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1.
Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection
Gharbharan, A., Jordans, C. C. E., GeurtsvanKessel, C., den Hollander, J. G., Karim, F., Mollema, F. P. N., Stalenhoef-Schukken, J. E., Dofferhoff, A., Ludwig, I., Koster, A., et al
Nature Communications. 2021;12(1):3189
Abstract
In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.
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2.
COVID-19 Convalescent Plasma: from donation to treatment - A Systematic Review & Single Center Experience
Fabricius, M. M., Dandachi, D.
Missouri medicine. 2021;118(1):74-80
Abstract
Convalescent plasma is an old treatment for a new disease. The coronavirus disease 2019 (COVID-19) pandemic caused the analysis of convalescent plasma to reemerge as a possible treatment. First, a systematic review summarizes the available research examining the use of convalescent plasma for the treatment of patients with COVID-19. Second, we describe our experience in establishing a single-center convalescent plasma donation program.
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3.
Neutralizing Activity to SARS-CoV-2 of Convalescent and Control Plasma Used in a Randomized Controlled Trial
Freedenberg, A. T., Pan, C. H., Diehl, W. E., Romeiser, J. L., Hwang, G. R., Leiton, C. V., Muecksch, F., Shroyer, K. R., Bennett-Guerrero, E.
Transfusion. 2021
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Abstract
BACKGROUND There are limited data on the neutralizing activity of convalescent plasma (CP) administered in randomized controlled trials (RCT) of COVID-19 infection. STUDY DESIGN AND METHODS As part of an RCT, CP was collected per FDA guidelines from individuals recovered from COVID-19 infection. CP donors had to have ≥145 optical density (OD) units (ideal target ≥300) using a semi quantitative, immunochromatographic test for IgG antibody to the nucleocapsid protein (NP) of SARS-CoV-2 (typical range 0-500 OD units). A random subset of samples [14 control plasma, 12 CP "medium-anti-NP" (145-299 OD units), and 13 CP "high" anti-NP (≥300 OD units)] were tested for neutralizing antibodies using an established viral luciferase antibody inhibition assay to detect the infection of SARS-CoV-2 pseudovirus that encoded spike protein (SARS2-S(trunc) ) on a human immunodeficiency virus 1 vector (NL43dEnvNanoLuc), using ACE2-expressing 293T cells. The titer needed to neutralize 50% of viral activity (NT50) was calculated. RESULTS The uptake of SARS-CoV-2 pseudovirus by 293T(ACE2) cells was inhibited by pretreatment with CP compared to control CP (p<0.001) with control plasma having a median (IQR) 50% neutralization titer (NT50) of 1:28 (1:16,1:36) compared to 1:334 (1:130,1:1295) and 1:324 (1:244,1:578), for medium anti-NP and high anti-NP CP units, respectively. The neutralizing activity of CP met minimum FDA criteria with neutralizing antibody titers >1:80 in 100% of randomly selected samples, using a conservative approach that excluded non-specific binding. DISCUSSION Plasma from donors screened using an immunochromatographic test for IgG antibody to SARS-CoV-2 NP exhibited neutralizing activity meeting FDA's minimum standard in all randomly selected COVID-19 CP units. This article is protected by copyright. All rights reserved.
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4.
Impact of pathogen-reduction technologies on COVID-19 convalescent plasma potency
Focosi, D., Franchini, M.
Transfus. clin. biol. 2021
Abstract
Pathogen reduction technologies (PRT) have been recommended by many regulatory authorities to minimize the residual risk of transfusion-transmitted infections associated with COVID19 convalescent plasma. While its impact on safety and its cost-effectiveness are nowadays well proven, there is theoretical concern that PRT could impact efficacy of convalescent plasma by altering concentration and/or function of the neutralizing antibodies (nAb). We review here the evidence supporting a lack of significant detrimental effect from PRTs on nAbs.
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5.
Systematic review and meta-analysis of randomised controlled trials testing the safety and efficacy of convalescent plasma in the treatment of coronavirus disease 2019 (COVID-19): Evidence-base for practise and implications for research
Gupta, T., Kannan, S., Kalra, B., Thakkar, P.
Transfusion Medicine (Oxford, England). 2021
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Abstract
BACKGROUND Despite scientific advances, there is no effective medical therapy for coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis aimed to evaluate the safety and efficacy of convalescent plasma therapy in COVID-19. METHODS This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Only prospective clinical trials randomly assigning COVID-19 patients to convalescent plasma plus standard of care therapy (test arm) versus placebo/standard of care (control arm) were included. Two reviewers independently read each preprint/publication and extracted relevant data from individual studies. Data were pooled using the random-effects model and expressed as risk ratio (RR) with 95% confidence interval (CI). RESULTS A total of 13 206 patients from 12 randomised controlled trials were included. There was no significant difference in clinical improvement rate (RR = 1.00, 95% CI: 0.98-1.02, p = 0.96) or time to clinical improvement (median difference of 1.08 days with 95% CI ranging from -0.15 to +2.30 days) between convalescent plasma versus placebo/standard of care therapy. The use of convalescent plasma was not associated with significantly reduced risk of death (RR = 0.81, 95% CI: 0.65-1.02, p = 0.08). Reassuringly, overall incidence of infusion-related serious adverse events was low (3.25%) and not significantly different (RR = 1.14, 95% CI: 0.93-1.40, p = 0.22) for convalescent plasma transfusion compared to placebo/standard of care therapy. CONCLUSIONS There is low to moderate certainty evidence that the addition of convalescent plasma to current standard of care therapy is generally safe but, does not result in any significant clinical benefit or reduction of mortality in COVID-19.
