Recent research looks at remdesivir, steroids, biomarkers for COVID-19

Results from two trials of remdesivir were published by the New England Journal of Medicine. The first study, published May 22, expanded on data released in an April 29 press release from the NIH. The trial, which included 1,059 hospitalized patients before it was halted, showed a significantly faster median recovery time of 11 days in the 538 patients randomized to remdesivir versus 15 days in the 521 patients in the placebo group. Mortality rates at 14 days were not significantly different (7.1% vs. 11.9%). The second study, which was industry-funded and published May 27, compared five versus 10 days of remdesivir in 397 hospitalized patients and found no significant difference between groups. Based on these results and the limited availability of the drug, an accompanying editorial recommended that “priority should be given to a 5-day remdesivir regimen for patients at the early stages of severe disease (i.e., when they are receiving supplemental oxygen but have not yet been intubated), since the evidence for benefit is clearest in this population.”

Another study, published by Clinical Infectious Diseases on May 19, found potential benefit from an early, short course of methylprednisolone in patients with moderate to severe COVID-19. The pre-test, single post-test, quasi-experiment included 213 patients treated in a Michigan health system. The 132 patients who got methylprednisolone, 0.5 to 1 mg/kg per day in two IV doses for three days, had a significantly lower rate of the composite endpoint of escalation from ward to ICU care, new requirement for mechanical ventilation, and mortality (34.9% vs. 54.3%; P=0.005) as well as shorter length of stay. The authors noted that corticosteroids are not routinely recommended in patients with COVID-19 and that the data on this question have been conflicting, but they believe that if given early, steroids “may attenuate progression to the hyper-inflammation phase that requires escalation of care.”

Two studies identified biomarkers, including C-reactive protein (CRP), which may predict critical illness from COVID-19. The first, published by Clinical Infectious Diseases on May 23, included 298 hospitalized Chinese patients, 84 of whom died. Age, neutrophil count, platelet count, and CRP level were all predictors of adverse outcomes, but CRP was the best, with levels at admission predicting both mortality and critical illness. “Patients with markedly elevated admission CRP should be provided more attention and strengthened treatment,” the study authors said. The other study, published by The BMJ on May 22, included 5,279 New York patients with COVID-19, 2,741 of whom were hospitalized. Predictors of critical illness included admission oxygen saturation less than 88%, troponin level greater than 1 ng/mL, CRP level greater than 200 mg/dL, and D-dimer level greater than 2,500 ng/mL. The association between inflammatory markers and mortality and critical illness was “striking,” and thus measurement of these markers should be routinely considered by clinicians, the authors said. Another significant finding was that the risk of critical illness decreased over the study period, which “raises the possibility that familiarity with the disease, ongoing iteration of protocols and practices in response to observed outcomes, and initiation of new treatments might improve outcomes even in the absence of vaccination or regimens known to be effective,” they wrote.

In some additional good news, an open-label, manufacturer-funded trial of a vaccine that included 108 participants in China found that it was “tolerable and immunogenic,” according to results published by The Lancet on May 22.

Finally, on May 23, the CDC offered interim guidance on the use of antibody testing, including that clinicians should reduce the risk of false-positive results by “choosing an assay with high specificity and by testing populations and individuals with an elevated likelihood of previous exposure.”