麻豆传媒

Hospitalized patients with COVID-19 receiving convalescent plasma did not gain a statistically significant benefit in time to clinical improvement in a small randomized trial conducted in Wuhan, China.

But that may have been because the trial was stopped early, leaving it underpowered for many of the intended analyses.

Among the 103 patients treated in the study -- barely half of the originally planned 200 -- more patients receiving convalescent plasma in addition to standard treatment experienced clinical improvement within 28 days compare with a group getting standard care only (51.9% vs 43.1%, respectively; HR 1.40, 95% CI 0.79-2.49, P=0.26), reported Zhong Liu, MD, PhD, of Chinese Academy of Medical Sciences and Peking Union Medical College, and colleagues.

However, in a subgroup analysis of patients with severe, but not life-threatening, disease, there was a significant difference in clinical improvement in the plasma group compared to controls (HR 2.15, 95% CI 1.07-4.32, P=0.03), the authors wrote in JAMA.

Liu and colleagues explained that they had to give up enrolling patients in late March, when the outbreak in Wuhan petered out. Beginning March 24, no new cases were reported in the city where, just a few weeks earlier, hundreds were diagnosed every day. Had they succeeded in recruiting 200 patients, they estimated that the trial would have had 80% power to detect a benefit from the intervention.

The group recommended a new, larger trial of convalescent plasma in patients with severe COVID-19 where sufficient numbers can be enrolled.

Previously, a found beneficial effects of convalescent plasma among hospitalized COVID-19 patients, but an editorial warned .

In addition, Liu and colleagues noted its effects have been varied, likely due to "no standardization or evidence-based rationale for donor selection, quality control of convalescent plasma, or recipient transfusion indications for convalescent plasma."

They added the World Health Organization (WHO) issued guidelines advocating for standardization and quality control in convalescent plasma use, and the FDA recently approved emergency use of convalescent plasma in patients with severe COVID-19, though "the evidence supporting its use ... remains limited, and thus its use remains investigational."

This open-label trial from seven medical centers in Wuhan randomized patients with "severe" COVID-19 (respiratory distress and/or hypoxemia) or "life-threatening" COVID-19 (shock, organ failure, or requiring mechanical ventilation) to standard care with or without infusions of plasma taken from patients with previous known SARS-CoV-2 infection in the recovery stage.

Primary outcome was time to clinical improvement, defined as either discharge from the hospital or a reduction of 2 points on a 6-point disease severity scale.

Overall, 52 patients were randomized to receive convalescent plasma in addition to standard care, and 51 received standard care only. Of these, 23 patients in the plasma group and 22 in the control group had severe COVID-19, while 29 patients in both groups had life-threatening disease.

Median age was 70 years, and about 60% were men, with a median interval from onset of symptoms to randomization of 30 days.

Among those with severe disease, the primary outcome occurred in 91.3% of the plasma group and 68.2% of controls. However, among those with life-threatening disease, the difference between groups was non-significant (HR 0.88, 95% CI 0.30-2.63, P=0.83).

Differences in 28-day mortality or time from randomization to discharge did not reach significance either, but did trend in favor of the intervention. Additionally, rates of conversion to negative SARS-CoV-2 viral PCR in the convalescent plasma group were significantly higher than controls at 24, 48, and 72 hours. At that final point, convalescent plasma was associated with conversion among 87.2% of participants versus 37.5% of controls.

An by Arturo Casadevall, MD, PhD, of Johns Hopkins Bloomberg School of Public Health, and colleagues noted the positive trends and echoed the call for additional study. They also highlighted the apparent lack of any benefit in the "life-threatened" group, which suggests (along with findings from studies of other interventions) that once patients reach the stage of needing mechanical ventilation, they may be beyond help.

New, larger trials should answer many of the questions the truncated study by Liu and colleagues left hanging, the editorialists said.

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