Convalescent Plasma for COVID-19: real-time analysis of all 17 studies

International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship

Raad et al., medRxiv, doi:10.1101/2022.08.25.22279181 (Preprint)

Retrospective 3,966 COVID-19 patients, 1,115 with cancer, showing lower mortality with remdesivir and higher mortality with convalescent plasma.

risk of death, 240.0% higher, OR 3.40, p < 0.001, treatment 284, control 3,682, adjusted, multivariable, day 30, RR approximated with OR.

Raad et al., 26 Aug 2022, retrospective, multiple countries, preprint, 52 authors, study period January 2020 - November 2020.

Outpatient convalescent plasma therapy for high-risk patients with early COVID-19. A randomized placebo-controlled trial

Gharbharan et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2022.08.005

RCT 416 outpatients in the Netherlands, showing no significant difference with convalesent plasma treatment. Hospitalization was lower, and improved results were seen with ≤5 days of symptoms, without statistical significance.

risk of death, 1.0% higher, RR 1.01, p = 1.00, treatment 1 of 207 (0.5%), control 1 of 209 (0.5%), day 28.

risk of mechanical ventilation, 66.6% lower, RR 0.33, p = 1.00, treatment 0 of 207 (0.0%), control 1 of 209 (0.5%), NNT 209, relative risk is not 0 because of continuity correction due to zero events, day 28.

risk of progression, 14.0% lower, OR 0.86, p = 0.42, treatment 207, control 209, adjusted, improved severity score, RR approximated with OR.

risk of progression, 42.0% lower, OR 0.58, p = 0.06, treatment 123, control 103, adjusted, improved severity score, ≤5 days, RR approximated with OR.

risk of hospitalization, 39.0% lower, HR 0.61, p = 0.22, treatment 10 of 207 (4.8%), control 18 of 209 (8.6%), NNT 26, adjusted, day 28.

hospitalization time, 50.0% higher, relative time 1.50, p = 0.56, treatment 207, control 209.

risk of no recovery, 1.0% higher, RR 1.01, p = 0.92, treatment 137 of 207 (66.2%), control 137 of 209 (65.6%), continued COVID-19 symptoms, day 27.

recovery time, 8.3% higher, relative time 1.08, p = 0.99, treatment 207, control 209.

Gharbharan et al., 23 Aug 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Netherlands, peer-reviewed, 59 authors, study period November 2020 - July 2021, average treatment delay 5.0 days, trial NCT04589949 (history).

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial

Alemany et al., The Lancet Respiratory Medicine, doi:10.1016/S2213-2600(21)00545-2

RCT 188 convalescent plasma and 188 control patients, showing no significant difference in outcomes.

risk of death, 80.0% lower, RR 0.20, p = 0.50, treatment 0 of 188 (0.0%), control 2 of 188 (1.1%), NNT 94, relative risk is not 0 because of continuity correction due to zero events.

risk of hospitalization, 4.8% higher, RR 1.05, p = 1.00, treatment 22 of 188 (11.7%), control 21 of 188 (11.2%).

risk of no recovery, 5.0% higher, HR 1.05, p = 0.67, treatment 188, control 188, time to symptom resolution.

viral load, 3.6% higher, relative load 1.04, p = 0.33, treatment 188, control 188, relative change in viral load, day 28.

viral load, 3.7% lower, relative load 0.96, p = 0.42, treatment 188, control 188, relative change in viral load, day 7.

Alemany et al., 9 Feb 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Spain, peer-reviewed, median age 56.0, 108 authors, study period 10 November, 2020 - 28 July, 2021, trial NCT04621123 (history).

Early Outpatient Treatment for Covid-19 with Convalescent Plasma

Sullivan et al., New England Journal of Medicine, doi:10.1056/NEJMoa2119657 (preprint 12/21/2021)

RCT 1,181 outpatients in the USA, mean 6 days from symptom onset, showing lower hospitalization with treatment. NCT04373460.

risk of death, 85.7% lower, RR 0.14, p = 0.12, treatment 0 of 592 (0.0%), control 3 of 589 (0.5%), NNT 196, relative risk is not 0 because of continuity correction due to zero events.

risk of ICU admission, 25.4% lower, RR 0.75, p = 0.73, treatment 3 of 592 (0.5%), control 4 of 589 (0.7%), NNT 580.

risk of hospitalization, 54.3% lower, RR 0.46, p = 0.005, treatment 17 of 592 (2.9%), control 37 of 589 (6.3%), NNT 29.

