ISICIP 2025 Symposium – In collaboration with Viva In Vitro Diagnostics
The symposium “NLRP3 Inflammasome: The Missing Link in Sepsis Survival”, held within the 29th International Symposium on Infections in the Critically Ill Patient (ISICIP 2025), brought together leading experts in immunology and critical care to discuss one of the most promising frontiers in sepsis research: the functional measurement of immune system activity.
Moderated by Dr. Ricard Ferrer Roca, Head of Intensive Care at Vall d’Hebron University Hospital, the session featured Prof. Evangelos Giomarellos (University of Athens) and Prof. Pablo Pelegrín (University of Murcia, IMIB and co-founder of Viva In Vitro Diagnostics). Together, they explored how NLRP3 inflammasome dysfunction shapes patient outcomes and how new diagnostic technologies, such as VIVA-ELISA®, can bring immunological precision to the bedside.
This full transcription reflects the exchange of scientific insights that marked one of the most dynamic and thought-provoking sessions of ISICIP 2025, highlighting the convergence between basic immunology and clinical decision-making in critical care.
Introduction and Opening
Dr. Ricard Ferrer Roca:
After the jingle—yes, I always forget about the jingle, which I think is also important—let’s continue.
Following this short coffee break, we move on with our second very intense day here at ISICIP 2025.
Now it’s time for the symposium organized in collaboration with Viva In Vitro Diagnostics.
Thank you for supporting this session and for your contribution to the entire meeting.
The title of this symposium is “NLRP3 Inflammasome: The Missing Link in Sepsis Survival.”
Why did we choose this title?
Because over the past two days we’ve talked a lot about sub-phenotyping, about identifying specific therapeutic targets, and about the importance of biomarkers in sepsis—biomarkers for diagnosis, for prognosis, and for enriching our studies and improving patient selection.
During the next 50 minutes, we’ll discuss the role of the NLRP3 inflammasome in all these aspects: early identification, stratification, and sub-phenotyping for therapeutic purposes.
We have two outstanding speakers for this session.
The first one is Professor Evangelos Giomarellos, from Greece.
You all know him well—he still has a smile on his face, and that smile reflects the optimism that all his work on translating sub-phenotypes into clinical practice might soon yield positive results.
He’s the perfect speaker for this session, moving us from molecular mechanisms to clinical phenotypes in sepsis.
Professor Giomarellos, the floor is yours.
We’ll leave the discussion for the end, so please stay with me after you finish, and then we’ll continue with the questions.
Thank you very much.
Prof. Evangelos Giomarellos
Prof. Evangelos Giomarellos:
Thank you for the kind words, for the invitation, and for giving me one more topic for which, honestly, there are still no definitive conclusions.
The idea is that we should start changing this.
Until now, we have usually tried to understand how a phenotype may be linked to a biomarker or to a clinical response.
Today I’d like to approach it from the opposite direction: to see how the molecular mechanisms can help us explain the phenotypes.
This is my disclosure slide, and I will begin by defining what we mean by a phenotype.
A phenotype, in the context of sepsis, is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
Although we traditionally associate sepsis with bacterial infection, this same definition applies to viral infections as well.
When we speak of phenotypes, we refer to the clinical manifestations that reflect how infection impacts various organs—respiratory, coagulation, hepatic, cardiovascular, neurological, and renal functions.
All these parameters together define a patient’s clinical phenotype.
I’m sure that everyone in this room knows or has read the landmark article that analysed six large patient cohorts—most from the United States, one from Germany, and some from past clinical trials, including the PROWESS trial from 2001.
The core idea of that analysis was that the clinical phenotype of the patient is what truly matters when evaluating outcomes.
However, we must remember that the standard of care twenty years ago was very different from what we have today, so survival data must be interpreted cautiously.
In those cohorts, patient characteristics varied considerably.
Some used the older Sepsis I definitions, others the Sepsis II criteria.
In the Sepsis II cohorts, to be enrolled, patients needed to meet criteria for severe sepsis—whereas under Sepsis III, an increase in SOFA score by two points is enough, even without a single organ failure.
Using a machine-learning approach with 24 clinical and laboratory variables—including vital signs, biochemical parameters, complete blood counts, and coagulation markers—researchers were able to cluster patients into four phenotypes: alpha, beta, gamma, and delta.
It’s not that each phenotype corresponds to one organ dysfunction, but rather that certain constellations of variables cluster together.
