Convalescent Plasma Treatment Research Articles

Development and Validation of a Treatment Benefit Index to Identify Hospitalized Patients With COVID-19 Who May Benefit From Convalescent Plasma

Identifying which patients with COVID-19 are likely to benefit from COVID-19 convalescent plasma (CCP) treatment may have a large public health impact. To develop an index for predicting the expected relative treatment benefit from CCP compared with treatment without CCP for patients hospitalized for COVID-19 using patients' baseline characteristics. This prognostic study used data from the COMPILE study, ie, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) evaluating CCP vs control in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. A combination of baseline characteristics, termed the treatment benefit index (TBI), was developed based on 2287 patients in COMPILE using a proportional odds model, with baseline characteristics selected via cross-validation. The TBI was externally validated on 4 external data sets: the Expanded Access Program (1896 participants), a study conducted under Emergency Use Authorization (210 participants), and 2 RCTs (with 80 and 309 participants). Receipt of CCP. World Health Organization (WHO) 11-point ordinal COVID-19 clinical status scale and 2 derivatives of it (ie, WHO score of 7-10, indicating mechanical ventilation to death, and WHO score of 10, indicating death) at day 14 and day 28 after randomization. Day 14 WHO 11-point ordinal scale was used as the primary outcome to develop the TBI. A total of 2287 patients were included in the derivation cohort, with a mean (SD) age of 60.3 (15.2) years and 815 (35.6%) women. The TBI provided a continuous gradation of benefit, and, for clinical utility, it was operationalized into groups of expected large clinical benefit (B1; 629 participants in the derivation cohort [27.5%]), moderate benefit (B2; 953 [41.7%]), and potential harm or no benefit (B3; 705 [30.8%]). Patients with preexisting conditions (diabetes, cardiovascular and pulmonary diseases), with blood type A or AB, and at an early COVID-19 stage (low baseline WHO scores) were expected to benefit most, while those without preexisting conditions and at more advanced stages of COVID-19 could potentially be harmed. In the derivation cohort, odds ratios for worse outcome, where smaller odds ratios indicate larger benefit from CCP, were 0.69 (95% credible interval [CrI], 0.48-1.06) for B1, 0.82 (95% CrI, 0.61-1.11) for B2, and 1.58 (95% CrI, 1.14-2.17) for B3. Testing on 4 external datasets supported the validation of the derived TBIs. The findings of this study suggest that the CCP TBI is a simple tool that can quantify the relative benefit from CCP treatment for an individual patient hospitalized with COVID-19 that can be used to guide treatment recommendations. The TBI precision medicine approach could be especially helpful in a pandemic.

Association of Convalescent Plasma Treatment With Clinical Status in Patients Hospitalized With COVID-19

COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing. To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP. From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly. Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally. A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board. Prespecified coprimary end points-the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model-were assessed clinically at 14 days after randomization. Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics. This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.

LESSONS AND NEW PERSPECTIVES: IS CONVALESCENT PLASMA THERAPY EFFECTIVE ON COVID-19 PATIENTS?

Objective: Recently, convalescent plasma (CP) therapy has shown promising evidence in the treatment of several serious contagious diseases, including SARS-CoV, Influenza and Ebola. We conducted a systematic review to extract data about using CP treatment for COVID-19 patients and it’s effectively. Methods: The retrieval of studies was conducted according to Cochrane Collaboration and from electronic databases including PubMed, Medline, and others (medRxiv and BioRxiv). Searching of the available evidence concerning CP treatment of COVID-19 patients was conducted in journal articles published between December 2019 and October 2020. The articles were further screened based on inclusion and exclusion criteria to identify the high-quality studies for analysis. Results: A total of 18 CP studies were included in this review. We found variance regarding the effectiveness of CP in the reduction of mortality rate, length of stay, and increased discharging rate. Several findings show CP therapy is effective in increasing viral negativity, neutralizing antibodies to recipients, does not cause harmful adverse reactions and in some cases can improve clinical symptoms. This therapy is presently considered effective for generating good clinical outcomes when given early in the course of the disease. Conclusion: The effectiveness of CP in terms of mortality, length of stay, and increased discharging patients is still debatable. However, CP therapy is effective in increasing the negativity of SARS-CoV-2 test, neutralizing antibody titer and is safe so it can be considered for COVID-19 patients. CP should not be given in the initial disease course but is recommended for the early disease course.

