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Blood test may identify which COVID-19 patients are best candidates for steroid treatment

A study led by Albert Einstein College of Medicine and Montefiore Health System confirms the findings of the large-scale British trial of steroid use for COVID-19 patients and advances the research by answering several key questions: Which patients are most likely to benefit from steroid therapy? Could some of them be harmed? Can other formulations of steroids substitute for the agent studied in the British trial?

The UK RECOVERY trial, a prospective, randomised, open-label study of the steroid dexamethasone versus standard of care, involved more than 6,000 patients with COVID-19. Dexamethasone reduced deaths by about one-third in patients on ventilators and by about one-fifth among people who needed oxygen but were not on ventilators. However, the study leaves questions about the use of steroids for treating some patients.

"Our study is consistent with the promising findings from Britain, but for the first time, we are able to demonstrate that people can see the same life-saving benefits with steroid formulations other than dexamethasone," said Dr Marla Keller, vice chair for research in the department of medicine at Einstein and Montefiore and lead author of the study. "We also found that a common blood test may identify the best candidates for steroid treatment." Keller is also professor of medicine and of obstetrics & gynaecology and women's health at Einstein and an infectious disease specialist at Montefiore.

Authors of the Einstein-Montefiore study compared outcomes for two groups selected from nearly 3,000 people hospitalised at Montefiore with a positive COVID-19 test. One group of 140 patients was treated with steroids within 48 hours of hospital admission; and a control group of 1,666 similar patients did not receive steroid therapy. Most of the patients who received steroid therapy received prednisone. Some received dexamethasone and methylprednisolone.

Nearly all patients initially had a blood test to measure levels of C-reactive protein (CRP), which the liver produces in response to inflammation. The higher the CRP level in the blood, the greater amount of inflammation. A normal CRP level reported in the study is below 0.8 milligrams per decilitre of blood.

"We found that in patients with high levels of inflammation, namely a CRP level greater than 20, steroids were associated with a 75% reduction in the risk of going on mechanical ventilation or dying," said Keller. "Critically, we also found that for patients with a normal or low level of inflammation, CRP levels less than 10, steroid use was associated with an almost 200% increased risk of going on mechanical ventilation or death."

A large percent of the people who succumb to COVID-19 die from the body's intense inflammatory response, which can overwhelm and severely damage the lungs. "Our findings suggest that steroid therapy should be reserved for people with high inflammation, as indicated by markedly elevated CRP levels," said Dr William Southern, professor of medicine and chief of the division of hospital medicine at Einstein and Montefiore and the study's senior author. "It's a different story for people who do not have significant inflammation: for them, any benefit is outweighed by the risks from using steroids."

Study co-author Dr Shitij Arora, associate professor of medicine at Einstein and a hospitalist at Montefiore, noted that the Einstein-Montefiore study included approximately equal numbers of male and female patients. In addition, nearly 40% of patients studied were Black and 36% were Hispanic. "The demographic diversity of the patients in this study suggests that steroid therapy benefits hospitalised COVID-19 patients affected by significant inflammation regardless of their race or ethnicity," he said.

The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.

Marla J Keller, Elizabeth A Kitsis, Shitij Arora, Jen-Ting Chen, Shivani Agarwal, Michael J Ross, Yaron Tomer, William Southern


[link url="https://www.einstein.yu.edu/news/2389/a-common-blood-test-identifies-which-covid-19-patients-benefit-and-which-are-harmed-from-steroid-treatment/"]Albert Einstein College of Medicine material[/link]


[link url="https://www.journalofhospitalmedicine.com/jhospmed/article/225402/hospital-medicine/effect-systemic-glucocorticoids-mortality-or-mechanical?channel=28090"]Journal of Hospital Medicine abstract[/link]

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