What’s remarkable is that across cohorts—particularly in the SENECA study—the delta phenotype consistently appears as the one associated with the worst prognosis.
The key questions are:
first, whether this can be replicated, and second, whether the phenotype correlates with the patient’s immune function.
We decided to replicate those findings in collaboration with Chris Seymour and my colleague Elena Karakike.
She applied the same algorithm to four bacterial-sepsis cohorts and two viral-sepsis cohorts (COVID-19).
The same four endotypes were again identified, and survival analyses confirmed that the delta phenotype carries the highest mortality.
Even when we reduced the model from 24 to just eight variables, the results were identical.
Now, something surprising emerged.
If the delta phenotype leads to higher mortality, one would expect higher concentrations of inflammatory biomarkers—IL-6, CRP, ferritin—right from day 0.
But in fact, those levels are essentially identical across phenotypes.
That means biomarker concentrations alone do not explain the functional differences we observe.
We may be looking at immune-functional phenotypes rather than simple biochemical profiles.
Let me illustrate this with another clinical study.
These were critically ill patients meeting the Sepsis III definition, randomized to receive either placebo or clarithromycin, in addition to standard of care, for four days.
By day 10, both the overall population and the subgroup achieving sepsis resolution showed an up-regulation of HLA-DR expression, suggesting partial restoration of immune function—essentially, recovery from immune paralysis.
Interestingly, among patients who survived the initial sepsis episode, those who had received clarithromycin showed a significantly lower risk of sepsis recurrence.
So, immunological restoration measured in the lab translated into a clinical benefit.
These patients all had very high SOFA scores—median around 10—with severe respiratory failure (PaO₂/FiO₂ < 200) and dysfunction in at least two additional organs.
Thus, what we were observing was not a general phenomenon but something specific to the subgroup with marked immune dysfunction.
Now, moving to the molecular level.
If we look inside the cell—specifically, a tissue macrophage—we see a phospholipid bilayer that separates the periplasmic space from the cytoplasm.
Within the cytoplasm resides a protein complex with three main domains: the leucine-rich repeat (LRR) domain, the NACHT domain, and the pyrin domain.
For those of us from regions where familial Mediterranean fever is prevalent, that pyrin domain immediately rings a bell, as mutations in the pyrin gene are well known to cause excessive inflammation.
Various danger signals—ATP, reactive oxygen species, double-stranded DNA, uric acid crystals, even Gram-positive bacteria—can enter the cell and bind to the LRR domain, triggering the assembly of the NLRP3 inflammasome.
This polymerisation recruits procaspase-1, which is cleaved into active caspase-1, leading to the processing of pro-IL-1β into its mature form, IL-1β.
IL-1β is never meant to be fully matured under normal conditions; if too much of it becomes active, a high-grade fever and uncontrolled inflammation result.
Therefore, only limited cleavage is physiologically tolerated.
However, when cells are “primed”—for example, in obesity, where Toll-like receptors 2, 1, and 4 are chronically stimulated by free fatty acids—small triggers such as monosodium urate can lead to excessive caspase activation and overproduction of IL-1β, fuelling systemic inflammation.
That’s why obese or diabetic patients are at higher risk for cytokine-storm syndromes in infections.
When IL-1β is overproduced, it can drive what we know as macrophage activation syndrome (MAS), sometimes referred to as a cytokine storm.
This syndrome features extremely high ferritin (from hepatic overproduction), decreased fibrinogen, elevated triglycerides, and activation of interferon-γ from NK cells—since IL-1β makes NK cells hyperactive, promoting hemophagocytosis in the bone marrow.
Clinically, these patients present with immunosuppression, high fever, hepatosplenomegaly, and multiple cytopenias—the more cytopenias, the more severe the condition.
This pattern differs from disseminated intravascular coagulation: MAS involves coagulopathy with liver dysfunction, which itself becomes an independent predictor of mortality.
Using the H-score developed by the American College of Rheumatology, a value above 169 greatly increases diagnostic specificity for MAS.
In our validation cohorts (Greek patients, cohorts A and B), MAS prevalence was about 4 %.
Finally, let me refer to the CANTOS trial, which I find one of the most remarkable studies ever conducted.
It involved post-myocardial-infarction patients with CRP > 2 mg/L who received either placebo or the monoclonal antibody canakinumab, an IL-1β blocker, every four months for five years.
The treatment significantly reduced recurrent cardiovascular events, confirming that chronic, subclinical inflammasome activation contributes to disease progression.