Sullivan et al., 21 Dec 2021, Double Blind Randomized Controlled Trial, USA, peer-reviewed, 58 authors, study period 3 June, 2020 - 1 October, 2021, average treatment delay 6.0 days, trial NCT04373460 (history).

Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial

Bégin et al., Nature Medicine, doi:10.1038/s41591-021-01488-2

RCT 940 hospitalized patients, 614 assigned to convalescent plasma, showing no significant differences. NCT04348656.

risk of death, 13.0% higher, RR 1.13, p = 0.33, treatment 156 of 625 (25.0%), control 69 of 313 (22.0%), day 90.

risk of death, 12.0% higher, RR 1.12, p = 0.40, treatment 141 of 614 (23.0%), control 63 of 307 (20.5%), day 30.

risk of death/intubation, 16.0% higher, RR 1.16, p = 0.18, treatment 199 of 614 (32.4%), control 86 of 307 (28.0%), primary outcome.

Bégin et al., 9 Sep 2021, Randomized Controlled Trial, multiple countries, peer-reviewed, 32 authors, average treatment delay 8.0 days, trial NCT04348656 (history).

Early Convalescent Plasma for High-Risk Outpatients with Covid-19

Korley et al., NEJM, doi:10.1056/NEJMoa2103784

RCT 511 emergency department patients, 257 assigned to convalescent plasma, showing no significant difference in outcomes.

risk of death, 396.0% higher, RR 4.96, p = 0.22, treatment 5 of 250 (2.0%), control 1 of 248 (0.4%).

risk of hospitalization, 10.0% lower, RR 0.90, p = 0.59, treatment 51 of 257 (19.8%), control 56 of 254 (22.0%), NNT 45.

risk of progression, 6.0% lower, RR 0.94, p = 0.70, treatment 77 of 257 (30.0%), control 81 of 254 (31.9%), NNT 52.

Korley et al., 18 Aug 2021, Randomized Controlled Trial, USA, peer-reviewed, 28 authors, average treatment delay 3.7 days.

Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial

Balcells et al., PLOS Medicine, doi:10.1371/journal.pmed.1003415

Small RCT with 28 early and 30 deferred (treated according to prespecified deterioration criteria) convalescent plasma patients, not showing significant differences. "Early" is relative, with a median of 5 days from symptom onset. 13 patients in the deferred group received plasma.

risk of death, 247.4% higher, RR 3.47, p = 0.17, treatment 5 of 28 (17.9%), control 2 of 30 (6.7%), adjusted, OR converted to RR, logistic regression, early vs. deferred.

risk of mechanical ventilation, 163.3% higher, RR 2.63, p = 0.22, treatment 5 of 28 (17.9%), control 2 of 30 (6.7%), adjusted, OR converted to RR, logistic regression, early vs. deferred.

risk of progression, 23.3% higher, RR 1.23, p = 0.51, treatment 13 of 28 (46.4%), control 12 of 30 (40.0%), adjusted, OR converted to RR, logistic regression, early vs. deferred.

Balcells et al., 3 Mar 2021, Randomized Controlled Trial, Chile, peer-reviewed, 32 authors, average treatment delay 5.0 days.

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Recovery Collaborative Group, The Lancet, doi:10.1016/S0140-6736(21)00897-7 (press release 1/15/2021)

RCT 16,287 hospitalized patients in the UK, showing no significant differences with convalescent plasma treatment. Subgroup analysis shows better results for those treated <= 7 days from symptom onset.

risk of death, no change, RR 1.00, p = 0.95, treatment 1,399 of 5,795 (24.1%), control 1,408 of 5,763 (24.4%), NNT 345, day 28, primary outcome.

risk of no hospital discharge, 1.0% higher, RR 1.01, p = 0.57, treatment 1,963 of 5,795 (33.9%), control 1,941 of 5,763 (33.7%), inverted to make RR<1 favor treatment, day 28.

Recovery Collaborative Group et al., 15 Jan 2021, Randomized Controlled Trial, United Kingdom, peer-reviewed, 1 author, average treatment delay 9.0 days, trial NCT04381936 (history) (RECOVERY).

