Covid-19 living Data

Pharmacologic treatments for covid-19 patients

Convalescent plasma vs Standard care/Placebo

This comparison will not be updated. Last search date 14 Dec, 2022.

Studies included but not extracted/included in the analysis: Jalili E,Tanaffos, 2022; Denkinger C M, medrxiv, 2022 ; Thorlacius-Ussing L, Sci Rep, 2022; Villanueva C, medrxiv, 2022 ; Muller-Tidow C, Hemasphere, 2022

Outpatients

Forest plots
(last update: 2022-11-17)

Summary of findings
(last update: 2022-11-24)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Convalescent plasma
Comparison: Standard care/Placebo

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 1.08 (0.80 - 1.45)	14 more per 1000 (from 35 fewer to 78 more)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Multicentre study conducted across several countries, therefore not downgraded for indirectness Imprecision: Serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect/trivial effect
1 trials Millat-Martinez P, 2022 797 participants		Convalescent plasma 187 per 1,000 (138 - 251)	Standard care/Placebo 173 per 1,000
Clinical improvement D60	Outcome not yet measured or reported
Hospitalisation or death	RR: 0.82 (0.66 - 1.02)	20 fewer per 1000 (from 38 fewer to 2 more)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to low number of participants/events
4 trials Millat-Martinez P, 2021; Sullivan D, 2021; Korley F, 2021; Alemany A, 2022 2909 participants		Convalescent plasma 91 per 1,000 (73 - 113)	Standard care/Placebo 111 per 1,000
WHO progression score (level 7 or above) D28	RR: 0.79 (0.17 - 3.62)	2 fewer per 1000 (from 8 fewer to 25 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Serious Inconsistency downgraded by 1 level: I²=:57.4% Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for no effect/trivial effect and the possibility for harm
3 trials Millat-Martinez P, 2021; Sullivan D, 2021; Korley F, 2021 2533 participants		Convalescent plasma 7 per 1,000 (2 - 34)	Standard care/Placebo 9 per 1,000
WHO progression score (level 7 or above) D60	RR: 0.50 (0.09 - 2.70)	11 fewer per 1000 (from 19 fewer to 36 more)		Very low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
1 trials Alemany A, 2022 376 participants		Convalescent plasma 11 per 1,000 (2 - 57)	Standard care/Placebo 21 per 1,000
All-cause mortality D28	RR: 0.85 (0.11 - 6.57)	1 fewer per 1000 (from 4 fewer to 26 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Serious Inconsistency downgraded by 1 level: I²=:51.3% Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for no effect/trivial effect and the possibility for harm
3 trials Millat-Martinez P, 2021; Sullivan D, 2021; Korley F, 2021 2533 participants		Convalescent plasma 4 per 1,000 (1 - 31)	Standard care/Placebo 5 per 1,000
All-cause mortality D60	RR: 0.17 (0.02 - 1.41)	5 fewer per 1000 (from 6 fewer to 3 more)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to low number of participants/events
2 trials Alemany A, 2022; Sullivan D, 2021 1601 participants		Convalescent plasma 1 per 1,000 (0 - 9)	Standard care/Placebo 6 per 1,000
Viral negative conversion D7	RR: 1.00 (0.61 - 1.64)	0 fewer per 1000 (from 56 fewer to 92 more)		Very low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
1 trials Alemany A, 2022 376 participants		Convalescent plasma 144 per 1,000 (88 - 236)	Standard care/Placebo 144 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
Adverse events	RR: 1.32 (0.28 - 6.15)	25 more per 1000 (from 56 fewer to 404 more)		Very low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Very serious Inconsistency downgraded by 2 levels: I²=:91.9% Indirectness: Not serious We presume that the adverse event rates and the corresponding relative risks, are similar across diverse settings, therefore not downgraded for indirectness Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
2 trials Sullivan D, 2021; Alemany A, 2022 1601 participants		Convalescent plasma 104 per 1,000 (22 - 483)	Standard care/Placebo 78 per 1,000
Serious adverse events	RR: 0.94 (0.73 - 1.22)	5 fewer per 1000 (from 24 fewer to 20 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
3 trials Sullivan D, 2021; Alemany A, 2022; Korley F, 2021 2112 participants		Convalescent plasma 84 per 1,000 (66 - 110)	Standard care/Placebo 90 per 1,000

