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UPMC, Pitt part of virus breakthrough

Research shows corticosteroids can reduce risk of death

Inexpensive, easily available corticosteroids can reduce the risk of death for critically ill COVID-19 patients by 20 percent, according to announcements Wednesday by teams of researchers from around the world, including UPMC and the University of Pittsburgh School of Medicine — which headed the only U.S.-based group.

The findings, which have already resulted in a treatment update from the World Health Organization, come from seven clinical trials, including the UPMC-Pitt effort that involved 121 hospitals in eight nations — with all the trials confirming test results announced in June by researchers in the United Kingdom, according to a UPMC-Pitt news release and other sources.

“(Using corticosteroids) is the only treatment right now shown to reduce mortality” — although infection prevention remains key and a vaccine remains the long-term goal, Christopher Seymour, director of the Translational and Clinical Science Program at Pitt’s School of Medicine, said in a phone interview Wednesday.

COVID-19 can trigger an over-aggressive immune-system reaction, leading to fluid accumulation and damage in the lungs, and corticosteroids help “calm down the immune response to (such) inflammation,” said Seymour, co-author with UPMC-Pitt colleague Derek Angus of an article in the Journal of the American Medical Association, one of four in JAMA on Wednesday discussing the corticosteroid findings.

Corticosteroids have broad effects, and using them systemically is “like building a dam upstream of a waterfall,” Seymour said.

Corticosteroids are not recommended as treat­ment for COVID-19 patients who don’t need either supplemental oxygen or mechanical ventilation, according to various sources.

In total, the WHO-coor­dinated trials found that there were only 222 deaths among 678 patients who received corticosteroids and 425 deaths among 1,025 patients who received placebos or the “usual care,” according to a meta-analysis of the trials.

That generates an “odds ratio” of 0.66, according to the analysis.

The U.K. findings led all the other clinical trials to shift direction and provide all their participants with corticosteroids, because the strong indication of their effectiveness made it unethical to withhold the drug, said UPMC spokeswoman Allison Hydzik in a phone interview.

UPMC-Pitt re­search­ers were working on a “Randomized Embedded Multifactorial Adaptive Platform-Community Acquired Pneumonia” trial, which involved a large number of treatments, using artificial intelligence to steer those treatments in favor of ones that worked the best.

While everyone who qualified was given a corticosteroid after the U.K. findings, the REMAP trial continues with “thousands of different treatment regimens, including various doses and combinations of vitamin C, convalescent plasma, blood thinners, antivirals and immune modulators,” the UPMC-Pitt release stated.

Wednesday’s announcement represents the culmination of massive international cooperation that built not only on the U.K. study, but early pandemic findings in China and previous attempts to use corticosteroids for viral pneumonia, according to a JAMA editorial published Wednesday.

“The efforts of the clinical trial groups for the launch and conduct of high-quality trials in the midst of a pandemic should be acknowledged as an important accomplishment,” the editorial author stated. “The agreement among the trialists to share unpublished data with WHO is an example of how science can advance and is critical in the midst of what is likely to be numerous underpowered RCTs (Randomized Control Trials).”

Getting that cooperative work done “required established research in­frastructure, dedicated study teams and clinical equipoise that was often absent during the pandemic,” the author said.

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