U-M Researchers Find Drug to Calm Fatal Response to COVID-19

Researchers at the University of Michigan in Ann Arbor have found a drug that can calm the body’s overreactive immune response to COVID-19 and save lives.
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tocilizumab and COVID-19 graphic
U-M researchers have found that tocilizumab can calm the body’s often fatal overreaction to COVID-19. // Image courtesy of the University of Michigan

Researchers at the University of Michigan in Ann Arbor have found a drug that can calm the body’s overreactive immune response to COVID-19 and save lives.

Critically ill COVID-19 patients who received a dose of intravenous tocilizumab were 45 percent less likely to die overall compared to those who didn’t receive the drug, and they were more likely to be out of the hospital or off a ventilator one month after treatment.

The lower risk of death in patients who were treated with the drug occurred despite the fact that they also had twice the risk of developing an additional infection on top of COVID-19.

The study suggests the drug can calm the cytokine storm, in which the immune system overreacts to the virus and can cause death. Tocilizumab was originally designed for rheumatoid arthritis and has already been used to calm the overreaction in patients receiving advanced immunotherapy treatment for cancer.

The researchers based their findings on a look at data from 154 critically ill patients treated at Michigan Medicine, U-M’s academic medical center, from early March to late April. The analysis looked at patients’ records through late May. During that time, little was known about what would help COVID-19 patients on ventilators, and about half the studied patients received the drug. Most who received it did so within the 24-hour period surrounding their intubation.

While clinical trials are still needed to see if the drug truly provides a benefit, the two groups offered a natural opportunity for researchers to study their outcomes.

“One role of epidemiology is to rigorously evaluate real-world data on treatment effects, especially when evidence from clinical trials is not available,” says Emily Somers, lead author and an epidemiologist who has studied rheumatologic and immunologic diseases. “We kept trying to prove ourselves wrong as signals of benefit emerged in the data, both because of the immediate implications of these data, and in part because of concern about the supply of the medication for other patients. But the difference in mortality despite the increase in secondary infection is quite pronounced, even after accounting for many other factors.”

Somers also is an associate professor in the U-M Medical School’s department of internal medicine and member of the U-M Institute for Healthcare Policy and Innovation. She also co-leads the COVID-19 Rapid Response Registry.

The group developed treatment guidelines for doctors at Michigan Medicine in mid-March. The guidelines also pointed out the risk factors, so some doctors decided to use the medicine and others didn’t, creating the two groups and inadvertently setting the stage for a natural comparison.

Most of the patients were transferred to U-M from Detroit-area hospitals after diagnosis with COVID-19, and those who received tocilizumab were less likely overall to have been transferred while already on a ventilator.

By the end of the 28-day period after patients went on a ventilator, 18 percent of those who received the drug had died, compared with 36 percent of those who had not. When adjusted for health characteristics, this represents a 45 percent reduction in mortality. Of those still in the hospital at the end of the study period, 82 percent of the tocilizumab patients had come off the ventilator, compared with 53 percent of those who didn’t receive the drug.

In all, 54 percent of the tocilizumab patients had developed a secondary infection, mostly ventilator associated pneumonia, while 26 percent of those who didn’t receive tocilizumab developed such infections. Such “superinfections” usually reduce the chance of survival for COVID-19 patients.

Hydroxychloroquine was included in the treatment guidelines for COVID-19 inpatients at Michigan Medicine for the first 2.5 weeks of the study period, before being removed as evidence of its lack of benefit and risks emerged. In all, it was used in one-quarter of the patients who received tocilizumab and one-fifth of those who didn’t. Similar percentages of the two patient groups received steroids.

The patients in the two groups were similar in most ways except for a slightly higher average age in the non-tocilizumab group, and lower rates of chronic obstructive pulmonary disease and chronic kidney disease among the tocilizumab patients.

The study was published in the peer-reviewed journal Clinical Infectious Diseases after being available as a preprint in June. More information on the study is available here.

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