¹The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Hospitalized patients

Forest plots
(last update: 2022-10-20)

Funnel plots
(last update: 2022-10-08)

Summary of findings
(last update: 2022-10-23)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Convalescent plasma
Comparison: Standard care/Placebo

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 1.00 (0.98 - 1.02)	0 fewer per 1000 (from 13 fewer to 13 more)		High certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns regarding adequate randomization, deviation from intended intervention, missing data, outcome measurement and selection of reported results, not downgraded for risk of bias beacause the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Not serious
15 trials NCT04539275 2022;Lacombe K, 2022; Bar KJ, 2021; Rojas M, 2022; Bajpai M, 2022; van den Berg K, Ortigoza MB, 2021; 2022; Self WH, 2022; Horby P, 2021; Song ATW, 2022; Sekine L, 2021; Gharbharan A, 2021; Simonovich VA, 2020; Li L, 2020; AlQahtani M, 2021 15204 participants		Convalescent plasma 655 per 1,000 (642 - 668)	Standard care/Placebo 655 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
Clinical improvement D60	RR: 1.25 (1.02 - 1.53)	186 more per 1000 (from 15 more to 394 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect/trivial effect
1 trials Bar KJ, 2021 80 participants		Convalescent plasma 929 per 1,000 (758 - 1000)	Standard care/Placebo 744 per 1,000
WHO progression score (level 7 or above) D28	RR: 1.06 (0.94 - 1.19)	11 more per 1000 (from 11 fewer to 34 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns with deviation from intended intervention and selection of the reported results, not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
11 trials Libster R, 2021; Avendaño-Solà C, 2020; NCT04539275 2022; Lacombe K, 2022; Bajpain M, 2022; Ortigoza MB, 2021; Menichetti F, 2021; Simonovich VA, 2020; Begin P, 2021; Sekine L, 2021; Self WH, 2022 4941 participants		Convalescent plasma 190 per 1,000 (169 - 213)	Standard care/Placebo 179 per 1,000
WHO progression score (level 7 or above) D60	RR: 0.65 (0.35 - 1.19)	85 fewer per 1000 (from 157 fewer to 46 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns with adequate randomosation deviation from intended intervention missing data and selection of the reported results, not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
2 trials Pouladzadeh M, 2021; Lacombe K, 2022 182 participants		Convalescent plasma 157 per 1,000 (85 - 288)	Standard care/Placebo 242 per 1,000
All-cause mortality D28	RR: 0.98 (0.93 - 1.03)	5 fewer per 1000 (from 16 fewer to 7 more)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Despite concerns regarding adequate randomisation, deviation from intended intervention, missing data and selection of reported results, not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect/trivial effect