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COVID-19 Convalescent Plasma: from donation to treatment - A Systematic Review & Single Center Experience
Fabricius, Michela M., Dandachi, Dima
Mo Med. 2021;118(1):74-80
Abstract
Convalescent plasma is an old treatment for a new disease. The coronavirus disease 2019 (COVID-19) pandemic caused the analysis of convalescent plasma to reemerge as a possible treatment. First, a systematic review summarizes the available research examining the use of convalescent plasma for the treatment of patients with COVID-19. Second, we describe our experience in establishing a single-center convalescent plasma donation program.
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7.
Convalescent Plasma for Pregnant Women with COVID-19: A Systematic Literature Review
Franchini, M., Prefumo, F., Grisolia, G., Bergamini, V., Glingani, C., Pisello, M., Presti, F., Zaffanello, M.
Viruses. 2021;13(7)
Abstract
The treatment of COVID-19 is particularly critical in pregnant women, considering the potential teratogenic effects of antiviral agents and the immune-depression related with pregnancy. The aim of this review is to systematically examine the current evidence on the clinical use of convalescent plasma during pregnancy. The electronic databases Medline PubMed Advanced Search Builder, Scopus, Web Of Science and Google Scholar were searched (until 1 January 2021). Inclusion criteria were pregnant women with COVID-19 (or SARS-CoV-2 infection), in whom convalescent plasma (or hyperimmune plasma) was used as treatment. We searched clinical trial registries (censored 5 January 2021) for eligible studies under way. After elimination of duplications, the initial search yielded 79 potentially relevant records, of which 67 were subsequently excluded. The 12 remaining records were case reports involving 12 pregnancies. Six of the mothers were reported to be well, two were reported to have preeclampsia, and in one case each the maternal outcome was described as survival, clinical improvement, discharged with oxygen and rehabilitation. With regard to the neonates, two were declared to be well, four had transient morbidity, two were critically ill and one died; normal ongoing pregnancies, but no post-delivery information, were reported for the remaining three cases. Clinical trials under way or planned to investigate the use of convalescent plasma for COVID-19 during pregnancy are lacking. This is the first systematic review of the literature regarding the treatment of COVID-19 in pregnancy. The published literature data seem to indicate that convalescent plasma administered to pregnant women with severe COVID-19 provides benefits for both the mother and the fetus. The quality of the available studies is, however, very limited since they are all case reports and thus suffer from relevant reporting bias.
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A randomized clinical trial evaluating the immunomodulatory effect of convalescent plasma on COVID-19-related cytokine storm
Pouladzadeh, M., Safdarian, M., Eshghi, P., Abolghasemi, H., Bavani, A. G., Sheibani, B., Moradi Choghakabodi, P., Feghhi, A., Ghafourian Boroujerdnia, M., Forouzan, A., et al
Internal and emergency medicine. 2021;:1-11
Abstract
Evaluating the effect of convalescent plasma (CP) on some cytokine storm indices in severe COVID-19 patients. Totally, 62 patients were randomly assigned into two groups for this clinical trial. Patients in the intervention group received one unit (500 mL) plasma on the admission day plus standard drugs while the controls merely received standard treatments. Eventually, primary and secondary outcomes were evaluated. In the CP group, compared with controls, the mean levels of lymphocytes and IL-10 significantly increased while the levels of IL-6, TNF-α, and IFN-γ decreased (p < 0.05). The length of in-hospital stay, and mortality rate did not significantly reduce in the CP group compared with controls (p > 0.05) while WHO severity scores remarkably improved (p = 0.01), despite the higher frequency of underlying diseases among the CP group (66.7%) vs. controls (33.3%). Although CP has a remarkable immunomodulatory and antiviral potential to improve the cytokine storm and disease severity in COVID-19 patients, it did not considerably affect the mortality rate.
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Correction: Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis
Peng, H. T., Rhind, S. G., Beckett, A.
JMIR Public Health and Surveillance. 2021;7(6):e31554
Abstract
[This corrects the article DOI: 10.2196/25500.].
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10.
Convalescent plasma for COVID-19 in hospitalised patients: an open-label, randomised clinical trial
Sekine, L., Arns, B., Fabro, B. R., Cipolatt, M. M., Machado, R. R. G., Durigon, E. L., Parolo, E., Pellegrini, J. A. S., Viana, M. V., Schwarz, P., et al
The European Respiratory Journal. 2021
Abstract
BACKGROUND The effects of convalescent plasma (CP) therapy hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect CP on clinical improvement in these patients. METHODS This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment. RESULTS A total of 160 (80 in each arm) patients (66.3% were critically ill and 33.7%, severe) completed the trial. The median age was 60.5 years (interquartile range [IQR], 48-68), 58.1% were men and the median time from symptom onset to randomisation was 10 days (IQR, 8-12). Neutralising antibodies titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC and 65.0% in the SOC group (difference, -3.7%; 95% Confidence Interval [CI], -18.8%-11.3%). The results were similar in the subgroups of severe and critically ill. There was no significant difference between CP+SOC and SOC groups in prespecified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratorial markers values on days 3, 7 and 14 were similar between groups. CONCLUSIONS CP+SOC did not result in a higher proportion of clinical improvement on at day 28 in hospitalised patients with COVID-19 compared to SOC alone.
