Convalescent Plasma Therapy for COVID-19 in Ambulatory vs Hospitalized Patients: Efficacy and Risk of Thromboembolism
Research and practice in thrombosis and haemostasis. 2023;:100068
BACKGROUND While early evidence concluded a lack of clinical benefit of convalescent plasma therapy (CPT) in COVID-19 management, recent trials demonstrate the therapeutic potential of CPT in ambulatory care. CPT may also potentiate thromboembolic events given the presence of coagulation factors and the prothrombotic state of COVID-19. OBJECTIVE The present study aims to assess and compare the clinical efficacy and the risk of venous/arterial thromboembolism (VTE, ATE) of CPT in ambulatory vs hospitalized COVID-19 patients. METHODS MEDLINE, Embase, and Cochrane CENTRAL were searched from December 2019 to December 2022 for randomized controlled trials that investigated the use of CPT against placebo or standard of care in adult COVID-19 patients. The primary outcome was non-mortality disease progression. Secondary outcomes include VTE, ATE, 28-day mortality, clinical improvement, length of hospitalization (LOH), sepsis/fever, and major adverse cardiovascular events (MACE). RESULTS Twenty randomized controlled trials, with 21340 patients, were included. CPT significantly reduced non-mortality disease progression in ambulatory patients (OR 0.72, 0.56-0.92, P = 0.009) but not in hospitalized patients (1.03, 0.94-1.12, P = 0.58). The risk of VTE and ATE did not differ between the CPT and the control group (1.15, 0.81 to 1.64, P = 0.44; 1.01, 0.37 to 2.79, P = 0.98). No conclusive differences between CPT and control were noted in 28-day mortality, clinical improvement, LOH, risk of sepsis/fever, and MACE. CONCLUSIONS In conclusion, treatment of COVID-19 with CPT prevents the progression of COVID-19 in the ambulatory care. It is not associated with an increased risk of VTE, ATE, or other adverse events.
Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis
Mayo Clinic proceedings. Innovations, quality & outcomes. 2023;7(5):499-513
OBJECTIVE To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. PATIENTS AND METHODS On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. RESULTS Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). CONCLUSION During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.
Effect of convalescent plasma transfusion on outcomes of coronavirus disease 2019: a meta-analysis with trial sequential analysis
Journal of anesthesia. 2023;:1-14
The aim of this review was to update evidence for benefit of convalescent plasma transfusion (CPT) in patients with coronavirus disease 2019 (COVID-19). Databases were searched for randomized controlled trials (RCT) comparing CPT plus standard treatment versus standard treatment only in adults with COVID-19. Primary outcome measures were mortality and need for invasive mechanical ventilation (IMV). Twenty-Six RCT involving 19,816 patients were included in meta-analysis for mortality. Quantitative synthesis showed no statistically significant benefit of adding CPT to standard treatment (RR = 0.97, 95% CI = 0.92 to 1.02) with unimportant heterogeneity (Q(25) = 26.48, p = .38, I(2) = 0.00%). Trim-and-fill-adjusted effect size was unimportantly changed and level of evidence was graded as high. Trial sequential analysis (TSA) indicated information size was adequate and CPT was futile. Seventeen trials involving 16,083 patients were included in meta-analysis for need of IMV. There was no statistically significant effect of CPT (RR = 1.02, 95% CI = 0.95 to 1.10) with unimportant heterogeneity (Q(16) = 9.43, p = .89, I(2) = 3.30%). Trim-and-fill-adjusted effect size was trivially changed and level of evidence was graded as high. TSA showed information size was adequate and indicated futility of CPT. It is concluded with high level of certainty that CPT added to standard treatment of COVID-19 is not associated with reduced mortality or need of IMV compared with standard treatment alone. In view of these findings, further trials on efficacy of CPT in COVID-19 patients are probably not needed.
Overlapping research efforts in a global pandemic: a rapid systematic review of COVID-19-related individual participant data meta-analyses
BMC health services research. 2023;23(1):735
BACKGROUND Individual participant data meta-analyses (IPD-MAs), which involve harmonising and analysing participant-level data from related studies, provide several advantages over aggregate data meta-analyses, which pool study-level findings. IPD-MAs are especially important for building and evaluating diagnostic and prognostic models, making them an important tool for informing the research and public health responses to COVID-19. METHODS We conducted a rapid systematic review of protocols and publications from planned, ongoing, or completed COVID-19-related IPD-MAs to identify areas of overlap and maximise data request and harmonisation efforts. We searched four databases using a combination of text and MeSH terms. Two independent reviewers determined eligibility at the title-abstract and full-text stages. Data were extracted by one reviewer into a pretested data extraction form and subsequently reviewed by a second reviewer. Data were analysed using a narrative synthesis approach. A formal risk of bias assessment was not conducted. RESULTS We identified 31 COVID-19-related IPD-MAs, including five living IPD-MAs and ten IPD-MAs that limited their inference to published data (e.g., case reports). We found overlap in study designs, populations, exposures, and outcomes of interest. For example, 26 IPD-MAs included RCTs; 17 IPD-MAs were limited to hospitalised patients. Sixteen IPD-MAs focused on evaluating medical treatments, including six IPD-MAs for antivirals, four on antibodies, and two that evaluated convalescent plasma. CONCLUSIONS Collaboration across related IPD-MAs can leverage limited resources and expertise by expediting the creation of cross-study participant-level data datasets, which can, in turn, fast-track evidence synthesis for the improved diagnosis and treatment of COVID-19. TRIAL REGISTRATION 10.17605/OSF.IO/93GF2.
