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

Alemany, Andrea; Millat-Martinez, Pere; Corbacho-Monné, Marc; Malchair, Pierre; Ouchi, Dan; Ruiz‐Comellas, Anna; Ramírez‐Morros, Anna; Codina, Joana Rodríguez; Simon, Rosa Amado; Videla, Sebastián; Costes, Gèlia; Capdevila-Jáuregui, Mar; Torrano-Soler, Pamela; José, Alba San; Papell, Glòria Bonet; Puig, Jordi; Otero, Aurema; Suárez, José; Pellejero, A.; Roca, Ferrán Llopis; Cortez, Orlando Rodriguez; Garcia, Vanesa Garcia; Vidal‐Alaball, Josep; Millan, Anna; Contreras, Enric; Grífols, Joan-Ramon; Ancochea, Águeda; Galván-Femenía, Iván; Ferreira, Francini Piccolo; Bonet, Mireia; Cantoni, Jordi; Prat, Núria; Ara, Jordi; Arcarons, Anna Forcada; Farré, Magı́; Pradenas, Edwards; Blanco, Julià; Rodríguez-Arias, Miquel Àngel; Rivas, Gema Fernández; Marks, Michael; Bassat, Quique; Blanco, Ignacio; Baró, Bàrbara; Clotet, Bonaventura; Mitjà, Oriol; Ferrer, Susana; Gallardo, M. Lebron; Ubals, María; González-Beiras, Camila; Vall-Mayans, Martí; Suñer, Clara; Laporte-Villar, Clàudia; Nieto, Aroa; Comas-Leon, Xavier; Jiménez, Z. Abad; Ramírez-Viaplana, Ferran; Delgado-Capel, Maria; Sánchez, Beatriz; Barber, Maria Pons; Ruiz, Cristian Gonzalez; Gonzalez, Laura Navarrete; García, David González; Larraza, Ainhoa Vivero; Peiró, Victor Carceles; Lopez, Claudia; Robert, Neus; Palet, Carles; Gudiol, Carlota; Gonzalez, Pablo Casares; G, Vila; Aguilera, Begoña Flores; Rodríguez-Sevilla, Graciela; Arias, Macarena Dastis; Font, Judit Roca; Matos, Katherine M. Carrasco; Valmaña, Glòria Sauch; Obradors, Carla Vidal; García, Silvia Tarres; Sabatès, Margarida Curriu; Rodríguez, Raquel Nieto; Línio, Rosa; Fornos, M Morales; Casamitjana, Natàlia; Alonso, E Fernández; Martínez, Núria; Maglio, Laura Analía; Fernandez, Laura Comellas; García, Nadia L. González; Hernández, Luís E.; Gonzalez, Maria; Bravo, A. Palomo; García, Yolanda; Oliveras, Sílvia Sauleda; Vertiz, Tatiana; Benavent, Sergio; Bianco, Andrea S.; Verdaguer, Joaquim; Zambrano, Ney Nicanor Briones; Meya, Maria Viozquez; Hernández, Á; Lopez, Cristina Casaña; Bordoy, Antoni E.; Soler, Victoria González; Giménez, Montserrat; París, Alexa; Marfil, Sílvia; Trinité, Benjamín; Grau, Eulàlia

doi:10.1016/s2213-2600(21)00545-2

Cited by 65 publications

(69 citation statements)

References 36 publications

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“…However, subsequent hospitalization and adverse events in the CCP arm were less frequent than in controls transfused with nonconvalescent plasma. On the other hand, in the clinical trial conducted by Alemany et al, 31 CCP administered soon after infection did not prevent hospitalization in the subsequent days. Still, the study was underpowered because of the early termination of the trial.…”

Section: Discussionmentioning

confidence: 86%

Efficacy of early transfusion of convalescent plasma with high‐titer SARS‐CoV‐2 neutralizing antibodies in hospitalized patients with COVID‐19

et al. 2022

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Background Despite most controlled trials have shown no measurable benefit of COVID‐19 convalescent plasma (CCP) in patients with COVID‐19, some studies suggest that early administration of CCP with high‐titer anti‐SARS‐CoV‐2 can be beneficial in selected patients. We investigated the efficacy of early administration of high‐titer CCP to patients with COVID‐19 who required hospitalization, Study design and methods Observational, propensity score (PS) matched case–control study of COVID‐19 patients treated with CCP within 72 h of hospital admission and untreated controls from August 2020 to February 2021. All CCP donations had a Euroimmun anti‐SARS‐CoV‐2 sample‐to‐cutoff ratio ≥3. PS matching was based on prognostic factors and presented features with high‐standardized differences between the treated and control groups. The primary endpoint was mortality within 30 days of diagnosis. Results A total of 1604 patients were analyzed, 261 of whom received CCP, most (82%) within 24 h after admission. Median age was 67 years (interquartile range: 56–79), and 953 (60%) were men. Presenting factors independently associated with higher 30‐day mortality were increased age, cardiac disease, hypoxemic respiratory failure, renal failure, and plasma d‐dimer >700 ng/ml. After PS matching, transfusion of CCP was associated with a significant reduction in the 30‐day mortality rate (odds ratio [OR]; 0.94, 95% confidence interval [CI]: 0.91–0.98; p = .001) that extended to the 60th day after COVID‐19 diagnosis (OR: 0.95; 95% CI: 0.92–0.99; p = .01). Conclusion Our results suggest that CCP can still be helpful in selected patients with COVID‐19 and call for further studies before withdrawing CCP from the COVID‐19 therapeutic armamentarium.

