definitions and directly measuring immune cell dysfunction, HI-DEF offers a practical tool for precision medicine in the ICU. Physicians can use this framework as a roadmap for tailoring treatment plans and avoiding use of harmful therapies, giving patients better odds of survival through targeted use of powerful immune-modulating drugs. More broadly, HI-DEF can serve as a consensus model to guide future clinical trials and drug development. Used properly, adoption of HI-DEF can signal the beginning of precision medicine for the world's sickest patients."

A Consensus Blood Transcriptomic Framework for Sepsis

The third Nature Medicine paper reports that sepsis endotype schemas converge into three clusters — results that are similar to those observed with HI-DEF. The article describes the identification of three robust consensus transcriptomic subtypes (CTSs) of sepsis, referred to as CTS1, CTS2, and CTS3, based on an analysis of 2,142 blood samples from patients across four cohorts comparing three previously competing classification systems. The researchers noted that ICU mortality was highest within CTS2 (28.6%, compared to 16% in CTS1 and CTS3). Similarly to the HI-DEF framework, the CTS clusters also facilitated the identification of patients that may or may not respond to steroid treatment. Strikingly, the three CTS endotypes corresponded to three of the four HI-DEF endotypes, further demonstrating robustness across a diverse population of patients with sepsis.

"We are implementing TriVerity in our ER," said Edward A. Panacek, MD, professor and chair of Emergency Medicine at the University of South Alabama. "So much of national sepsis care today is more focused on meeting metrics rather than improving outcomes. We have never had a tool that can both improve patient care and reduce costs — until now. The collective results across three manuscripts show that host response can provide important guidance to physicians, who can now use a simple blood test like TriVerity to identify which patients with sepsis need aggressive therapy and which might be harmed by it. The results also suggest that drug companies can design smarter trials by targeting therapies to patients most likely to benefit. As a practical matter, the results support a move away from the 'one-size-fits-all' approach to sepsis care and toward the adoption of precision medical care in the ER and ICU, a shift that can save lives worldwide."

About the TriVerity™ Test System

The TriVerity™ Test System ("TriVerity"), Inflammatix's flagship in vitro diagnostic (IVD) test, includes the proprietary, disposable TriVerity cartridge and the Myrna™ instrument. TriVerity incorporates a panel of 29 patient messenger RNAs (mRNAs) to rapidly interpret the body's immune response to infection using machine learning-derived algorithms. TriVerity shows the likelihood of a bacterial infection, a viral infection, and illness severity in adult patients with suspected acute infection or sepsis that present to emergency departments. Results are delivered in approximately 30 minutes, guiding diagnosis and triage for adult ED patients with suspected acute infection or sepsis in the time frame ED providers need and expect. TriVerity empowers physicians to confidently make care decisions, which could influence the selection of antimicrobial therapy, focused workups with judicious laboratory and imaging orders, and patient admission or discharge disposition.

TriVerity was developed based on research conducted at the Stanford School of Medicine by Inflammatix co-founders Tim Sweeney, MD, PhD, and Purvesh Khatri, PhD, professor of medicine at the Stanford School of Medicine. Inflammatix holds exclusive rights to the core intellectual property, which is licensed from Stanford University.

About Inflammatix

Inflammatix, Inc., based in Sunnyvale, California, USA, is redefining molecular diagnostics by leveraging machine learning and host-response biology to generate accurate, actionable results. Backed by leading healthcare investors and federal support, the company aims to improve outcomes and lower costs through faster, smarter testing.

For more information, visit www.inflammatix.com and follow @Inflammatix_Inc on LinkedIn and X.

Government Support Acknowledgment
TriVerity™ was developed in part with funding from the U.S. Department of Health and Human Services; Biomedical Advanced Research and Development Authority (BARDA), under contracts 75A50119C00034, 75A50119C00044, and 75A50122C00069.

SOURCE Inflammatix