Taken together, these data show that inflammasome dysregulation—particularly NLRP3-mediated IL-1β overactivation—links metabolic comorbidities such as obesity and diabetes to inflammatory and cardiovascular outcomes.
There is no single universal phenotype in sepsis, but understanding these molecular pathways helps us connect the dots between clinical presentations and mechanistic biology.
Dr. Pablo Pelegrín
Prof. Pablo Pelegrín:
Thank you, Ricardo. First of all, thank you very much for this kind invitation. It’s a real pleasure to be here and to have the opportunity to present our results on sepsis and on the utility of the NLRP3 inflammasome.
I would also like to thank Evangelos for that excellent introduction to the world of the inflammasome.
This is my disclosure slide, and now I’ll give a slightly more biochemical and structural view of how the inflammasome works.
The inflammasome is mainly active in innate immune cells such as macrophages, monocytes, dendritic cells, and neutrophils.
A few years ago, our group described the structure of the inactive NLRP3 inflammasome.
In its resting state, this complex is compact and tightly folded; the pyrin domain—the one Evangelos mentioned—is buried in the centre of the structure.
When the inflammasome becomes activated, it undergoes a conformational change.
This cage-like complex opens up, and that opening is dangerous for the cell.
Why? Because the pyrin domain becomes exposed to the cytosol, where it can recruit the adaptor protein ASC.
ASC binds to the pyrin domain through a prion-like oligomerisation reaction: once one ASC binds, it changes conformation and allows the next ASC to bind, and so on, creating long filaments inside the cell.
These ASC filaments aggregate into large, highly visible complexes that we call ASC specks.
They can reach up to two microns in size and are easily observed under the microscope.
Why is this important?
Because once ASC filaments form, they recruit and activate caspase-1, a very potent enzyme that cleaves several proteins.
One of these targets forms pores in the plasma membrane, leading the cell to die by pyroptosis—a highly inflammatory form of programmed cell death.
Pyroptosis, as the name implies, is “fiery death.”
It’s inflammatory because caspase-1 also processes pro-IL-1β and pro-IL-18 into their mature forms, which then leak through those pores into the extracellular space, amplifying inflammation.
So, this process creates the perfect cocktail for a strong inflammatory reaction.
We now know that inflammasomes are implicated in over 200 different diseases:
chronic inflammatory conditions such as gout;
cardiovascular diseases;
metabolic disorders like diabetes;
and neurodegenerative diseases, including Alzheimer’s and Parkinson’s.
Most importantly for this audience, the inflammasome is a key player in the immune response to infection.
Whenever we face a pathogen—viral, bacterial, or fungal—the NLRP3 inflammasome helps trigger the early immune response that defends the host.
Given that septic patients experience a massive cytokine storm, one might assume that the inflammasome plays a central role.
However, early clinical trials with anti-cytokine therapies—such as anakinra (the IL-1 receptor antagonist), anti-IL-6, or anti-TNF biologics—failed.
They failed largely because patients weren’t stratified.
Everyone was treated the same, without distinguishing those who were hyper-inflammatory from those already in immune paralysis.
Now that we revisit those trials, we see that the hyper-inflammatory subgroup actually benefited.
But at the time, we didn’t have the biomarkers or functional tools to identify them.
After the initial inflammatory burst, many septic patients progress to immune paralysis, a state in which the immune system shuts down, making them highly susceptible to secondary infections.
New trials are exploring treatments for this stage—using recombinant interferon-γ or M-CSF, for example—but we still need reliable, early biomarkers to identify which patients are immunoparalysed.
That was our motivation: to find a functional biomarker capable of detecting immune paralysis.
We conducted three independent cohorts—the third one is still ongoing.
Any of you who wish to collaborate, we’d be happy to receive samples to help us validate our method.
We began with abdominal-sepsis patients.
These are critical cases that often develop in the hospital, which allows us to precisely track the onset of infection.
Timing is crucial, so we collected blood samples within the first 24 hours of sepsis onset, and then again at day 3, day 5, and at hospital discharge or recovery.
In our first study, published in 2019, we measured what everyone was measuring at the time—the cytokine storm.
Indeed, we found high plasma levels of IL-6, IL-8, HMGB1, and acute-phase proteins such as CRP and PCT.
Everything was elevated, but none of these markers distinguished which patients were immunoparalysed or predicted who would later die.
So we decided to change strategy.
Instead of measuring what was in the bloodstream, we decided to “ask the immune cells how they feel.”
When you see a patient, you ask, “How are you feeling?”
