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Clinical Trial
. 2025 Feb 24;16(1):1929.
doi: 10.1038/s41467-025-57198-7.

Plasma exchange therapy for the post COVID-19 condition: a phase II, double-blind, placebo-controlled, randomized trial

Sergio España-Cueto  1   2 , Cora Loste  1   2   3 , Gemma Lladós  1   3   4 , Cristina López  1 , José Ramón Santos  1   2 , Gemma Dulsat  1 , Anna García  1 , João Carmezim  5 , Julia Carabia  1 , Águeda Ancochea  6 , Carla Fernández-Prendres  7 , Cristian Morales-Indiano  7 , Bibiana Quirant  4   8 , Eva Martínez-Cáceres  4   8 , Anna Sanchez  6 , Ivonne Graciela Parraga  6 , Anna Chamorro  1 , Alba San José  1 , Elena Abad  1 , Jose A Muñoz-Moreno  1   3   9 , Anna Prats  1   3 , Carmina R Fumaz  1   3 , Roser Coll-Fernández  3   10 , Carla Estany  1 , Pamela Torrano  1   4 , Jordi Puig  1   4 , Bonaventura Clotet  1   2   4   11   12 , Cristian Tebé  5 , Marta Massanella  3   11   12 , Roger Paredes  1   2   11   12   13 , Lourdes Mateu  14   15   16   17
Affiliations
Clinical Trial

Plasma exchange therapy for the post COVID-19 condition: a phase II, double-blind, placebo-controlled, randomized trial

Sergio España-Cueto et al. Nat Commun. .

Abstract

The post-COVID-19 condition (PCC) is a highly debilitating and persistent postinfectious syndrome that affects millions of people worldwide and has no effective treatment. Therapeutic plasma exchange (TPE) has the potential to improve the PCC by clearing the peripheral soluble pro-inflammatory immune milieu derived from acute or persistent SARS-CoV-2 infection. In a phase II, double-blind, placebo-controlled, randomized trial, fifty subjects with PCC were randomly assigned (1:1) to receive six sessions of either TPE or a sham plasma exchange and were followed for 90 days (ClinicalTrials.gov registration: NCT05445674). The primary endpoint was safety; secondary endpoints included functional status, symptomology, quality of life, neurocognitive symptoms, and peripheral biochemistry, hematology, coagulation and inflammation parameters. Both study arms had a similarly favorable safety profile. There were no diferences between groups in any of the efficacy parameters evaluated. Whereas TPE is safe, it did not lead to any discernible improvement of the PCC in this clinical trial.

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Conflict of interest statement

Competing interests: LM has received honoraria as speaker from Astra-Zeneca, Gilead, Shionogui and Pfizer, and has participated in advisory boards for Gilead and MSD. CL has received support for attending meetings from Gilead. AG has received grants from Grifols, honoraria for lectures or presentations from Astra-Zeneca, Gilead, and Pfizer and has participated on DSMB or advisory boards for Gilead and MSD. RP hasparticipated in advisory boards for Pfizer, Gilead, MSD, GSK, Atea, Lilly, Roche, Astra-Zeneca, ViiV Healthcare and Theratechnologies, has participated in lectures and seminars funded by Gilead, Pfizer,GSK and AstraZeneca, and has received research funds awarded to his institution from Gilead, Pfizer and MSD. MM has received honoraria for participating in lectures and seminars funded by Gilead, not related to this project.

Figures

Fig. 1
Fig. 1
CONSORT diagram.
Fig. 2
Fig. 2. Evolution of the mean score of the PCFS, Can Ruti PCC Symptoms Scale, FSS and EuroQol-5D score in the two groups over time.
a Post-COVID-19 Functional Status scale at screening, day 45 and day 90 after the intervention in the Plasma Exchange and placebo arms. “No” indicates no improvement and “Yes” denotes an improvement. b Evolution of Post COVID-19 Condition symptoms (PCC symptoms) throughtout the study of the Plasma Exchange (Turquoise) and Placebo arms (red). The plot depicts the total score obtained in the German Trias’ Long COVID symptom questionnaire at day 0, 8, 15, 22, 45 and 90 of the study. c Evolution of the Fatigue throught the study in both groups. The plot depicts the total score of the Fatigue Severity Scale obtained at days 0, 8, 15, 22, 45 and 90 of the study. d Evolution of the quality of life of participants in both groups. The plot shows the total EuroQol-5D score obtained at days 0, 8, 15, 22, 45 and 90 of the study, exploring different areas: Mobility (dark blue), Self care (orange), Usual activities (green), Pain/discomfort (light blue) and Anxiety/depression (purple).
Fig. 3
Fig. 3. Neuropsychological assessment.
A battery of neurocognitive tests were perfomed at day 0, 22 and 90 of the study for participants of Plasma Exchange (Turquoise) and placebo arms (red) to evaluate cognitive status, including Neu Screen (a) Semantic Fluency test (b) Memory Failures in Everyday questionnaire (c) and Hospital Anxiety and Depression Score (d).
Fig. 4
Fig. 4. Analytical parameters evolution post Plasma Exchange versus Placebo.
A battery of analytical paramenters were perfomed at day 0, 8, 15, 22, 45 and 90 of the study in Plasma Exchange (Turquoise) and placebo arms (red), including biochemistry, hematology and inflammatory and coagulation parameters.
See this image and copyright information in PMC

References

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