Convalescent plasma has been utilised for over a century as passive immunotherapy for influenza pneumonia, and even more lately for SARS-CoV-1. Although retrospective studies indicate it may minimise mortality in serious viral respiratory infections, the evidence from randomised trials is scarce and highly questionable.

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Usage of convalescent plasma

Other than clinical studies, convalescent plasma has been used by more than thousands of patients in the US Food and Drug Administration's (FDA) Expanded Access Program. A retrospective (non-randomised) study of 3082 patients who received convalescent plasma as a part of the program showed that 30-day mortality was reduced among those who did not require mechanical ventilation until administering higher-titre plasma (containing higher amounts of anti-SARS-CoV-2 spike IgG) compared to those who received lower-titre plasma.

There have been a few randomised studies of convalescent plasma in COVID-19 patients, but they have all been limited and unclear. Furthermore, since COVID-19 patients are diverse, the advantage of convalescent plasma could be restricted to those with relatively mild disease, those who are still in the early stages of their infection, or those who have not mounted an adequate antibody response. As a result, the effectiveness of convalescent plasma as a therapy for COVID-19-infected patients is still unclear.

RECOVERY trial

High-titre convalescent plasma did not enhance longevity or other predefined clinical results in the RECOVERY study and the first clinical trial of convalescent plasma on any infectious indication.

Convalescent plasma did not increase survival or other clinical outcomes in hospitalised patients with COVID-19, according to the findings of this major, randomised study. Age, sex, race, period of symptoms before randomisation, degree of breathing therapy obtained at randomisation, and use of corticosteroids all had similar outcomes.

There have been nine further randomised trials of convalescent plasma for the treatment of COVID-19-infected hospitalised patients, with a total of fewer than 200 fatalities. None of these studies has shown that convalescent plasma has a favourable impact on mortality.

When all trial outcomes are assessed, including RECOVERY (which is more than ten times higher than all other trials combined), allocation to convalescent plasma does not reduce fatalities (mortality RR 0•99, 95 per cent CI 0•92–1•06, p=0•77).

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