Death benefit not seen in patients on mechanical ventilation

Among patients hospitalized with Covid-19 not receiving mechanical ventilation, treatment with high-titer convalescent plasma was associated with a lower risk for death than those receiving plasma with low antibody, according to peer-reviewed findings from a retrospective analysis of more than 3,000 patients.

In addition, patients who received convalescent plasma very early – within 3 days of receiving a diagnosis of Covid-19 – had a lower risk of death than those who received the treatment later in the disease course.

Findings from the study of patients enrolled in the Mayo Clinic’s Covid-19 Convalescent Plasma Extended-Access Program were published ahead of peer review in mid-August, and they were instrumental in the decision by the U.S. Food and Drug Administration to grant emergency-use authorization (EUA) status for convalescent plasma for the treatment of adults hospitalized with Covid-19.

The peer-reviewed study findings were published online January 13 in New England Journal of Medicine.

“These data show that the benefit of convalescent plasma was most apparent in patients who received plasma transfusions containing higher levels of anti-SARS-CoV-2 IgG antibodies early in the disease course,” wrote lead researcher Michael J. Joyner, MD, of Mayo Clinic, Rochester, Minnesota.

Earlier this month, findings from a pivotal randomized trial of convalescent plasma showed high-titer plasma to be associated with improved outcomes very early in the course of Covid-19.

Early administration of high-titer convalescent plasma was associated with reduced progression to severe Covid-19 in older adults treated within 72 hours of mild symptom onset in the INFANT-Covid-19 trial.

Among older patients with SARS-CoV-2 infection and recent symptoms onset, treatment with high titer convalescent plasma was associated with a 48% reduction in the risk of progression to severe respiratory disease.

The trial, which was conducted in Argentina from June to Oct. 2020, was stopped early at 76% of projected accrual due to declines in community spread of Covid-19, which slowed recruitment.

In an editorial published with the study by Joyner and colleagues, infectious disease specialist Louis M. Katz, MD, of the Mississippi Valley Regional Blood Center, Davenport, Iowa, described the supply of convalescent plasma last fall in the U.S. as “tenuous,” due to the spike in cases, while noting that more recent collections have improved.

He wrote that if collections are restricted to high-antibody titers “the supply of convalescent plasma will be stressed,” noting that at his center, only around 1 in 5 donations involve high IgG antibody plasma.

“Shifting the pool of potential recipients away from those included in the EUA to the many infected outpatients whose risk of hospitalization and eventual need for advanced care cannot be precisely estimated should lead to the extension of convalescent plasma transfusions to pre-hospital venues (although this is not yet permitted in the EUA),” Katz wrote.

Katz added that “uncontrolled compassionate use of convalescent plasma in patients other than those with an early infection that is likely to progress to more severe illness should be discouraged, even though clinicians recognize how difficult it can be to ’just stand there’ at the bedside of a patient in the ICU.”

The retrospective analysis by Joyner and colleagues included data on 3,082 patients who received convalescent plasma at one of 680 acute care facilities across the U.S. prior to July 5 of 2020. Roughly 2 out of 3 patients (69%) were younger than age 70.

Convalescent plasma IgG antibody levels were categorized as low (<4.62), medium (4.62-18.45) or high >18.45), with 561, 2,006 and 515 patients, respectively, receiving low, medium and high titer plasma.

The three groups were generally similar in terms of demographic characteristics, risk factors associated with severe Covid-19, and concomitant use of other therapies for Covid-19.

Death within 30 days of plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2,006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group.

A lower risk for death within 30 days in the high-titer group than in the low-titer group was seen among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% CI, 0.48-0.91) and no effect on death risk was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78-1.32).

“Although patient age was not the primary focus of these analyses, it was estimated to be the most important variable in predicting the risk of death within 30 days after plasma transfusion,” the researchers wrote. “The next two most important correlates of this risk — receipt of invasive mechanical ventilation and admission to the ICU — occur late in the course of the disease, when the level of antibodies in the transfused plasma does not appear to affect the risk of death.”

  1. Among patients hospitalized with Covid-19 not receiving mechanical ventilation, treatment with high-titer convalescent plasma was associated with a lower risk for death than those receiving plasma with low antibody.
  2. Patients who received convalescent plasma very early — within 3 days of receiving a diagnosis of Covid-19 — had a lower risk of death than those who received the treatment later in the disease course.

Salynn Boyles, Contributing Writer, BreakingMED™

This research was funded by the Department of Health and Human Services.

 

Cat ID: 190

Topic ID: 79,190,254,930,791,932,190,926,192,927,151,928,925,934