Early Administration of Convalescent Plasma Improves Survival in Patients with Hematological Malignancies and COVID-19
The use of convalescent plasma in the treatment of COVID-19 may lead to a milder course of infection and has been associated with improved outcomes Determining optimal treatments in high risk populations is crucial, as is the case in those with hematological malignancies We analyzed a cohort of 23 patients with hematological malignancies and COVID-19 who had received plasma 48–72 h after the diagnosis of infection and compared it with a historical group of 22 patients who received other therapy Overall survival in those who received convalescent plasma was significantly higher than in the historical group (p = 0 03460) The plasma–treated group also showed a significantly milder course of infection (p = 0 03807), characterized by less severe symptoms and faster recovery (p = 0 00001) In conclusion, we have demonstrated that convalescent plasma is an effective treatment and its early administration leads to clinical improvement, increased viral clearance and longer overall survival in patients with hematological malignancies and COVID-19 To our knowledge, this is the first report to analyze the efficacy of convalescent plasma in a cohort of patients with hematological malignancies
Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial
Lancet (London, England). 2021
BACKGROUND Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. METHODS This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. FINDINGS Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93-1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94-1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93-1·05; p=0·79). INTERPRETATION In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. FUNDING UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Patients admitted to hospital with COVID-19 and enrolled in the RECOVERY trial (n=11,558).
Convalescent plasma (n= 5,795).
Usual care (n= 5,763).
There was no significant difference in 28-day mortality between the two groups: 1,399 (24%) of patients in the convalescent plasma group and 1,408 (24%) of patients in the usual care group died within 28 days. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days 3,832 (66%) patients in the convalescent plasma group vs. 3,822 (66%) patients in the usual care group. Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death 1,568 (29%) of 5,493 patients in the convalescent plasma group vs. 1,568 (29%) of 5,448 patients in the usual care group.
How should we use convalescent plasma therapies for the management of COVID-19?
Convalescent plasma (CP) from blood donors with antibodies to severe acute respiratory syndrome coronavirus 2 may benefit patients with COVID-19 by providing immediate passive immunity via transfusion or by being used to manufacture hyperimmune immunoglobulin preparations Optimal product characteristics (including neutralizing antibody titers), transfusion volume, and administration timing remain to be determined Preliminary COVID-19 CP safety data are encouraging, but establishing the clinical efficacy of CP requires an ongoing international collaborative effort Preliminary results from large, high-quality randomized trials have recently started to be reported
Current views on the potentials of convalescent plasma therapy (CPT) as Coronavirus disease 2019 (COVID-19) treatment: A systematic review and meta-analysis based on recent studies and previous respiratory pandemics
Reviews in Medical Virology. 2021
Convalescent plasma therapy (CPT) has been investigated as a treatment for COVID-19. This review evaluates CPT in COVID-19 and other viral respiratory diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. PubMed and Google scholar databases were used to collect eligible publications until 8 December 2020. Meta-analysis used Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI) and pooled analysis for individual patient data with inverse variance weighted average. The study is registered at PROSPERO with the number of CRD4200270579. Forty-four studies with 36,716 participants were included in the pooled analysis and 20 studies in the meta-analysis. Meta-analysis showed reduction of mortality (RR 0.57, 95% CI [0.43, 0.76], z = 3.86 [p < 0.001], I(2) = 44% [p = 0.03]) and higher number of discharged patients (RR 2.53, 95% CI [1.72, 3.72], z = 4.70 [p < 0.001], I(2) = 3% [p = 0.39]) in patients receiving CPT compared to standard care alone. A possible mechanism of action is prompt reduction in viral titre. Serious transfusion-related adverse events were reported to be less than 1% of cases, suggesting the overall safety of CPT; nevertheless, the number of patients participating in the studies was still limited. It is also important to notice that in all the studies, the majority of patients were also given other medications, such as antivirals, antibiotics and corticosteroid; furthermore, randomized controlled studies involving more patients and in combination with other treatment modalities are urgently needed.
Treatment of COVID-19 patients using plasma therapy
Journal of Birjand University of Medical Sciences. 2021;28(1):84-87
The symptoms of COVID-19, caused by the newly known type of coronavirus, vary widely from asymptomatic, mild to severe respiratory infection leading to hospitalization or death of patients To date, no specific drug has been reported for the treatment of patients affected by this virus One of the approaches adopted for the treatment of this disease is the use of plasma therapy, which contains antibodies against the virus Following of the plasma therapy have not been reported any serious side effects Currently, the numbers of these studies are limited, and evaluation of the larger population studies can provide stronger evidence for treating physicians about the effectiveness of this therapeutic approach [ABSTRACT FROM AUTHOR] Copyright of Journal of Birjand University of Medical Sciences is the property of Birjand University of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )
Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease
Scientific reports. 2021;11(1):9927
Convalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22-2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.
