Key messages
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We are very confident that plasma from the blood of people who have recovered from COVID-19 (convalescent plasma) does not help people with moderate to severe COVID-19.
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Convalescent plasma may make little or no difference to people with mild COVID-19.
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We still need more evidence about people with mild COVID-19, those with no symptoms, and those with a weaker immune system.
What is convalescent plasma?
The body produces antibodies as one of its defences against infection. Antibodies are found in part of the blood called plasma. Plasma from people who have recovered from the COVID-19 virus contains COVID-19 antibodies. It can be used to make convalescent plasma, which is plasma that contains these antibodies.
Convalescent plasma has been used successfully to treat some viruses. This treatment (given by a drip or injection) is generally well-tolerated, but can cause unwanted effects.
What did we want to find out?
We wanted to find out whether convalescent plasma helps people with confirmed COVID-19. We looked at:
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deaths from any cause;
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worsening of people's condition, measured by the number of people who needed a ventilator (a machine that helps people breathe) or died;
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improvement in people's condition, measured by the number of people discharged from hospital;
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quality of life;
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unwanted effects.
What did we do?
We searched for studies that investigated convalescent plasma to treat people with COVID-19. Studies could take place anywhere in the world and include people with mild, moderate, or severe COVID-19.
Where possible, we combined the studies’ results to analyse them. We rated our confidence in the evidence, based on factors such as study methods and the number of people included.
What did we find?
We found 48 studies with 24,518 participants. Of these, 42 studies included people with moderate to severe COVID-19, and six studies included people with mild COVID-19. The following findings compare convalescent plasma with placebo (a 'dummy' treatment that does not contain any medicine but is given in the same way as the medicine being tested) or the standard care given to people with COVID-19.
People with moderate to severe COVID-19
In people with moderate to severe COVID-19, convalescent plasma:
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makes no difference to deaths from any cause up to 28 days after treatment. About 230 of 1000 people given placebo or standard care died, compared to 220 of 1000 people given convalescent plasma (31 studies, 20,798 people).
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makes little to no difference to needing support from a ventilator or dying. About 291 of 1000 people given placebo or standard care needed a ventilator or died, compared to 300 of 1000 people given convalescent plasma (8 studies, 15,189 people).
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makes no difference to people being discharged from hospital. About 670 of 1000 people in both groups were discharged from hospital (9 studies, 13,930 people).
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may result in no difference in people's quality of life (1 study, 483 people).
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probably makes no difference to serious unwanted effects. About 109 of 1000 people given placebo or standard care had serious unwanted effects, compared to 129 of 1000 people given convalescent plasma (11 studies, 5298 people).
People with mild COVID-19
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We are uncertain whether convalescent plasma reduces deaths from any cause up to 28 days after treatment. About 8 of 1000 people given placebo or standard care died, compared to 10 of 1000 people given convalescent plasma (3 studies, 1004 people).
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We are uncertain whether convalescent plasma reduces admission to hospital or death within 28 days after treatment. About 106 of 1000 people given placebo or standard care were admitted to hospital or died, compared to 48 of 1000 people given convalescent plasma (2 studies, 493 people).
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Convalescent plasma may result in no difference in the time until COVID-19 symptoms resolved (1 study, 376 people).
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None of the studies measured people's quality of life.
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We are uncertain whether convalescent plasma has an impact on serious unwanted effects. About 174 of 1000 people given placebo or standard care had serious unwanted effects, compared to 150 of 1000 people given convalescent plasma (2 studies, 494 people).
What are the limitations of the evidence?
For people with moderate to severe COVID-19, we are very confident in the evidence about the number of deaths from any cause, and whether people's condition worsened or improved, because the results are drawn from many high-quality studies with consistent results. We are only moderately confident about the evidence for serious unwanted effects because studies often reported these effects only for people treated with convalescent plasma, or did not report them.
For people with mild COVID-19, we have little to no confidence in the evidence because we could not identify enough consistent results from many of the studies.
We still have little evidence about quality of life and about the effects of convalescent plasma for people with mild disease.
How up to date is this evidence?
This updates our previous review published in 2023. The evidence is current to October 2024.
Read the full abstract
Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required.
Objectives
To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19.
Search strategy
To identify completed and ongoing studies, we searched CENTRAL, MEDLINE, Embase, the Epistemonikos COVID-19 L*OVE Platform, and clinical trial registries to October 2024.
Selection criteria
We included randomised controlled trials (RCTs) evaluating convalescent plasma for COVID-19, irrespective of disease severity, age, gender or ethnicity.
We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin.
Data collection and analysis
We followed standard Cochrane methodology.
To assess bias in included studies we used RoB 2. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality at up to day 28, worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life, grade 3 or 4 adverse events, and serious adverse events.