We asked the same question to their monocytes.
We isolated fresh monocytes from whole blood and tested how these cells responded to a second challenge—essentially simulating a secondary infection.
We activated the NLRP3 inflammasome in these monocytes ex vivo and measured two outputs:
- Formation of ASC specks inside the cells, and
- Release of IL-1β, the hallmark of inflammasome activation.
What we observed was striking: among septic patients, some were able to activate NLRP3 normally, while others completely failed to do so.
And we made these measurements just 24 hours after the onset of sepsis.
When we followed these patients over time, we found that those who failed to activate NLRP3—the non-responders—accounted for more than 80 % of deaths in that cohort.
Their mortality didn’t occur immediately; it started around day 10 and extended through the first month after infection.
This means we could stratify patients very early—within one day of sepsis onset—into those with intact immune responses and those in immune paralysis.
At that same 24-hour point, CRP, SOFA scores, IL-6, or any other systemic biomarker showed no difference between these groups.
All patients were hyper-inflammatory on paper, but only some had immune cells that still worked.
We validated these findings in a second independent cohort.
Using the refined version of our assay, we again saw a clear separation between septic patients who responded normally and those who did not activate the inflammasome.
The non-responders—the ones with NLRP3 dysfunction—had higher mortality and more severe disease.
They spent longer in the intensive care unit, required more days of mechanical ventilation, and had longer overall hospital stays.
So this biomarker not only predicts mortality but also correlates with clinical severity.
When we analysed all the biomarkers we measured and performed ROC and bias analyses, the NLRP3 activation ex vivo test showed the highest sensitivity and specificity for identifying immunoparalysed patients.
In contrast, conventional biomarkers such as ferritin, PCT, or CRP failed to discriminate them.
We also used computational clustering, feeding all the data into a machine-learning model.
Each dot represented an individual patient, and what we observed was that those with defective inflammasome activation grouped together—they formed a distinct cluster, separate from those with a functional NLRP3 response.
In other words, functional inflammasome measurement identifies a unique subset of septic patients who had not previously been recognised by classical biomarkers.
We are now expanding our validation beyond abdominal sepsis, including respiratory and renal sepsis cases.
Although the number of patients in these categories is still limited, the preliminary data show the same pattern: in every type of sepsis, there is a subgroup of patients whose NLRP3 activation is decreased.
Another important aspect is that we can follow inflammasome activity over time.
In patients who survive, we see that their inflammasome function gradually recovers.
For example, after four months of recovery, these same patients show a restored capacity to activate NLRP3.
This demonstrates that the defect is not genetic—it’s transient and linked to the septic episode itself.
This led us to consider clinical decision points.
One of the most critical is hospital discharge.
We evaluated patients with very low inflammasome activation at day 1 and again at the time of discharge.
Some of them had already recovered normal inflammasome activity, but others remained at very low levels.
Those with persistently low NLRP3 activation were re-hospitalised within days or weeks, often with severe secondary infections.
Some even had life-threatening complications.
This means it’s essential to assess immune competence before discharge.
Measuring NLRP3 inflammasome activity can help determine whether a patient is ready to leave the hospital safely.
It’s a sensitive functional marker for identifying immunocompromised septic patients.
To summarise, critically ill patients with sepsis can develop immune paralysis even while showing high levels of inflammatory biomarkers in the blood.
They may have elevated CRP, PCT, IL-6—everything looks “activated”—but their immune cells are no longer responding to a second challenge.
The NLRP3 inflammasome activity provides a rapid, functional readout of this immune paralysis.
You can measure it within the first 24 to 72 hours, and it correlates strongly with long-term complications and mortality.
This opens the door for early interventions with novel therapies aimed at restoring immune function, such as recombinant interferon-γ or M-CSF, and helps clinicians decide when immunomodulatory treatments are appropriate.
It can also guide critical decision-making, such as hospital discharge, timing of immunostimulatory therapy, or inclusion in clinical trials.
Importantly, this biomarker tells us something that plasma cytokine measurements never can: it reveals how the immune cells are actually functioning—not just what molecules are floating in the bloodstream.
As I like to say, it’s like asking the immune system directly, “How are you feeling today?”
Before closing, I’d like to acknowledge all the people in my lab who made this possible—especially Laura, Juan, and Elio, who led most of these experiments—and, of course, the hospitals and funding agencies that helped us obtain the samples and conduct this research.
Thank you very much for your attention. I’ll be happy to take questions.