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Section: Discussionmentioning

confidence: 86%

Efficacy of early transfusion of convalescent plasma with high‐titer SARS‐CoV‐2 neutralizing antibodies in hospitalized patients with COVID‐19

et al. 2022

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“…A total of 49 RCTs ( N = 43,943) reported the incidence of mortality. Excluding five studies using plasma controls [ 26 – 30 ], 44 studies ( N = 42,604) [ 15 – 19 , 22 , 31 , 41 – 49 , 52 – 55 , 57 – 70 , 72 , 74 – 82 ] were included in the NMA. Follow-up durations for mortality ranged from 30 to 90 days.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 9 RCTs [ 15 , 16 , 53 , 55 , 60 , 72 , 74 , 77 , 82 ] reported the incidence of hospitalization in 10,234 outpatients and were included in the NMA. At baseline, the trial by O’Brien et al [ 82 ] only included asymptomatic outpatients, three studies [ 53 , 60 , 77 ] included outpatients who are not using supplemental oxygen, and four studies [ 15 , 16 , 55 , 74 ] included outpatients with mild to moderate COVID-19 based on the FDA severity classification. All studies except publications reporting on the BLAZE-1 trial only included outpatients who had symptom onset less than a week before randomization.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 30 studies ( N = 11,403) reported the incidence of all-cause adverse events. Excluding two studies using plasma controls, 28 studies ( N = 11,150) [ 15 , 16 , 19 , 41 , 42 , 44 , 45 , 51 , 53 , 55 , 57 – 61 , 63 – 66 , 69 , 70 , 74 , 76 – 78 , 80 – 82 ] were included in the NMA. All antibody products, except convalescent plasma and anti-COVID IVIg, demonstrated good safety profiles with no significant increase in the odds of adverse events.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 30 studies ( N = 19,887) patients reported the incidence of serious adverse events. Following the exclusion of two studies using plasma controls, 28 studies ( N = 19,611) [ 15 , 16 , 19 , 41 , 42 , 46 , 48 , 49 , 51 – 53 , 55 , 58 , 60 , 61 , 65 , 68 – 74 , 76 – 78 , 80 , 82 ] were included in the NMA. No antibody product was associated with a significant increase in the odds of serious adverse events.…”

Section: Resultsmentioning

confidence: 99%

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Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis

et al. 2022

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Purpose To assess and compare the relative efficacy and safety of anti-SARS-CoV-2 antibody regimens for COVID-19. Methods This systematic review and random-effects network meta-analysis was conducted according to PRISMA-NMA. Literature searches were conducted across MEDLINE, EMBASE, PubMed, Web of Science, CENTRAL, and CNKI up to February 20th, 2022. Interventions were ranked using P scores. Results Fifty-five RCTs ( N = 45,005) were included in the review. Bamlanivimab + etesevimab (OR 0.13, 95% CI 0.02–0.77) was associated with a significant reduction in mortality compared to standard of care/placebo. Casirivimab + imdevimab reduced mortality (OR 0.67, 95% CI 0.50–0.91) in baseline seronegative patients only. Four different regimens led to a significant decrease in the incidence of hospitalization compared to standard of care/placebo with sotrovimab ranking first in terms of efficacy (OR 0.20, 95% CI 0.08–0.48). No treatment improved incidence of mechanical ventilation, duration of hospital/ICU stay, and time to viral clearance. Convalescent plasma and anti-COVID IVIg both led to a significant increase in adverse events compared to standard of care/placebo, but no treatment increased the odds of serious adverse events. Conclusion Anti-SARS-CoV-2 mAbs are safe, and could be effective in improving mortality and incidence of hospitalization. Convalescent plasma and anti-COVID IVIg were not efficacious and could increase odds of adverse events. Future trials should further examine the effect of baseline seronegativity, disease severity, patient risk factors, and SARS-CoV-2 strain variation on the efficacy of these regimes. Registration PROSPERO-CRD42021289903. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-022-01825-8.

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Convalescent plasma for people with COVID-19: a living systematic review

Iannizzi

Chai

Piechotta

et al. 2023

Cochrane Database of Systematic Reviews

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

Cited by 65 publications

References 36 publications

Efficacy of early transfusion of convalescent plasma with high‐titer SARS‐CoV‐2 neutralizing antibodies in hospitalized patients with COVID‐19

Efficacy of early transfusion of convalescent plasma with high‐titer SARS‐CoV‐2 neutralizing antibodies in hospitalized patients with COVID‐19

Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis

Convalescent plasma for people with COVID-19: a living systematic review

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