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

Libster et al., NEJM, doi:10.1056/NEJMoa2033700

RCT 160 patients >=65 with symptom onset <72 hours, 80 treated with convalescent plasma, showing lower progression to severe disease with treatment. NCT04479163.

risk of death, 50.0% lower, RR 0.50, p = 0.43, treatment 2 of 80 (2.5%), control 4 of 80 (5.0%), NNT 40.

risk of mechanical ventilation, 50.0% lower, RR 0.50, p = 0.43, treatment 2 of 80 (2.5%), control 4 of 80 (5.0%), NNT 40.

risk of ICU admission, 67.0% lower, RR 0.33, p = 0.17, treatment 2 of 80 (2.5%), control 6 of 80 (7.5%), NNT 20.

risk of progression, 48.0% lower, RR 0.52, p = 0.03, treatment 13 of 80 (16.2%), control 25 of 80 (31.2%), NNT 6.7.

Libster et al., 6 Jan 2021, Double Blind Randomized Controlled Trial, Argentina, peer-reviewed, 56 authors, trial NCT04479163 (history).

Clinical and immunological benefits of convalescent plasma therapy in severe COVID-19: insights from a single center open label randomised control trial

Ray et al., medRxiv, doi:10.1101/2020.11.25.20237883

Small RCT 80 hospitalized patients in India, 40 treated with convalescent plasma, not showing significant differences in primary analysis. Authors note that significant improvement in hypoxia, reduction in hospital stay, and survival benefit was seen in severe COVID-19 patients with ARDS aged <67. CTRI/2020/05/025209.

risk of death, 33.0% lower, HR 0.67, p = 0.34, treatment 10 of 40 (25.0%), control 14 of 40 (35.0%), NNT 10, adjusted, Mantel-Haenszel, primary outcome.

Ray et al., 29 Nov 2020, Randomized Controlled Trial, India, peer-reviewed, 37 authors.

A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia

Simonovich et al., NEJM, doi:0.1056/NEJMoa2031304

RCT 333 hospitalized patients in Argentina, 228 treated with convalescent plasma, showing no significant differences in clinical status or mortality. NCT04383535.

risk of death, 4.1% lower, RR 0.96, p = 1.00, treatment 25 of 228 (11.0%), control 12 of 105 (11.4%), NNT 216.

risk of 7-point scale, 19.0% lower, OR 0.81, p = 0.40, treatment 228, control 105, RR approximated with OR.

Simonovich et al., 24 Nov 2020, Randomized Controlled Trial, Argentina, peer-reviewed, 39 authors, average treatment delay 8.0 days, trial NCT04383535 (history).

Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

AlQahtani et al., Scientific Reports, doi:10.1038/s41598-021-89444-5 (preprint 11/4/2020)

Small RCT with 40 hospitalized patients in Bahrain, 20 treated with convalescent plasma, not showing significant differences. NCT04356534.

risk of death, 50.0% lower, RR 0.50, p = 0.55, treatment 1 of 20 (5.0%), control 2 of 20 (10.0%), NNT 20.

noninvasive or mechanical ventilation, 33.3% lower, RR 0.67, p = 0.47, treatment 4 of 20 (20.0%), control 6 of 20 (30.0%), NNT 10, primary outcome.

hospitalization time, 21.9% lower, relative time 0.78, p = 0.12, treatment 20, control 20.

AlQahtani et al., 4 Nov 2020, Randomized Controlled Trial, Bahrain, peer-reviewed, 11 authors, trial NCT04356534 (history).

Efficacy of Convalescent Plasma Therapy compared to Fresh Frozen Plasma in Severely ill COVID-19 Patients: A Pilot Randomized Controlled Trial

Bajpai et al., medRxiv, doi:10.1101/2020.10.25.20219337 (Preprint)

Small RCT 29 patients in India, 14 treated with convalescent plasma, not showing significant differences with treatment.

risk of death, 323.0% higher, HR 4.23, p = 0.22, treatment 3 of 14 (21.4%), control 1 of 15 (6.7%), adjusted, 28 days, Cox proportional hazards.

risk of death, 114.3% higher, RR 2.14, p = 0.60, treatment 2 of 14 (14.3%), control 1 of 15 (6.7%), 7 days.

risk of mechanical ventilation, 221.4% higher, RR 3.21, p = 0.33, treatment 3 of 14 (21.4%), control 1 of 15 (6.7%), 7 days.

hospitalization time, 24.8% lower, relative time 0.75, p = 0.08, treatment 14, control 15.

relative improvement in Ct value, 32.5% better, RR 0.68, p = 0.11, treatment 14, control 15.