Convalescent plasma and all-cause mortality of COVID-19 patients: systematic review and meta-analysis
Scientific reports. 2023;13(1):12904
Insight into the clinical potential of convalescent plasma in patients with coronavirus disease (COVID-19) is important given the severe clinical courses in unvaccinated and seronegative individuals. The aim of the study was to investigate whether there is a survival benefit of convalescent plasma therapy in COVID-19 patients. The authors independently assessed randomized controlled trials (RCTs) identified by the search strategy for inclusion, extracted data, and assessed risk of bias. The binary primary outcome was all-cause mortality. Risk ratio (RR) of the convalescent plasma treatment (vs. best standard care) and its associated standard error (effect size) were calculated. A random-effects model was employed to statistically pool the effect sizes of the selected studies. We included 19 RCTs with 17,021 patients. The random-effects model resulted in an estimated pooled RR of 0.94 (95% CI 0.81-1.08, p = 0.33), showing no statistical evidence of the benefit of convalescent plasma therapy on all-cause mortality. Convalescent plasma therapy was not found to be effective in reducing all-cause mortality in COVID-19 patients. Further studies are needed to determine in which patients convalescent plasma therapy may lead to a reduction in mortality.
Convalescent Plasma Therapy for COVID-19: A Systematic Review and Meta-Analysis on Randomized Controlled Trials
Background: While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess the role of convalescent plasma treatment on the clinical outcomes of COVID-19 patients enrolled in randomized controlled trials (RCTs). Methods: A systematic search was conducted in the PubMed database (end-of-search: 29 December 2022) for RCTs on convalescent plasma therapy compared to supportive care\standard of care. Pooled relative risk (RR) and 95% confidence intervals were calculated with random-effects models. Subgroup and meta-regression analyses were also performed, in order to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 34 studies were included in the meta-analysis. Per overall analysis, convalescent plasma treatment was not associated with lower 28-day mortality [RR = 0.98, 95% CI (0.91, 1.06)] or improved 28-day secondary outcomes, such as hospital discharge [RR = 1.00, 95% CI (0.97, 1.03)], ICU-related or score-related outcomes, with effect estimates of RR = 1.00, 95% CI (0.98, 1.05) and RR = 1.06, 95% CI (0.95, 1.17), respectively. However, COVID-19 outpatients treated with convalescent plasma had a 26% less risk of requiring hospital care, when compared to those treated with the standard of care [RR = 0.74, 95% CI (0.56, 0.99)]. Regarding subgroup analyses, COVID-19 patients treated with convalescent plasma had an 8% lower risk of ICU-related disease progression when compared to those treated with the standard of care (with or without placebo or standard plasma infusions) [RR = 0.92, 95% CI (0.85, 0.99)] based on reported outcomes from RCTs carried out in Europe. Finally, convalescent plasma treatment was not associated with improved survival or clinical outcomes in the 14-day subgroup analyses. Conclusions: Outpatients with COVID-19 treated with convalescent plasma had a statistically significantly lower risk of requiring hospital care when compared to those treated with placebo or the standard of care. However, convalescent plasma treatment was not statistically associated with prolonged survival or improved clinical outcomes when compared to placebo or the standard of care, per overall analysis in hospitalized populations. This hints at potential benefits, when used early, to prevent progression to severe disease. Finally, convalescent plasma was significantly associated with better ICU-related outcomes in trials carried out in Europe. Well-designed prospective studies could clarify its potential benefit for specific subpopulations in the post-pandemic era.
The use of Platelet rich Plasma in COVID-19 Induced Olfactory Dysfunction: Systematic Review
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2023;:1-5
PURPOSE Different modalities of treatment have been suggested in the treatment for post COVID-19 olfactory dysfunction (OD). Starting with lifestyle modification, smoking cessation, for example, was shown to improve the symptoms for patients with OD. Intranasal and oral corticosteroids have been described in the literature for the treatment of OD. In this review, we are looking at a novel intervention using platelet-rich plasma injection into the nasal cleft for treatment of post COVID-19 infection olfactory dysfunction. METHODS A literature search was done using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 Guidelines, the databases of PMC, Medline, CINAHL, Wiley online library were searched from their year of inception until February 2023. Search terms were used and included a combination of the following keywords; "platelet-rich plasma", "platelet rich plasma", "PRP", "Anosmia", "olfactory dysfunction" and "COVID". RESULTS The four studies in this review included a total of 238 adult patients who presented with olfactory dysfunction. The studies were heterogenic in terms of follow up period which was not long enough through all the included studies. Additionally, different protocol of injecting was seen in different studies. CONCLUSION Injecting PRP for treatment of COVID-19 induced olfactory dysfunction is a safe technique with what seems like promising initial results with low complication rate. However, there are not enough studies assessing its effectiveness compared to other treatment modalities. Further randomized controlled trials with shared protocol are needed to establish further understanding of its role in treatment of COVID-19 induced OD.
