Early convalescent plasma infusion does not prevent COVID-19 progression

An infusion of convalescent plasma, obtained via blood donation from individuals who have recovered from COVID-19, did not prevent disease progression in high-risk outpatients who presented within 7 days of COVID-19 symptom onset, results of the phase III US-based SIREN-C3PO* study showed.

Participants in this multicentre, single-blind trial were 511 adults aged ≥50 years or with ≥1 risk factor for disease progression (median age 54 years, 54 percent female) who presented at emergency departments within 7 days (median 4 days) of experiencing COVID-19 symptoms. The cohort was limited to patients who were in stable condition and were candidates for outpatient management (not requiring supplemental oxygen). They were randomized 1:1 to receive a single unit of ABO-compatible convalescent plasma containing a high titre of SARS-CoV-2 neutralizing antibodies (median 1:641) or placebo.

Disease progression – any-cause hospitalization, requirement of emergency or urgent care, or death without hospitalization – within 15 days of randomization did not significantly differ between patients assigned to convalescent plasma and placebo (30.0 percent vs 31.9 percent; risk difference, 1.9 percentage points, 95 percent credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68 [>0.999 defined as evidence of superiority]).

After excluding the 25 patients who were hospitalized during the index visit (19 and six in the convalescent plasma and placebo groups, respectively), the posterior probability of superiority of convalescent plasma in the intention-to-treat population was 0.93.

When examined separately, any-cause hospitalization was comparable between the convalescent plasma and placebo groups (19.8 percent vs 22.0 percent), as was seeking of emergency or urgent care (9.7 percent vs 9.8 percent). There was one death without hospitalization in the convalescent plasma and none in the placebo group.

Six deaths occurred within 30 days, five and one in the convalescent plasma and placebo group, respectively (risk difference, -1.6 percentage points), with none deemed related to trial medications.

Worst severity of illness within 30 days based on an 8-category ordinal scale score was comparable between groups, as was number of hospital-free days over the trial period (mean 28.3 vs 28.6 days). 

Worsening of symptoms within 15 days of randomization based on the 5-category outpatient scale occurred in 41.6 and 45.7 percent of convalescent plasma and placebo recipients, respectively, with time until worsening of symptoms similar between groups (hazard ratio, 0.90).

Adverse event incidence was comparable between groups. Dyspnoea occurred more often with placebo. Infusion-related reactions occurred more often with convalescent plasma, with three of these considered serious and warranting glucocorticoid or epinephrine administration or hospitalization.

Convalescent plasma for COVID-19: Yes or no?

“The results show that convalescent plasma does not appear to benefit this particular group,” said study co-author Dr Nahed El Kassar from the National Heart, Lung, and Blood Institute, Bethesda, Maryland, US.

“We were hoping that the use of COVID-19 convalescent plasma would achieve at least a 10 percent reduction in disease progression in this group, but instead the reduction we observed was less than 2 percent,” added principal investigator Professor Clifton Callaway from the University of Pittsburgh, Pittsburgh, Pennsylvania, US. “[W]e wanted this to make a big difference in reducing severe illness and it did not.”

However, the authors did not discount the potential use of convalescent plasma altogether. “Convalescent plasma may still play a role if it is administered before the development of native antibodies. The treatment may also be efficacious in preventing symptomatic COVID-19 after exposure,” they said.

Highlighting that studies are still being done on the effectiveness of convalescent plasma for COVID-19, they recommended that researchers investigate whether the therapeutic effect of this treatment differs based on geographic location or timing of plasma collection.

In this study, timing of treatment and insufficient plasma dose or neutralizing antibody titres could have been reasons for failure. “[H]ost factors and other aspects of the host response to the infection may be more important than humoral immunity for determining the natural history of the illness,” they concluded.