Discussion and Q&A Session
Dr. Ricard Ferrer:
Thank you, Pablo.
The topic is now open for discussion.
Does anyone want to start?
Prof. Antonelli:
First of all, thank you both for your beautiful presentations—really fascinating.
You’ve illustrated all the mechanisms behind these clinical observations.
But as a simple clinician, I must admit I’m a bit confused.
What should I actually measure? The inflammasome? Interferon-gamma? IL-6? Something else?
Can you give me a practical suggestion—maybe for the future?
Prof. Pablo Pelegrín:
That’s a very good question, and that’s exactly why we, as scientists, are measuring many different things—to understand which ones truly matter and can be translated into clinical practice.
What we’ve found is that measuring the activity of the NLRP3 inflammasome serves as a very reliable sensor of immune-cell function.
If immune cells are not working properly—and we can quantify this through specific parameters—the patient is at greater risk for complications and secondary infections.
The good news is that measuring inflammasome activity is relatively simple and fast.
We’re developing ELISA-like assays that can quantify NLRP3 activation.
These tests are not expected to be more expensive than standard IL-6 measurements and could soon be used routinely to assess immune competence in septic patients.
Prof. Evangelos Giomarellos:
Pablo, congratulations again on that excellent presentation.
I was wondering—could the downregulation of NLRP3 be an epiphenomenon of general immune paralysis rather than something specific to IL-1?
For instance, if you stimulate those same cells only with LPS, do they still produce TNF?
And what about their HLA-DR expression?
Prof. Pablo Pelegrín:
That’s a very relevant question.
We do see a reduction in TNF and IL-6 production as well, but the best segregation between immune-competent and immunoparalysed patients comes from measuring NLRP3 activity.
It shows higher sensitivity and specificity than other cytokines.
So yes, it’s a good marker of overall immune paralysis, but the NLRP3 signal seems to be particularly sensitive and specific.
Regarding IVDR certification—we’re working towards it.
The assay is designed for in vitro diagnostic validation in sepsis, though it could also be applied to other diseases, such as autoimmune disorders, where inflammasome overactivation plays a role.
Ultimately, if we want to talk about immune paralysis, we need functional evidence that immune cells aren’t working—and that’s exactly what the NLRP3 assay provides.
Audience Member 1:
Fantastic presentations. Thank you.
I have a question: it’s known that patients with severe sepsis and a hyperinflammatory phenotype have higher mortality compared to hypoinflammatory ones.
In your data, how does the immune depression you’ve described relate to short-term outcomes?
I understand that for long-term outcomes it’s critical, but what about the acute phase—when patients are first admitted to the ICU?
Prof. Pablo Pelegrín:
Great point.
What we’ve seen is that patients who die during the hyperinflammatory phase—those who die early—actually show higher NLRP3 activation at the beginning.
Their Toll-like receptor pathways are extremely active, leading to the cytokine storm.
However, very soon afterwards, their immune cells shut down.
That’s when the deactivation phase begins.
For these patients, therapies like anti-IFN-γ antibodies, canakinumab, or anakinra could be effective, but only if we’re sure the immune cells are still functional.
If you give immunosuppressive drugs to a patient whose immune system is already exhausted, you worsen the situation.
So functional testing before treatment is crucial.
Dr. Salvatore Coduli (Rome):
Thank you, Pablo, for your great talk.
I have two questions.
First, have you checked whether using a different trigger—other than endotoxin—would give the same non-response pattern or immune paralysis?
And second, have you identified any drugs, aside from those for sepsis recovery, that could modulate this system?
Prof. Pablo Pelegrín:
Yes, both are very interesting questions.
To the first one: yes, we’ve tested alternative triggers of NLRP3 activation.
Some take longer incubation times, but the results are consistent.
We chose a short activation protocol to make the assay faster and more clinically feasible.
Even LPS alone, if incubated long enough, can activate NLRP3 in human monocytes—it’s completely feasible.
We also tested other inflammasomes, such as the Pyrin inflammasome, which remain functional even when NLRP3 is compromised.
This provides internal controls showing that the cells are viable and capable of responding through other pathways.
Regarding drugs, yes—there are now several promising NLRP3 inhibitors in Phase 2 and 2b clinical trials.
Some are being tested specifically in sepsis, especially in septic patients with renal failure.
So it becomes critical to measure inflammasome activation before using these inhibitors; otherwise, you might suppress an already suppressed pathway.