Main results
In this fourth review update version, we included 33RCTs with 24,861 participants, of whom 11,432 received convalescent plasma. Of these, nine studies are single-centre studies and 24 are multi-centre studies. Fourteen studies took place in America, eight in Europe, three in South-East Asia, two in Africa, two in western Pacific and three in eastern Mediterranean regions and one in multiple regions. We identified a further 49 ongoingstudies evaluating convalescent plasma, and 33 studies reporting as being completed.
Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease
29 RCTs investigated the use of convalescent plasma for 22,728 participants with moderate to severe disease. 23 RCTs with 22,020 participants compared convalescent plasma to placebo or standard care alone, five compared to standard plasma and one compared to human immunoglobulin. We evaluate subgroups on detection of antibodies detection, symptom onset, country income groups and several co-morbidities in the full text.
Convalescent plasma versus placebo or standard care alone
Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 220 per 1000; 21 RCTs, 19,021 participants; high-certainty evidence). It has little to no impact on need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.97 to 1.11; 296 per 1000; 6 RCTs, 14,477 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 665 per 1000; 6 RCTs, 12,721 participants; high-certainty evidence). Convalescent plasma may have little to no impact on quality of life (MD 1.00, 95% CI −2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). Convalescent plasma may have little to no impact on the risk of grades 3 and 4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 212 per 1000; 6 RCTs, 2392 participants; low-certainty evidence). It has probably little to no effect on the risk of serious adverse events (RR 1.14, 95% CI 0.91 to 1.44; 135 per 1000; 6 RCTs, 3901 participants; moderate-certainty evidence).
Convalescent plasma versus standard plasma
We are uncertain whether convalescent plasma reduces or increases all-cause mortality at up to day 28 (RR 0.73, 95% CI 0.45 to 1.19; 129 per 1000; 4 RCTs, 484 participants; very low-certainty evidence). We are uncertain whether convalescent plasma reduces or increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 311 per 1000; 1 study, 34 participants; very low-certainty evidence) and whether it reduces or increases the risk of serious adverse events (RR 0.80, 95% CI 0.55 to 1.15; 236 per 1000; 3 RCTs, 327 participants; very low-certainty evidence). We did not identify any study reporting other key outcomes.
Convalescent plasma versus human immunoglobulin
Convalescent plasma may have little to no effect on all-cause mortality at up to day 28 (RR 1.07, 95% CI 0.76 to 1.50; 464 per 1000; 1 study, 190 participants; low-certainty evidence). We did not identify any study reporting other key outcomes.
Individuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease
We identified two RCTs reporting on 536 participants, comparing convalescent plasma to placebo or standard care alone, and two RCTs reporting on 1597 participants with mild disease, comparing convalescent plasma to standard plasma.
Convalescent plasma versus placebo or standard care alone
We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (odds ratio (OR) 0.36, 95% CI 0.09 to 1.46; 8 per 1000; 2 RCTs, 536 participants; very low-certainty evidence). It may have little to no effect on admission to hospital or death within 28 days (RR 1.05, 95% CI 0.60 to 1.84; 117 per 1000; 1 RCT, 376 participants; low-certainty evidence), on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 483 per 1000; 1 RCT, 376 participants; low-certainty evidence), on the risk of grades 3 and 4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 144 per 1000; 1 RCT, 376 participants; low-certainty evidence) and the risk of serious adverse events (RR 1.14, 95% CI 0.66 to 1.94; 133 per 1000; 1 RCT, 376 participants; low-certainty evidence). We did not identify any study reporting other key outcomes.
Convalescent plasma versus standard plasma
We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (OR 0.30, 95% CI 0.05 to 1.75; 2 per 1000; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.49, 95% CI 0.31 to 0.75; 36 per 1000; 2 RCTs, 1595 participants; moderate-certainty evidence). Convalescent plasma may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.98 to 1.27; 1 RCT, 416 participants; low-certainty evidence). We did not identify any study reporting other key outcomes.
This is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence.
Authors' conclusions
Compared with placebo or standard care, high-certainty evidence shows that CP does not reduce mortality in individuals with moderate to severe disease and has little to no effect on clinical improvement or worsening. CP probably has little to no effect on serious adverse events. Publication of ongoing studies might resolve some of the uncertainties around CP therapy for people with asymptomatic or mild disease.
This review was previously a living systematic review, from the first version published in 2020 until our last search in October 2024. The research question is no longer a priority for decision-making, new studies are less frequently published, and research that might impact the conclusions of the review is no longer emerging.
Funding
The European Commission, Belgium SUPorting high quality evaluation of COVID‐19 convalescent plasma thrOughouT Europe (SUPPORT‐E, grant number 101015756) supported this review.
Registration
Protocol registered with the Center for Open Science on 17 April 2020 (DOI: 10.17605/OSF.IO/DWF53). Access the 2023 version of this review here: DOI: 10.1002/14651858.CD013600.pub6.