Immunomodulatory therapies for SARS-CoV-2 infection: a systematic literature review to inform EULAR points to consider
Annals of the rheumatic diseases. 2021
OBJECTIVE To summarise the available information on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection. METHODS As part of a European League Against Rheumatism (EULAR) taskforce, a systematic literature search was conducted from January 2019 to 11 December 2020. Two reviewers independently identified eligible studies according to the Population, Intervention, Comparator and Outcome framework and extracted data on efficacy and safety of immunomodulatory agents used therapeutically in SARS-CoV-2 infection at any stage. The risk of bias was assessed with validated tools. RESULTS Of the 60 372 records, 401 articles were eligible for inclusion. Studies were at variable risk of bias. Randomised controlled trials (RCTs) were available for the following drugs: hydroxychloroquine (n=12), glucocorticoids (n=6), tocilizumab (n=4), convalescent plasma (n=4), interferon beta (n=2), intravenous immunoglobulins (IVIg) (n=2) and n=1 each for anakinra, baricitinib, colchicine, leflunomide, ruxolitinib, interferon kappa and vilobelimab. Glucocorticoids were able to reduce mortality in specific subsets of patients, while conflicting data were available about tocilizumab. Hydroxychloroquine was not beneficial at any disease stage, one RCT with anakinra was negative, one RCT with baricitinib+remdesivir was positive, and individual trials on some other compounds provided interesting, although preliminary, results. CONCLUSION Although there is emerging evidence about immunomodulatory therapies for the management of COVID-19, conclusive data are scarce with some conflicting data. Since glucocorticoids seem to improve survival in some subsets of patients, RCTs comparing glucocorticoids alone versus glucocorticoids plus anticytokine/immunomodulatory treatment are warranted. This systematic literature review informed the initiative to formulate EULAR 'points to consider' on COVID-19 pathophysiology and immunomodulatory treatment from the rheumatology perspective.
Correlation of Automated Chemiluminescent Method with Enzyme-Linked Immunosorbent Assay (ELISA) Antibody Titers in Convalescent COVID-19 Plasma Samples: Development of Rapid, Cost-Effective Semi-Quantitative Diagnostic Methods
Journal of Blood Medicine. 2021;12:157-164
Background: We investigated the utility of an automated chemiluminescent SARS-CoV-2 IgG antibody assay platform in quantifying the amount of binding antibodies present in donated convalescent plasma Methods: A total of 179 convalescent plasma units were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Beckman-Coulter chemiluminescent immunoassay (CLIA) platform The equipment-derived numerical values (S/Co ratio) were recorded Aliquots from the same units were subjected to enzyme-linked immunosorbent assay (ELISA) that detects IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 S1 protein The relationship between ELISA titers and CLIA S/Co values was analyzed using linear regression and receiver operating characteristics (ROC) curve Results: Twenty-one samples (11 7%) had S/Co values of less than 1 0 and were deemed negative for antibodies and convalescent plasma had S/Co values between > 1 0 and 5 0 (70/179, 39 1%) Fifteen units (8 4%) had negative ELISA titer The majority of the units (95/179 53 1%) had titers ≥ 1:1024 The sensitivities of ELISA to CLIA were comparable (90 5% vs 88 3%, respectively;p=0 18) There was positive linear correlation between CLIA S/Co values and ELISA IgG titer (Rho = 0 75;Spearman’s rank = 0 82, p-value = < 0 0001) The agreement between the two methods was fair, with a κ index of 0 2741 Using the ROC analysis, we identified a CLIA S/Co cutoff value of 8 2, which gives a sensitivity of 90% and a specificity of 82% in predicting a titer dilution of ≥ 1:1024 Conclusion: The utility of automated antibody detection systems can be extended from simply a screening method to a semi-quantitative and quantitative functional antibody analysis CLIA S/Co values can be used to reliably estimate the ELISA antibody titer Incorporation of chemiluminescent-based methods can provide rapid, cost-effective means of identifying anti-SARS-CoV-2 antibody titers in donated plasma for use in the treatment of COVID-19 infection
Effects and Safety of Convalescent Plasma Administration in a Group of Polish Pediatric Patients with COVID-19: A Case Series
Despite the enormous advances in knowledge about the SARS-CoV-2 infection, the optimal treatment for COVID-19 is still not well defined The use of convalescent plasma seems to be a promising method of treatment but requires further evaluation Although it is usually mild, in children with underlying chronic diseases, the course of SARS-CoV-2 infection may be very severe We described a series of 13 pediatric patients (mean age 10 4 years, median 12) treated with convalescent plasma as a method of COVID-19 therapy Medical history, with particular emphasis on comorbidities, clinical course, laboratory parameters, supportive treatment and virus elimination time, were analyzed The mean hospitalization time was 22 6 days (median 20) The most common abnormalities included increased levels of C-reactive protein, D-dimer, and lymphopenia Median time from symptom onset to convalescent plasma transfusion was 10 6 days (median 7 days) Six patients (46 2%) had a viral clearance on RT-PCR method from a nasopharyngeal swab within 3 days of transfusion, while in the remaining patients the mean elimination time was 12 1 days (median 6 days) Clinical improvement was achieved in all patients;no adverse effects were found in any of the cases Convalescent plasma may be a promising treatment for COVID-19 in children
Peripheral Blood Immune Profiling of Convalescent Plasma Donors Reveals Alterations in Specific Immune Subpopulations Even at 2 Months Post SARS-CoV-2 Infection
Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e g , lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects were analyzed by multiparametric flow cytometry, allowing the identification of a wide panel of immune cells, comprising lymphocytes (T, B, natural killer (NK) and NKT cells), monocytes, granulocytes, and their subsets Compared to active COVID-19 patients, our results revealed that the immune profile of recovered donors was restored for most subpopulations Nevertheless, even 2 months after recovery, CP donors still had reduced levels of CD4+ T and B cells, as well as granulocytes CP donors with non-detectable levels of anti-SARS-CoV-2-specific antibodies in their serum were characterized by higher Th9 and Th17 cells, which were possibly expanded at the expense of Th2 humoral immunity The most noticeable alterations were identified in previously hospitalized CP donors, who presented the lowest levels of CD8+ regulatory T cells, the highest levels of CD56+CD16−NKT cells, and a promotion of a Th17-type phenotype, which might be associated with a prolonged pro-inflammatory response A longer follow-up of CP donors will eventually reveal the time needed for full recovery of their immune system competence