Treatment combos, ECMO outcomes, vaccine protection in COVID-19

Baricitinib plus remdesivir has similar outcomes to dexamethasone plus remdesivir in hospitalized patients with COVID-19 who require oxygen, but dexamethasone is associated with more adverse events, according to a recent randomized trial published May 23 by The Lancet Respiratory Medicine. Hospitalized adults (mean age, 58.3 years) who required supplemental oxygen via low-flow, high-flow, or noninvasive mechanical ventilation were randomly assigned to receive baricitinib, remdesivir, and placebo (n=516) or dexamethasone, remdesivir, and placebo (n=494). All patients received remdesivir for 10 or fewer days and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching IV placebo) for a maximum of 10 days.

The primary outcome, mechanical ventilation-free survival by day 29, was similar between the study groups (Kaplan-Meier estimates, 87.0% [95% CI, 83.7% to 89.6%] in the baricitinib group and 87.6% [95% CI, 84.2% to 90.3%] in the dexamethasone group; risk difference, 0.6 [95% CI, −3.6 to 4.8]; P=0.91). Thirty percent of the baricitinib group and 37% of the dexamethasone group had at least one adverse event (risk difference, 7.5% [95% CI, 1.6% to 13.3%]; P=0.014), while rates of treatment-related adverse events and severe or life-threatening adverse events were 4% and 10% (risk difference, 6.0% [95% CI, 2.8% to 9.3%]; P=0.00041) and 28% and 36% (risk difference, 7.7% [95% CI, 1.8% to 13.4%]; P=0.012), respectively.

The researchers concluded that adding baricitinib or dexamethasone to remdesivir yielded similar ventilation-free survival in hospitalized patients with COVID-19 on supplemental oxygen, adverse events were more commonly associated with dexamethasone. They said that choice of treatment can be individualized based on patients' side effect profile and comorbid conditions, ease of administration, and cost.

A systematic review and meta-analysis published May 23 by Critical Care found that outcomes of extracorporeal membrane oxygenation (ECMO) have worsened as the COVID-19 pandemic has progressed. Fifty-two studies of 18,211 patients published from Dec. 1, 2019, to Jan. 26, 2022, found a pooled mortality rate of 48.8% (95% CI, 44.8% to 52.9%; high-certainty evidence) in patients with COVID-19 requiring ECMO. Studies that enrolled patients later in the pandemic rather than earlier had higher mortality rates. Age, time of final patient enrollment from Jan. 1, 2020, proportion of patients receiving corticosteroids, and shorter time on ECMO were predictors of increased mortality. “It is evident that a one-size fits all protocolised approach to ECMO, used earlier in the pandemic, may not be as applicable as newer variants emerge, clinical patterns vary and management for severe COVID-19 changes,” the authors wrote. “Despite the increase in mortality over time, ECMO still serves an important role as supportive therapy for select patients. Physicians should carefully weigh the potential benefits and harms of ECMO for each patient in the context of resource availability, the individual's disease course, and local experience and mortality rates in order to decide on ECMO candidacy.”

Finally, a Canadian study published May 25 by Clinical Infectious Diseases matched 3,353 vaccinated patients hospitalized with COVID-19 with 16,711 unvaccinated patients between Jan. 1, 2021, and Jan. 5, 2022, and found that one, two, or three doses of a COVID-19 vaccine significantly reduced the risk of ICU admission and death, with adjusted odds ratios per additional dose of 0.66 (95% CI, 0.62 to 0.71) and 0.78 (95% CI, 0.72 to 0.84), respectively. “Even with diminished efficacy of vaccines against infection with novel [variants of concern], vaccines remain an important tool for reduction of ICU admission and mortality,” the authors concluded.