The reason severe COVID-19 is so deadly is that it unleashes a condition called sepsis.
Sepsis occurs when an abnormal immune response to an infection damages the body’s own tissues, leading to organ failure.
Of the 26,266 people who were hospitalized with COVID-19 in Pennsylvania in the first seven months of the pandemic, about 8,000, or 31%, also were diagnosed with sepsis, according to a new report from the Pennsylvania Health Care Cost Containment Council (PHC4).
Among COVID-19 patients with sepsis, almost 1 in 3 died, compared to about 1 in 12 who were not diagnosed with sepsis. The patients who survived sepsis spent an average of 13 days in the hospital, almost twice as long as patients without sepsis, PHC4 found.
Indeed, researchers say that life-threatening COVID-19 is, by definition, the same as sepsis because both involve immune system malfunctions that set off a disastrous cascade of low oxygen, low blood pressure, racing heart rate, elevated white blood cells, and excessive blood clotting. In some sepsis patients, there are high levels of powerful inflammation-causing “cytokines” that send the immune system into an overdrive, a so-called “cytokine storm.”
“Everyone with severe COVID-19 has sepsis,” said Ian Barbash, a pulmonary and critical care specialist at the University of Pittsburgh Medical Center. “Most of the treatments for severe COVID-19 are really targeting the immune system response rather than the coronavirus.”
Mark Mikkelsen, chief of the University of Pennsylvania Health System’s critical care section, noted that only a small percentage of people diagnosed with COVID-19 wind up in a hospital. “But if they need hospitalization, there is a tremendous overlap with sepsis.”
Only two treatments that tamp down the immune response — the steroid dexamethasone and the rheumatoid arthritis drug tocilizumab — have been authorized to treat COVID-19, and they are only moderately effective. Remdesivir, which targets the actual virus, has also shown modest benefit.
“Remdesivir and dexamethasone can’t hold a candle to the importance of avoiding COVID-19 by getting vaccinated,” Barbash said. “Among the small number who might become infected after vaccination, the chances of ICU admission or death is vanishingly small. "
Mikkelsen agreed: “The true way to fight this infection is to prevent it.”
The history of the word sepsis goes back to ancient Greece. Sepsis comes from the Greek word “sepo,” which means “I rot.” The first medical use of “sepo” was in the Homeric poems.
Even before the coronavirus pandemic, studies showed sepsis was the leading cause of death in U.S. hospitals; annual costs of treatment and, for survivors, rehabilitation were estimated at $62 billion.
Like the human immune response, sepsis is complex and somewhat idiosyncratic, which makes it difficult to recognize and diagnose before it becomes life-threatening. The definition and treatment guidelines have evolved to try to improve outcomes, with the last major revision in 2016.
Along with that evolving guidance, medical training and awareness campaigns — notably Surviving Sepsis, launched in 2002 by critical care societies around the world — have reduced death rates for sepsis.
However, sepsis usually arises from infections caused by bacteria. Antibiotics are highly effective against such infections if given early enough.
Viral infections are a different story. Every year in the U.S., thousands of Americans die of sepsis caused by flu viruses. The novel coronavirus that was first recognized in China in late 2019 is far more lethal and unpredictable.
“What’s different about COVID-19 is that people get it, then after a week or more, they may have to go the hospital, then several more days may pass before they’re in” intensive care, said Barbash. “The pace of the illness is very different than, for example, bacterial pneumonia.”
What’s more, COVID-19 patients often seem to be improving, only to go into a sudden, deadly spiral.
The risk of sepsis dramatically increases with age, as the PCH4 report shows. About a third of hospitalized COVID-19 patients over 65 were diagnosed with sepsis, compared to 22% of people age 25 to 44. Unlike so many other aspects of the pandemic, race and ethnicity did not seem to be a significant factor. The rates of sepsis for Asian, Black, Hispanic, and white patients all hovered around 30%.
“People should look at these data and get the vaccine,” Barbash said.