Propensity score-matched case–control study of convalescent plasma in treatment of patients with moderate and severe COVID-19

Background: Convalescent plasma (CP) in coronavirus disease 2019 (COVID-19) acts as a source of neutralizing antibodies that could provide passive immunity. There still exists uncertainty on the safety and efficacy of CP as a therapeutic option in COVID-19. This study reports on the effectiveness of CP therapy (CPT) in patients with moderate and severe COVID-19 in an Indian cohort. Methodology: This propensity score matched (PSM) case–control study included a total of 477 adult patients with COVID-19 (≥18 years of age) with moderate and severe disease out of which 181 patients received CP having neutralizing antibody titers ≥1:40 (PRNT/MNT). PSM with an optimal algorithm was performed, matching cases (CP recipients) on baseline patient characteristics to select (178) controls in a 1:1 ratio. Analysis included logistic regression for the whole-patient sample, conditional logistic regression for PSM sample, and competing risk approach for time-to-event analysis. Primary outcome was in-hospital all-cause mortality. Results: Greater odds of clinical improvement were observed among CP recipients on day 7, but no significant differences were observed in the clinical status on day 14. Mortality was lower in patients treated with CP; however, the difference was not statistically significant. Logistic-regression analysis for whole-patient sample and conditional logistic regression for PSM sample showed no significant mortality benefit of CP both in the unadjusted and covariate-adjusted models. No significant mortality benefit was observed among CP recipients in the survival analysis. Conclusion: CPT in COVID-19 appears to have some benefit as evinced by greater odds of clinical recovery on day 7, however, offers no survival benefit.

An evaluation of the results of convalescent plasma therapy applied to pregnant women diagnosed as COVID-19- positive in a pandemic center: A prospective cohort study.

Convalescent plasma (CP) might be an additional treatment modality in COVID-19. The aim of this study was to compare CP-related clinical characteristics and perinatal outcomes in pregnant women with mild or moderate-severe COVID-19. This prospective cohort study included 36 pregnant women (12 mild and 24 moderate-severe), who underwent CP therapy. The CP obtained from recently recovered donors was transfused to patients together with maximum supportive care and antiviral agents. The groups were then compared in respect of clinical characteristics, laboratory parameters, obstetric complications, and neonatal outcomes. Significant differences were determined between the groups in respect of systemic corticosteroids in COVID-19 treatment (41.7%, 87.5%, p = 0.004), oxygen (O2) support (0%, 91.7%, p &lt; 0.001), chest imaging (41.7%, 58.3%, p = 0.02), intensive care unit admission (0%, 20.8%, p = 0.03) and length of hospitalization (5.5 versus 9.5 days, p &lt; 0.001). The O2 saturation levels before and after administration of CP were significantly lower in the moderate-severe COVID-19 group (p &lt; 0.05). The O2 therapy time before and after administration of CP and total O2 therapy time were significantly lower in the mild COVID-19 group (p &lt; 0.05). Platelet, plateletcrit and lymphocyte counts were significantly higher in both the mild and moderate-severe COVID-19 groups after treatment compared to the pretreatment values (p &lt; 0.05). Although data on the results of CP treatment in pregnant women are somewhat limited, it has been suggested that early CP treatment may be associated with improvements in laboratory and ventilatory parameters in pregnant women with mild and moderate-severe COVID-19. Nevertheless, there is a need for further, randomized controlled studies on this subject with the inclusion of greater numbers of patients.

Comparison of the Effectiveness of Early and Late Convalescent Plasma Treatment Given in Patients Diagnosed with Coronavirus Disease in Intensive Care Unit

Comparison of the Effectiveness of Early and Late Convalescent Plasma Treatment Given in Patients Diagnosed with Coronavirus Disease in Intensive Care Unit

The Effect of Convalescent Plasma in Patients With Covid-19 in Intensive Care Unit.

Convalescent plasma collected from COVID-19 survivors contains antibodies against receptor binding domains with potent antiviral activity. The use of this therapy for COVID-19 is still under investigation, as the pathophysiological and immunological mechanisms responsible for the evolution of the disease have not been fully identified. In this retrospective observational study, we included all patients with a confirmed SARS-Cov-2 infection based on positive RT-PCR testing, who received convalescent plasma treatment in addition to standard therapy, between 17.05.2020 and 27.11.2020, following hospitalization in the Anaesthesia and Intensive Care Unit of the Sibiu County Emergency Clinical Hospital, Romania. Convalescent plasma therapy of patients with SARS-Cov-2 infection and severe forms of the disease (requiring only high-flow oxygen therapy or non-invasive ventilation) significantly improved inflammatory markers (CRP, fibrinogen) and ventilatory parameters (SaO2, paO2, paO2/FiO2) reducing the need of supplemental oxygen delivery (p<0.05). Other factors that had a significant influence on the outcome were age and comorbidity. Inflammatory markers and ventilatory parameters were significantly improved and the need of supplemental oxygen delivery was reduced in COVID-19 patients treated with convalescent plasma.

