Infectious Disease

Convalescent plasma lowers 28-day mortality in COVID-19-induced ARDS

October 25, 2023

4 min read

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Key takeaways:

  • Fewer patients with COVID-19-induced ARDS who received convalescent plasma vs. standard care after ventilation died at day 28.
  • Mortality between groups changed based on time on ventilation before treatment.

Treatment with convalescent plasma reduced 28-day mortality among adults undergoing mechanical ventilation for COVID-19-induced acute respiratory distress syndrome, according to results published in The New England Journal of Medicine.

Results, which were published in conjunction with a presentation at this year’s European Society of Intensive Care Medicine meeting in Milan, showed this effect was more pronounced among those randomized within 48 hours of mechanical ventilation initiation.

Data were derived from Misset B, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2209502.

Benoît Misset

“The pandemic was a particular opportunity to conduct trials on large and homogeneous populations,” Benoît Misset, MD, of the department of intensive care medicine at University Hospital in Liege, Belgium, told Healio. “Concerning ARDS, our results reinforce the adage according to which the treatment of ARDS, in addition to sophisticated ventilatory assistance, is a treatment of its cause, at least when such a treatment (here plasma) exists.

“Although convalescent plasma has long been advocated to cure certain severe infectious diseases, this had never really been supported by well-conducted trials on large populations,” Misset added. “Our trial supports the fact that convalescent plasma could be useful in certain infectious diseases for which antimicrobial drugs are not, or not yet, effective.”

In an open-label trial, Misset and colleagues evaluated 475 adults with COVID-19-induced ARDS between September 2020 and March 2022 placed on mechanical ventilation for less than 5 days to determine the impact of convalescent plasma treatment on 28-day mortality.

Of the total cohort, 237 patients (median age, 64 years; 66.7% men) received convalescent plasma, whereas 238 patients (median age, 64 years; 69.3% men) received only standard care. Nearly all of the population (98.1%) received glucocorticoids.

Notably, 17.7% of those in the treatment group received convalescent plasma with a neutralizing antibody titer of 1:160 because of a shortage, researchers reported. The remaining patients from this group received plasma with either a neutralizing antibody titer of 1:320 (38.8%), 1:640 (31.9%) or greater than 1:640 (11.6%).


Researchers observed fewer deaths in the convalescent plasma group at day 28 compared with the standard care group (35.4% vs. 45%; P = .03), with the survival curves starting to show separation at day 17.

Additionally, when split according to time on mechanical ventilation before randomization, researchers observed a greater difference in mortality between the two groups during analysis of patients who underwent randomization within 48 hours of being mechanically ventilated (convalescent plasma, 32.7% vs. standard care, 46.8%) vs. after 48 hours (42.4% vs. 40.3%).

There was no link between neutralizing antibody titer and mortality, according to researchers.

A total of 711 adverse events occurred in this study, including 209 serious adverse events, of which 184 were fatal. More patients from the standard care group vs. the convalescent plasma group experienced an adverse event (387 vs. 324), a serious adverse event (116 vs. 93) and a fatal serious adverse event (106 vs. 78).

Researchers indicated that most adverse events were related to COVID-19 or its complications and none could be directly attributed to the study treatment.

Secondary bacteremia prevalence, ventilator-associated pneumonia prevalence, organ support duration and hospital length of stay appeared comparable between the two groups.

Patients from both groups also showed higher mean neutralizing antibody and total IgG titers to SARS-CoV-2.

Future studies

Reflecting on this study and its findings, Misset told Healio that this patient population is no longer being observed.

“Indeed, the current variants of the virus are no longer responsible for a disease as serious as that which we encountered in 2020 to 2022, namely COVID-19 pneumonia with criteria for ARDS in immunocompetent patients,” Misset said. “It is therefore difficult to recommend the treatment that we tested on a specific population.”

Misset further told Healio that their trial is a poor representation of the current group of patients who are difficult to treat, which includes patients who are immunocompromised, do not need mechanical ventilation and are contracting COVID-19 along with other acute pathologies or risk factors of ARDS.

“The impact of our trial is therefore limited by these aspects, but we are still learning lessons from this pandemic, and the fact that trials conducted during a pandemic are not directly applicable afterwards may be a characteristic of acute infectious disease pandemics,” he said. “We believe health systems should consider collecting plasma from current COVID-19 patients, testing them for neutralization and deciding with experts whether certain patients with particular severity should receive highly neutralizing plasma.”

When asked about future trials, Misset suggested focusing on three separate points.

“First, when designing a trial in intensive care patients with the ambition to reduce mortality, it is necessary to choose a population with strict inclusion criteria (which we did) or to stratify randomization according to severity criteria (in particular, invasive mechanical ventilation is a solid and objective criterion) — if the large platforms which carried out the trials on thousands of patients had done so, their results would have been either different or more decisive for this same population,” Misset told Healio.

Misset’s second point addresses the say regulatory agencies have in trials.

“Regulatory agencies should not decide to allow compassionate use under public pressure without knowing anything about the effectiveness of the treatment. Unfortunately, this led to the termination of very good trials in the United States, which would have answered the question earlier than expected,” he said.

Lastly, Misset brought up an issue concerning exclusion criteria based on this trial and others conducted in critically ill patients.

“Experts should not recommend excluding a population from trials on the grounds that patients are too seriously ill,” he said. “In the situation that interests us, patients in intensive care, once invasively ventilated, were considered too ill or too late to benefit, and excluded from most trials. However, these were patients for whom intensive care doctors were fighting, who occupied most of the intensive care beds on the planet and who had a high mortality rate. But they also had good potential for ad integrum recovery. From a statistical point of view, the fact that mortality was around 50% even offered good potential to demonstrate a reduction in mortality if the treatment was effective.”



Misset reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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