Researchers Uncover Viral Role in Sepsis

During the first 33 months of the COVID-19 pandemic, SARS-CoV-2 accounted for 1 in 6 episodes of sepsis, underscoring the significance of viral sepsis, according to a recent study headed by experts at the Harvard Pilgrim Health Care Institute. The conclusion of Sepsis Awareness Month and the release of the report serve as a timely reminder of the value of sepsis research.

The study, “Use of Electronic Clinical Data to Track Incidence and Mortality for SARS-CoV-2-Associated Sepsis”, was published in JAMA Network Open.

Severe infection that results in organ failure is referred to as sepsis. It is a major contributor to death, disability, and inflated medical expenses. Although the majority of medical professionals and academics link sepsis to bacterial infections, the COVID-19 pandemic has shown that viral infections can also play a significant role in sepsis development. Few studies, however, have examined how much of a burden viral infections add to sepsis overall and how individuals with viral sepsis fare compared to those with bacterial sepsis.

 “Previous efforts to quantify the burden of SARS-CoV-2-associated sepsis have been limited by inconsistent definitions and under-recognition of viral sepsis,” said senior author Chanu Rhee, Harvard Medical School Associate Professor of Population Medicine at the Harvard Pilgrim Health Care Institute. “Our prior research has shown that electronic health record (EHR)-based surveillance using clinical markers of infection and organ dysfunction can provide more accurate estimates of sepsis incidence and outcomes compared to using hospital discharge diagnosis codes, but this method had not previously been applied specifically for sepsis associated with SARS-CoV-2 or other viruses.”

The study researchers performed a retrospective cohort study using EHR data for all adults admitted to five Massachusetts hospitals between March 2020 and November 2022. The team quantified the incidence and in-hospital mortality for sepsis associated with SARS-CoV-2 infections using clinical criteria adapted from CDC’s sepsis surveillance definition that incorporated positive SARS-CoV-2 tests and clinical signs of organ dysfunction. They found that approximately 1 in 6 cases of sepsis were associated with SARS-CoV-2 during this period. The mortality rate for patients with SARS-CoV-2-associated sepsis was very high initially—33% over the first three months of the pandemic—but declined over time and eventually became similar to the mortality rate for presumed bacterial sepsis, a rate of about 14.5% that remained stable throughout the study period. The researchers also confirmed their electronic surveillance definition accurately identified cases of viral sepsis caused by SARS-CoV-2 infections using detailed medical record reviews.

“Our study draws attention to the high burden and poor outcomes associated with viral sepsis, while also demonstrating the utility of using EHR-based algorithms to conduct surveillance for both viral and bacterial sepsis”, said Claire Shappell, a former research fellow at the Harvard Pilgrim Health Care Institute and lead author of the study. Dr. Shappell, now a Harvard Medical School Instructor of Medicine in the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital, adds, “Current sepsis treatment protocols often presume sepsis is caused by bacteria and suggest treating all patients with sepsis with broad-spectrum antibiotics and intravenous fluids. We hope our findings will highlight that sepsis is not a “one-size-fits-all” entity, but one that requires clinicians to tailor their diagnosis and treatment strategy to each patient’s syndrome and probable pathogen.”