29 trials Libster R, 2021; Avendaño-Solà C, 2021; NCT04539275 2022; Lacombe K, 2022; Devos T, 2021; Bar KJ, 2021; Kirenga B, 2021; Agarwal A, 2020; Rojas M, 2022; Bargay-Lleonart J, 2022; Bajpai M, 2022; van den Berg K, 2022; Ortigoza MB, 2021; Menichetti F, 2021; Begin P, 2021; Self WH, 2022; Koerper S, 2021; Horby P, 2021; Fernandez-Sanche z V, 2022; Holm K, 2021; Sekine L, 2021; Ray Y, 2022; Simonovich VA, 2020; Al Qantani M, 2021; NCT04385199 2022; de Santis GC, 2022; Estcourt L, 2021; Li L, 2020; Baldeon ME, 2022 20629 participants		Convalescent plasma 222 per 1,000 (211 - 233)	Standard care/Placebo 227 per 1,000
All-cause mortality D60	RR: 0.74 (0.53 - 1.04)	650 fewer per 1000 (from 1175 fewer to 100 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level:due to some concerns with adequate randomisation, deviation from intended intervention, missing data and selection of reported results Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
7 trials Lacombe K, 2022; Bar KJ, 2021; Pouladzadeh M, 2021; Koerper S, 2021; Gharbharan A, 2021; Begin P, 2021; De Santis GC, 2022 1503 participants		Convalescent plasma 1851 per 1,000 (1325 - 1000)	Standard care/Placebo 2501 per 1,000
Viral negative conversion D7	RR: 1.25 (0.94 - 1.67)	68 more per 1000 (from 16 fewer to 183 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding adequate randomization, deviation from intended intervention, missing data and selection of the reported result Inconsistency: Serious Inconsistency downgraded by 1 level: I²=67.6% Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect/trivial effect
7 trials Bar KJ, 2021; Agarwal A, 2020; Sekine L, 2021; Li L, 2020; Salman OH, 2020; Kirenga B, 2021; Ortigoza MB, 2021 1465 participants		Convalescent plasma 342 per 1,000 (257 - 457)	Standard care/Placebo 273 per 1,000	2 additional studies were identified that assessed this outcome, but no results were reported.
Adverse events	RR: 1.08 (0.99 - 1.18)	14 more per 1000 (from 2 fewer to 33 more)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns regarding deviation from intended intervention, missind data, outcome measurement, and selection of the reported results not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to low number of participants/events
15 trials Libster R, 2021; Lacombe K, 2022; Bar KJ, 2021; Kirenga B, 2021; Rojas M, 2022; Bargay-Lleonart J, 2022; van den Berg K, 2022; Ortigoza MB, 2021; Menichetti F, 2021; Self WH, 2022; Koerper S, 2021; Holm K, 2021; Sekine L, 2021; Simonovich VA, 2020; Li L, 2020 3892 participants		Convalescent plasma 196 per 1,000 (179 - 214)	Standard care/Placebo 181 per 1,000
Serious adverse events	RR: 1.11 (1.00 - 1.23)	15 more per 1000 (from 0 fewer to 31 more)		Low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding adequate randomization, deviation from intended intervention, missing data, outcome measurement and selection of reported results Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for no effect/trivial effect and the possibility for harm
20 trials Libster R, 2020; Avendaño-Solà C, 2020; NCT04539275 2022; Lacombe K, 2022; Devos T, 2021; Bar KJ, 2021; Rojas M, 2022; Bargay-Lleoart J, 2022; van den Berg K, 2022; Ortigoza MB, 2021; Begin P, 2021; Self WH, 2022; Koerper S, 2021; Holm K, 2021; Sekine L, 2021; Gharbharan A, 2020; Simonovich VA, 2020; NCT04385199 2022; Estcourt L, 2021; Li L, 2020 7239 participants		Convalescent plasma 151 per 1,000 (136 - 167)	Standard care/Placebo 136 per 1,000

