#15,535
During the opening months of the COVID pandemic - before monoclonal antibodies, vaccines, and antiviral medications could be developed - a good deal of hope was pinned on a very old therapy (Convalescent Plasma) to treat those who were infected with this newly emerging virus.Convalescent plasma therapy - using blood products collected from recovered cases - is not a new idea, and was used extensively during the first half of the 20th century to treat a variety of infectious diseases.While its use gradually faded with the advent of powerful antibiotics and other drugs in the 20th century, the rise of new, mostly zoonotic viral diseases - for which few drug therapies are available - has sparked a revival in interest in convalescent plasma therapy in recent years.
Over the past decade we've seen some promising results (see 2011's CID Journal: Convalescent Plasma Therapy For Severe H1N1, 2015's Int J Infect Dis: Convalescent Plasma Treatment Of An H7N9 Patient In China), and even some early media reports on Convalescent Plasma treatment of COVID-19 in China.But we've also seen some high profile failures, such as 2019's Lancet: Clinical Trial On Use of Convalescent Plasma To Treat Severe Influenza, which disappointingly found that `High-titre anti-influenza plasma conferred no significant benefit over non-immune plasma' and 2016's NEJM: Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea, which reported no statistically significant improvement in survival over the control group.
While widely used in hospitalized patients in 2020 - bolstered by anecdotal reports suggesting improved outcomes - by the end of the first year of the pandemic, results from clinical trials began to erode confidence in this treatment option.
RECOVERY Convalescent Plasma Trial Closes Recruitment Of Hospitalized COVID Patients
Another Convalescent Plasma Study Fails To Find Benefit For Severe COVID-19
Despite these setbacks - and a substantial shift to other therapies in 2021 - there was still hope that delivered in a high enough dose, that Convalescent Plasma (CP) might still be an effective treatment for severe COVID disease.
Which brings us to a new research article out of Brazil that finds, once more, that even in high doses, CP did not reduce mortality or length of hospitalization.
I've only reproduced excerpts from a much longer report. Follow the link to read it in its entirety.
Volume 28, Number 3—March 2022
Research
High-Dose Convalescent Plasma for Treatment of Severe COVID-19
Gil C. De Santis, Luciana Correa Oliveira, Pedro M.M. Garibaldi, Carlos E.L. Almado, Julio Croda, Ghislaine G.A. Arcanjo, Érika A.F. Oliveira, Adriana C. Tonacio, Dante M. Langhi, José O. Bordin, Renato N. Gilio, Leonardo C. Palma, Elaine V. Santos, Simone K. Haddad, Benedito P.A. Prado, Marjorie Cornejo Pontelli, Rogério Gomes, Carlos H. Miranda, Maria Auxiliadora Martins, Dimas T. Covas, Eurico Arruda, Benedito A.L. Fonseca, and Rodrigo T. Calado
Abstract
To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19.
(SNIP)
In the past, passive antibody transfer by plasma or serum transfusion has been used clinically to treat other infectious diseases, including Ebola, influenza A, severe acute respiratory syndrome, and Middle East respiratory syndrome, as well as COVID-19 (9–13). The presence of antiviral antibodies, in patient serum or in COVID-19 convalescent plasma (CCP), has been associated with more favorable clinical outcomes (14). Thus, CCP seems to be an attractive therapy because it is a potential source of neutralizing antibodies (15,16).
(SNIP)
To evaluate the efficacy and safety of high-dose CCP transfusion to treat severe COVID-19, we conducted an open-label multicenter randomized controlled trial. This study was approved by the national review board (Comissão Nacional de Ética em Pesquisa, CONEP; CAAE number 30509920.0.1001.0008). Written informed consent was obtained from all patients or legal representatives. The trial was performed in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization–Good Clinical Practice guidelines. The trial was registered at the Brazilian Registry of Clinical Trials (http://www.ensaiosclinicos.gov.brExternal Link, no. RBR-7f4mt9f).
(SNIP)
Discussion
In this randomized clinical trial, transfusion of high-dose CCP did not reduce death rates, hospitalization durations, or number of days receiving mechanical ventilation for patients with very severe COVID-19. We detected a slightly reduced death rate, but it did not reach statistical significance. Serum inflammatory biomarkers were also reduced, but CCP transfusion did not influence the reduction. All enrolled patients experienced severe respiratory failure resulting from viral pneumonia, and most of them were undergoing invasive mechanical ventilation. Most patients had >1 concurrent condition, which increases mortality rates (25). More than one third of the enrolled patients needed kidney replacement therapy (hemodialysis). These characteristics emphasize the extreme severity of COVID-19 in the patients in our cohort. Participants received CCP as soon as possible, always within 10 days of symptom onset. This transfusion window was considered adequate at the time of the study planning and execution, especially when compared with other studies, in which transfusion occurred as late as day 39 (9). Of note, we observed that most trials evaluated the death rate at days 28 or 30 of randomization, but we observed that more than one fourth of the deaths in our study occurred during days 30–60.
(SNIP)
Among the limitations of our study, the number of patients enrolled was relatively small. However, because we anticipated difficulties obtaining the necessary amount of CCP to be administered to each patient, we decided to assign the participants at a ratio of 2 control to 1 CCP. Another weakness was that the study was not blinded. However, infusion of a high volume of intravenous placebo could have been harmful to recipients. Patients in the control group should not be exposed to additional risk as a consequence of their participation in a clinical trial. Another limitation was that our patients already had SARS-CoV-2 antibodies when they received CCP transfusion, which could explain the absence of response to this therapy.
In conclusion, our study found that high-dose convalescent plasma transfusion provided no benefits for patients with severe COVID-19. Transfusions did not reduce death rates at days 30 and 60 from randomization, time receiving mechanical ventilation, or length of hospital stay for patients with severe COVID-19.
Dr. De Santis is a clinical hematologist at the University of São Paulo. His research interests include blood transfusion and cellular therapy, such as laboratory support for hematopoietic stem cell transplantation.