Bajpai et al., 27 Oct 2020, Randomized Controlled Trial, India, preprint, 20 authors.

Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)

Agarwal et al., BMJ, doi:10.1136/bmj.m3939

RCT 464 hospitalized patients in India, 235 treated with convalescent plasma, showing no improvement in combined death at 28 days or progression to severe disease. CTRI/2020/04/024775.

risk of death, 7.0% higher, RR 1.07, p = 0.74, treatment 34 of 235 (14.5%), control 31 of 229 (13.5%).

combined death at 28 days or progression to severe disease, 7.0% higher, RR 1.07, p = 0.74, treatment 44 of 235 (18.7%), control 41 of 229 (17.9%).

risk of mechanical ventilation, 1.0% lower, RR 0.99, p = 0.98, treatment 19 of 227 (8.4%), control 19 of 224 (8.5%), NNT 892.

risk of no viral clearance, 28.0% lower, RR 0.72, p = 0.02, treatment 56 of 173 (32.4%), control 76 of 169 (45.0%), NNT 7.9, day 7.

Agarwal et al., 22 Oct 2020, Randomized Controlled Trial, India, peer-reviewed, 6 authors, average treatment delay 8.0 days.

Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial

Avendaño-Solà et al., medRxiv, doi:10.1101/2020.08.26.20182444

Early terminated RCT with 81 hospitalized patients, 38 treated with convalescent plasma, showing lower progression with treatment. NCT04345523.

risk of death, 88.3% lower, RR 0.12, p = 0.12, treatment 0 of 38 (0.0%), control 4 of 43 (9.3%), NNT 11, relative risk is not 0 because of continuity correction due to zero events, day 29.

risk of progression, 93.0% lower, RR 0.07, p = 0.01, treatment 0 of 38 (0.0%), control 7 of 43 (16.3%), NNT 6.1, relative risk is not 0 because of continuity correction due to zero events, day 29, progression to categories 5-7.

risk of progression, 91.9% lower, RR 0.08, p = 0.03, treatment 0 of 38 (0.0%), control 6 of 43 (14.0%), NNT 7.2, relative risk is not 0 because of continuity correction due to zero events, day 15, progression to categories 5-7, primary outcome.

Avendaño-Solà et al., 29 Sep 2020, Randomized Controlled Trial, Spain, peer-reviewed, 36 authors, average treatment delay 8.0 days, trial NCT04345523 (history).

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial

Li et al., JAMA, doi:10.1001/jama.2020.10044

Small RCT 103 severe condition patients, 52 treated with convalescent plasma, showing improved viral clearance but no statistically significant improvements in mortality or clinical improvement. ChiCTR2000029757.

risk of death, 34.6% lower, RR 0.65, p = 0.30, treatment 8 of 51 (15.7%), control 12 of 50 (24.0%), NNT 12, OR converted to RR, 28 days.

risk of no improvement, 15.3% lower, RR 0.85, p = 0.37, treatment 25 of 52 (48.1%), control 29 of 51 (56.9%), NNT 11, inverted to make RR<1 favor treatment, OR converted to RR, 28 days.

risk of no viral clearance, 76.4% lower, RR 0.24, p = 0.01, treatment 4 of 26 (15.4%), control 15 of 23 (65.2%), NNT 2.0, inverted to make RR<1 favor treatment, OR converted to RR.

Li et al., 3 Jun 2020, Randomized Controlled Trial, China, peer-reviewed, 34 authors.

Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection

Gharbharan et al., Nature Communications, doi:10.1038/s41467-021-23469-2

RCT 86 hospitalized patients, 43 treated with convalescent plasma, showing no significant differences with treatment. Authors conclude that the most likely explanation was already high antibody titers on the day of inclusion, and they recommend treating patients early. NCT04342182.

risk of death, 3.8% lower, RR 0.96, p = 0.95, treatment 6 of 43 (14.0%), control 11 of 43 (25.6%), NNT 8.6, adjusted, OR converted to RR, multivariable logistic regression, primary outcome.

time to discharge, 11.7% lower, relative time 0.88, p = 0.68, treatment 43, control 43, adjusted, multivariable Fine and Gray regression.

Gharbharan et al., 27 May 2020, Randomized Controlled Trial, Netherlands, peer-reviewed, 32 authors, average treatment delay 10.0 days, trial NCT04342182 (history).