COVID-19 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-analysis of Individual Participant Data From Five Randomized Trials
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023
BACKGROUND Outpatient monoclonal antibodies are no longer effective and antiviral treatments for COVID-19 disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma is promising, clinical trials among outpatients have shown mixed results. METHODS We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching MEDLINE, Embase, MedRxiv, World Health Organization, Cochrane Library, and Web of Science from January 2020 to September 2022. RESULTS Five included studies from four countries enrolled and transfused 2,620 adult patients. Comorbidities were present in 1,795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1315 control patients were hospitalized, versus 111 (8.5%) of 1305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95%CI: 1.3%-6.0%; p=.001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95%CI: 4.0%-11.1%; p=.0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving COVID-19 convalescent plasma with antibody titers below the median titer. CONCLUSIONS Among outpatients with COVID-19, treatment with COVID-19 convalescent plasma reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.
Adult COVID-19 outpatients (5 studies, n= 2,620).
Intravenous COVID-19 convalescent plasma (CCP) transfusion (n= 1,305).
Non-convalescent plasma or normal saline (n= 1,315).
The virus neutralizing antibody dilutional titre levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1,315 control patients were hospitalized, versus 111 (8.5%) of 1,305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95% CI: 1.3% - 6.0%) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titre with a 7.6% absolute risk reduction (95% CI: 4.0% - 11.1%) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving COVID-19 convalescent plasma with antibody titres below the median titre.
Platelet-rich plasma for the treatment of COVID-19 related olfactory dysfunction: a systematic review
INTRODUCTION Olfactory Dysfunction (OD) is a prevalent issue with a significant number of cases attributed to COVID-19. This systematic review aimed to evaluate the effectiveness of platelet-rich plasma (PRP) in the treatment of COVID-19 related OD, including anosmia, hyposmia, and parosmia. METHODS A comprehensive literature search was conducted using Medline, Scopus, Directory of Open Access Journals (DOAJ), and Google Scholar from inception until December 22, 2022. The eligibility criteria were confirmed COVID-19 patients with OD, whether it was measured objectively and/or subjectively, who received PRP treatment. The study followed a pre-specified protocol registered in PROSPERO (ID: CRD42023386803) and adhered to PRISMA guidelines. RESULTS Four studies that enrolled 233 patients were included. The degree of improvement was assessed using threshold-discrimination-identification (TDI) scores at baseline and 1 and 2 months after PRP injection. Parosmia was assessed using the Visual Analog Scale (VAS) scores. Treatment of OD with PRP injections resulted in variable degrees of improvement. However, PRP injections can be considered safe, effective, and promising therapeutic options, as revealed by pooled studies. CONCLUSIONS This systematic review indicated that PRP may be an effective treatment for COVID-19 related OD. However, additional large-scale studies are required to further investigate PRP efficacy in the treatment of OD following COVID-19.
Clinical nursing care protocol for convalescent plasma transfusion in patients with COVID-19
International journal of Africa nursing sciences. 2023;18:100518
INTRODUCTION The treatment of COVID-19 is still challenge. So convalescent plasma can be an important alternative of treatment. Protocols with nursing care during infusion is very important to guide an effective and safety care. OBJECTIVE to analyze the evidence in the literature on the action of convalescent plasma, of the use of protocols with nursing care to use convalescent plasma and build a nursing care protocol for transfusion in patients with COVID-19. METHODS Methodological study carried out in two stages: scoping review. The search was done using the descriptors: convalescent plasma transfusion, convalescent plasma, and acute respiratory syndromes or COVID-19, to found protocols and effectiveness of convalescent plasm. Beside was done a specialist panel to build the protocol. RESULTS Low-evidence studies have shown improvement in the clinical signs of COVID-19 using Convalescent Plasma, reduction or elimination of viral load, benefits in the production of lymphocytes, decreases C-reactive protein, increases titers of anti-SARS-CoV-2 antibodies, positive evolution in lung involvement identified by X-rays, decrease in hospitalization. No studies were found in the databases on the protocol for clinical nursing care in plasma transfusion. Therefore, a protocol was developed with the description of clinical nursing care to be performed before, during and after the transfusion by plasma: checking of vital signs and indicative signs of transfusion reaction, measurement of oxygen saturation, assessment of venous access and checking of the level of consciousness. CONCLUSION There are no evidence studies to support the use of plasma, nor anything related to bundles.