¹The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)

CI: Confidence interval; RR: Risk ratio

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Permanent URL for this comparison: https://covid-nma.com/living_data/index.php?comparison=22

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Trial	Funding	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Treatment 1	Treatment 2
NCT04385199 NCT04385199, Unpublished, 2022 Full text	Not reported/unclear	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (severe-critical) admitted to a single center in the USA.	N=30	Some concerns Details	Full description
NCT04429854 DAWN-plasma trial Devos T, Eur Respir J, 2021 Full text Commentary	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (mild-severe) admitted to 22 centers in Belgium	N=489	Some concerns Details	Full description
NCT04539275 VACURES-1 NCT04539275, Unpublished, 2022 Full text	Not reported/unclear	Convalescent plasma	Placebo	RCT	Patients with confirmed COVID-19 (moderate) admitted to 24 centers in the USA.	N=75	Some concerns Details	Full description
NCT04345991 CORIPLASM Lacombe K, Vox Sang, 2022 Full text	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (moderate) admitted to 14 centers in France.	N=120	Some concerns Details	Full description
NCT04362176 PassITON Self WH, Chest, 2022 Full text Commentary	Public/non profit	Convalescent plasma	Placebo	RCT	Patients with confirmed COVID-19 (mild-critical) admitted to 25 centers in USA.	N=974	Low Details	Full description
NCT04332835 Rojas M, BMC Infect Dis, 2022 Full text Commentary	Mixed	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to three centers in Colombia	N=101	Some concerns Details	Full description
NCT04803370 Bargay-Lleonart J, J Clin Med, 2022 Full text Commentary Commentary	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to 3 hospitals in Spain.	N=55	Some concerns Details	Full description
NCT04425915 COPLA-II trial Bajpai M, BMJ Open, 2022 Full text Commentary Commentary	No specific funding	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to 2 centers in India.	N=400	Some concerns Details	Full description
NCT04405310 Fernandez-Sanchez V, Research Square, 2022 Full text Commentary Commentary	Public/non profit	Convalescent plasma	Placebo	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to two centers in Mexico	N=43	Some concerns Details	Full description
NCT04415086 COOP-COVID-19-MCTI Song ATW, Lancet Reg Health Am, 2022 Full text Commentary	Public/non profit	Convalescent plasma -High volume	Convalescent plasma -Low volume	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to 7 centers in Brazil.	N=129	Some concerns Details	Full description
NCT04621123 Alemany A, Lancet Respir Med, 2022 Full text Commentary Commentary	Mixed	Convalescent plasma	Placebo	RCT	Outpatients with confirmed COVID-19 (mild-moderate) treated at 4 centers in Spain.	N=376	Low Details	Full description
NCT04516811 PROTECT-Patient van den Berg K, Sci Rep, 2022 Full text Commentary Commentary	Public/non profit	Convalescent plasma	Placebo	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to 4 centers in South Africa.	N=103	Low Details	Full description
RBR-7f4mt9f De Santis GC, Emerg Infect Dis, 2022 Full text Commentary	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (severe-critical) admitted to 5 centers in Brazil	N=110	Some concerns Details	Full description
ISRCTN85216856 Baldeon ME, Transfus Med, 2022 Full text Commentary	Public/non profit	Convalescent plasma	Placebo	RCT	Patients with suspected or confirmed COVID-19 (unclear severity) admitted to 3 centers in Ecuador.	N=158	Some concerns Details	Full description
NCT04364737 CONTAIN COVID-19 Ortigoza MB, JAMA Intern Med, 2021 Full text Commentary Commentary	Public/non profit	Convalescent plasma	Placebo	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to 21 centers in the USA.	N=941	Some concerns Details	Full description
NCT04600440 Holm K, BMC Res Notes, 2021 Full text Commentary	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to 2 centers in Sweden.	N=33	Some concerns Details	Full description
NCT04589949, NCT04621123 COMPILE home Millat-Martinez P, Nat Commun, 2022 Full text Full text Full text Commentary Commentary Commentary	Mixed	Convalescent plasma	Placebo	RCT	Outpatients with confirmed COVID-19 (mild, symptomatic) treated by 14 centers in Spain and the Netherlands.	N=797	Low Details	Full description
NCT04397757 PennCCP2 Bar KJ, J Clin Invest, 2021 Full text Full text Commentary	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (mild-severe) admitted to 2 centers in the USA.	N=80	Some concerns Details	Full description
NCT04373460 Sullivan D, N Engl J Med, 2022 Full text Full text Commentary Commentary Commentary	Mixed	Convalescent plasma	Placebo	RCT	Outpatients (symptomatic, mild) with confirmed COVID-19 treated at 23 centers in the USA.	N=1225	Low Details	Full description
NCT04716556 TSUNAMI Menichetti F, JAMA, 2021 Full text Commentary Commentary	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to 27 centers in Italy.	N=487	Some concerns Details	Full description
NCT04355767 SIREN-C3PO Korley F, N Engl J Med, 2021 Full text rid:crossref.org&rfr_dat=cr_pub%20%200pubmed Commentary	Public/non profit	Convalescent plasma	Placebo	RCT	Outpatients and patients with confirmed COVID-19 (symptomatic, mild to moderate) treated at or admitted to 48 centers in the USA.	N=511	Some concerns Details	Full description
NCT04542941 Kirenga B, BMJ Open Respir Res, 2021 Full text Commentary Commentary	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (asymptomatic-severe) admitted to a single center in Uganda.	N=136	Some concerns Details	Full description
NCT04547660 PLACOVID Sekine L, Eur Respir J, 2021 Full text Commentary	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to a single center in Brazil.	N=160	Some concerns Details	Full description
NCT04348656 CONCOR-1 Begin P, Nat Med, 2021 Full text Full text Commentary Commentary Commentary	Public/non profit	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to 72 centers in Canada, USA and Brazil.	N=940	Some concerns Details	Full description
NCT02735707 REMAP-CAP Estcourt L, JAMA, 2021 Full text Full text Commentary Commentary	Mixed	Convalescent plasma	Standard care	RCT	Patients with confirmed COVID-19 (severe-critical) admitted to 129 centers in Australia, Canada, UK, USA	N=2000	Low Details	Full description