Molecules May Hold the Key to Faster, More Accurate Sepsis Diagnosis and Treatment

With a mortality rate of 25% to 30%, sepsis kills nearly 270,000 Americans annually and impacts at least 1.7 million adults. That’s according to the Centers for Disease Control and Prevention (CDC), which also reports that one in three patients who die in a hospital have sepsis.

While clinical and technological advances have helped accelerate the diagnosis and treatment of sepsis, its cause has remained a mystery. Now, however, Columbia University Irving Medical Center researchers may have found a clue revealing how an infection can spiral into sepsis. Their findings may ultimately help physicians determine which patients require immediate life-saving treatment.

Sepsis is caused by a microbial infection and dysregulated physiologic response. Its cascade effect can lead to organ system failure and, ultimately, death if treatment is delayed. The challenge to rapid diagnosis is that its presentation varies depending upon the source of the infection and, in some cases, the age of the patient. Further, the most common symptoms of sepsis—fever, tachypnea, tachycardia, hypotension, and signs of tissue hypoperfusion—are shared by numerous other conditions.

To diagnose sepsis, clinicians currently rely on history, clinical presentation, leukocytosis or leukopenia, and lactate level; blood and other cultures. Imaging may also be done as an adjunct to identify the source of sepsis. Ultimately, the septic patient’s prognosis depends on early identification and treatment, response to treatment, and severity at presentation.

Columbia University researchers, in a study in Nature, found that two specific microRNA molecules may be potential biomarkers of poor prognosis and indicate the need for more intensive treatment.  Specifically, in a search to understand the why the body’s innate immune response to sepsis shuts down, researchers discovered that miR-221 and miR-222 are produced in immune cells during prolonged inflammation. These microRNAs silence inflammatory gene expression and, in a mouse model of sepsis, suppress the immune system when it is most needed.

They went on to study 30 hospitalized patients and found that those with evidence of organ failure exhibited higher levels of miR-221 and miR-222 in their blood samples. Patients with elevated miR-221 and miR-222 also exhibited evidence of immunosuppression. Researchers surmised that these microRNAs could help physicians distinguish between those patients in organ failure who are at high risk of death and those whose infections were milder.

“When doctors face sepsis in the hospital, it is usually a mystery as to what is causing the infection, but they must act quickly. They can choose to use the broadest spectrum of antibiotics for an aggressive approach to cover every bacterial cause of infection, but this may later cause antibiotic resistance, a growing problem,” said co-author Daniel Freedberg, MD, assistant professor of medicine at CUIMC, in a blog on the study. “Any test that can identify the cause of sepsis to guide treatment options is invaluable.”

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