Conversely, in immunoparalysed patients, recombinant cytokines like IFN-γ or M-CSF can “reboot” the immune system, while in hyperinflammatory phenotypes, we might use anti-cytokine therapies.
The key is knowing which patient belongs to which group.
Audience Member 2:
Thank you both for the fascinating discussion.
I have the same question for both of you:
are you confident that these findings are reproducible across different infection types—say, abdominal vs. pulmonary—or different pathogens?
It’s hard to believe there’s a single common mechanism for every microorganism.
Prof. Evangelos Giomarellos:
You’re absolutely right—it’s unlikely that all infections behave identically.
When I design a clinical trial, I’m always cautious about whether patients have abdominal sepsis or not, because the need for source control can confound results.
Likewise, lung infections vary greatly: community-acquired pneumonia is very different from hospital- or ventilator-acquired pneumonia.
So yes, I agree—different pathogens likely trigger distinct immune patterns.
Even if current biomarkers appear similar, that doesn’t mean the underlying mechanisms are the same.
We shouldn’t generalize too much; we need more stratified studies per infection type.
Dr. Ricard Ferrer:
That’s a key point.
During COVID, it was simpler—we were all dealing with the same infection, the same pathogen, across all ICUs.
But now, with mixed patients, stratification is essential for meaningful results.
There’s another issue I’d like to raise—something that’s come up throughout the conference.
We intensivists often focus on the acute phase of sepsis, but not enough on long-term outcomes.
What happens to patients after they leave the ICU?
Many remain in a frail immunological state.
Your research may help identify these patients and improve their long-term recovery.
At the moment, when a patient leaves intensive care, our responsibility often ends.
We need better continuity of care to ensure these survivors regain a healthy immune status.
Prof. Evangelos Giomarellos:
I agree completely.
When preparing a grant on what we called “long sepsis,” I reviewed all the available literature.
It was striking: among patients who survive the initial 90 days, fewer than 50% are still alive one year later.
Despite this, long-term sepsis research receives very little attention—much like long COVID at the beginning.
We need to change that.
Prof. Pablo Pelegrín:
Yes, exactly.
When patients go home, we know that many experience a kind of trained immunity or immune reprogramming after infection, which we’re not monitoring at all.
These changes could explain many of the long-term complications we see later.
We definitely need to continue following these patients beyond hospital discharge.
Dr. Ricard Ferrer:
And just to clarify, the new Phase 2 trials you mentioned, Pablo—those are mainly aimed at modulating hyperinflammation, not restoring the inflammasome itself, correct?
Prof. Pablo Pelegrín:
That’s correct.
Most of those drugs target hyperinflammatory pathways.
But our data suggest that for many patients, especially those in immune paralysis, the key will be to restore inflammasome function rather than block it.
Audience Member 3:
Congratulations again to both speakers.
I have one more question.
In our ICU we often treat septic patients who recently received chemotherapy or immunosuppressive drugs for autoimmune diseases.
How do you think those prior treatments influence the immune paralysis you’re measuring?
Prof. Pablo Pelegrín:
That’s a very important question.
Of course, prior immunosuppressive or chemotherapy treatments affect inflammasome function.
In our cohorts, we excluded such patients and waited long enough after chemotherapy or anti-inflammatory drug administration to ensure clearance from the body.
But in daily clinical practice, you will definitely encounter these cases.
We already know that glucocorticoids dramatically reduce NLRP3 activation in vivo.
We’re working on unpublished data that confirm this.
So, yes, prior treatment has a strong impact—and that’s precisely why functional immune assessment is needed.
You have to know whether your patient is immunoparalysed because of sepsis, or because of the therapy they received earlier.
In both cases, the phenotype looks similar.
Dr. Ricard Ferrer:
Thank you all.
I think we’ve covered an incredible amount of ground—from molecular mechanisms to patient management and long-term recovery.
We’ll close here and move to the next session.
Thank you again to Professor Giomarellos, Professor Pelegrín, and everyone who participated.
Closing Note
The discussion at ISICIP 2025 reaffirmed that sepsis is not a single disease but a dynamic spectrum of immune responses.
By focusing on the NLRP3 inflammasome as a functional biomarker, the research presented by Viva In Vitro Diagnostics and its collaborators opens new avenues for early stratification, patient monitoring, and personalized treatment.
As stated during the session, “asking the immune cells how they feel” may soon become as essential as any biochemical test.
Bridging molecular biology and clinical practice is no longer a theoretical ambition—it is the path toward improving survival and quality of life for patients facing sepsis worldwide.