CRP Test Pinpoints Which COVID Patients Should Get Steroids

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Patients hospitalized with COVID-19 who have high levels of inflammation may benefit significantly from dexamethasone and other steroids, researchers say.

They warn, however, that patients with low levels of inflammation could face a significantly higher risk for severe outcomes with steroid use.

Lead author Marla Keller, MD, vice chair for research in the Department of Medicine at the Albert Einstein College of Medicine and the Montefiore system, New York City, and colleagues also found that a C-reactive protein (CRP) test can help physicians decide which patients are likely to benefit.

They published their findings online July 22 in Journal of Hospital Medicine.

In patients with high levels of inflammation — at least 20 mg/dL — steroid treatment was associated with a 77% reduction in the risk of needing mechanical ventilation or dying (odds ratio [OR], 0.23).

Importantly, treating with steroids when CRP levels were less than 10 mg/dL was associated with an almost threefold increased risk of going on mechanical ventilation or dying (OR, 2.64).

"The laboratory test could potentially be very helpful," Keller told Medscape Medical News.

Paper Builds on Randomized RECOVERY Findings

The work builds on findings of the large, randomized, open-label RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial in the United Kingdom. That study, with more than 6000 patients, found that dexamethasone, compared with standard of care, reduced deaths by about a third in ventilated patients and by about one fifth among people who needed oxygen therapy but were not on a ventilator.

The New York study confirmed findings of the RECOVERY trial but also that the benefits were true for steroids beyond dexamethasone.

Keller's team treated one group of 140 patients with steroids within 48 hours of hospital admission and compared results with a control group of 1666 similar patients who did not receive steroids. Most who received steroids got prednisone; some received dexamethasone and methylprednisolone.

Keller said their work led to developing a protocol for deciding who should get steroids that has changed practice throughout the Montefiore Health System.

"Opportunity to Save Many Lives"

She also said the results may have large implications for public health: "The RECOVERY trial and our study show that steroids reduce mortality," she said, adding that that knowledge and having a widely available indicator for when to administer the steroids gives "the opportunity to save many lives."

She acknowledged, however, that theirs is a single-institution study and more research must be done to narrow down which patients will benefit or be harmed most. They didn't look at, for instance, how quickly CRP levels fall after steroid use.

Keller also emphasized that the findings should in no way promote use of steroids in the outpatient setting for treating COVID-19.

Many physicians remain hesitant to use steroids because with other viruses such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and influenza "there were studies that showed that steroids could delay clearing the virus," she said.

Others are concerned about their potential to increase glucose or secondary bacterial or fungal infections.

An added benefit of the New York study is that 37.5% of patients studied were Black and 36% were Hispanic, groups that have been especially hard hit by COVID-19 but often underrepresented in research, Keller continued.

Randy Cron, MD, PhD, professor of medicine and pediatrics at University of Alabama at Birmingham (UAB), who is actively involved in COVID-19 research, told Medscape Medical News that UAB is among the institutions that have changed their thinking and moved toward promoting steroid use for certain hospitalized patients with COVID-19.

He said it's important to remember the New York report doesn't have the strength of a randomized trial, though it aligns with the findings of the RECOVERY trial.

But the findings about the CRP test may help clinicians make decisions for patients in the emergency room or admitted to the hospital with COVID-19 about whether to give steroids, he said.

The test is inexpensive, widely available, has a fast turnaround, and most patients with a fever entering the hospital would be getting it anyway, he noted.

Cron explained that what often kills patients with COVID-19 are the cytokine storms rather than the disease itself; the virus is what's triggering the cytokine storm.

Ideally, there would be treatment for both.

However, "At this point we don't have great antiviral therapy — remdesivir helps a little bit but it's not a home run," he noted.

The timing for giving steroids is also very important, he said.

"You don't necessarily want to give it really early on when the virus is going nuts because that's when giving immunosuppression, like a corticosteroid, is going to make it harder to keep the virus under control," he continued.

"But at the point where you're sick enough to be hospitalized with the coronavirus, that may be where you want to intervene to dampen down the immune system if it's up, and the C-reactive protein may be a marker of that."

He said the move toward steroid use for patients with COVID-19 strengthened as hospitals globally began to be overrun.

"Clinicians were tired of watching people die in front of them," he said. "People outside of clinical trials were using (steroids) in desperation and reporting, eventually, that they worked."

He explained there is still considerable hesitation to use steroids from conservative physicians who won't be convinced without more clinical trials.

On the other hand, he said, after the RECOVERY trial "some centers have completely flipped so that now everyone gets steroids and I'm not sure that's right either."

Ideally, there would be time for multiple randomized trials to help find the best solution.

"This isn't like we're exploring a new medicine for a chronic condition to see if it works better than something else. Hundreds of thousands of people have died and we don't necessarily have the time to wait for all these randomized trials. It's a tough question," he said.

Sobi provided study drugs for some COVID-19 trials at the University of Alabama at Birmingham. The study authors have disclosed no relevant financial relationships. Cron reported being a consultant for, receiving support from, or being on the advisory board for Novartis, Sobi, and Sironax.

J Hosp Med. Published online July 22, 2020. Full text

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.

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