On the Safety of the COVID-19 Convalescent Plasma Treatment: Thrombotic and Thromboembolic Concerns

Recently, it was reported that near-sourced COVID-19 convalescent plasma (CP) is more efficient than distantly sourced CP. What was left behind in this analysis is the investigation of the possible causes of mortality associated with the CP transfusion itself. Knowing this information is important for determining whether not receiving CP of near source is the main cause of high rate of death in the group of patients who received distantly sourced CP. We argue that the thrombotic and thromboembolic events may act as risk factors for adverse complications and death associated with CP transfusion. Therefore, they have to be considered and carefully accounted for in population studies as they can affect the CP safety profiles and change the interpretation of the cause of death in the studied groups.

Case Series: Convalescent Plasma Therapy for Patients with COVID-19 and Primary Antibody Deficiency

Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.

Convalescent plasma treatment in severely immunosuppressed patients hospitalized with COVID-19: an observational study of 28 cases

Background Immunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who were all treated with convalescent plasma (CCP) along with standard treatment. Methods We performed an observational, retrospective case series between May 2020 to March 2021 at three sites in Skåne, Sweden, with a population of nearly 1.4 million people. All patients hospitalized for COVID-19 who received CCP with the indication severe immunosuppression as defined by the treating physician were included in the study (n = 28). Results In total, 28 severely immunocompromised patients, half of which previously had been treated with rituximab, who had received in-hospital convalescent plasma treatment of COVID-19 were identified. One week after CCP treatment, 13 of 28 (46%) patients had improved clinically defined as a decrease of at least one point at the WHO-scale. Three patients had increased score points of whom two had died. For 12 patients, the WHO-scale was unchanged. Conclusion As one of only few studies on CCP treatment of COVID-19 in hospitalized patients with severe immunosuppression, this study adds descriptive data. The study design prohibits conclusions on safety and efficacy, and the results should be interpreted with caution. Prospective, randomized trials are needed to investigate this further.

675. Crimean-Congo Hemorrhagic Fever Beyond Ribavirin: A Systematic Review

BackgroundThe Crimean-Congo Hemorrhagic Fever (CCHF) is a tick-borne virus infection that has been reported in about 30 countries worldwide. Clinical presentation is divided into three phases: pre-hemorrhagic, hemorrhagic, and convalescence. Ribavirin is standard of care treatment for acute infection and prophylaxis. However, the use of other treatments beyond ribavirin is largely unknown.MethodsWe conducted a systematic review using MOOSE protocol. The inclusion and exclusion criteria are seen in the Prisma diagram. For Bias Analysis we use a Robin-1 tool. Literature review algorithm ResultsWe gathered a total of 10 studies, which included 4 therapeutic plasma exchange (TPE), 2 corticosteroids, 2 IVIG, and 1 with convalescent plasma (CP).TPE in one study showed decreased mortality rate and increased efficacy in patients with severe CCHF. While the other study reported pulmonary embolism related to the use of TPE. Nevertheless, the patients had good outcome in the end. Two case reports used TPE plus ribavirin and supportive measures. Both were discharged home and recovered without sequela. Corticosteroids were found to be beneficial in one study were the case fatality rate was lower with the addition of corticosteroids to ribavirin in severely ill patients (p=0.0014). In a case series of six patients, who received the combination in early stages of the disease had good clinical outcomes with improved survival. IVIG was shown to increase platelet counts in two studies. In the first study, platelet count increased above 150,000/mL in 8.5 +/- 2.5 days. While in the other study the normalization of platelets was seen in 4 - 4.8 days, with no significant difference (P = 0.49). In addition, there was a decrease in the duration of symptoms but there was no statistically significant difference in mortality rates (P = 0.171). CP treatment showed a survival rate of 86% in treated patients. CP was more useful in high-risk patients, defined as having a viral load of 108 copies/mL or more. The main limitations of the studies were the sample size and heterogenicity among the outcomes of the studies. ConclusionTPE, CP, IVIG, and corticosteroids were effective in improving the clinical outcomes of the patients. The use of these treatments beyond ribavirin should be explored in future studies. Disclosures All Authors: No reported disclosures

Persistent SARS-CoV-2 infection in patients with secondary antibody deficiency: successful clearance following combination casirivimab and imdevimab (REGN-COV2) monoclonal antibody therapy

BackgroundThere is growing evidence that antibody responses play a role in the resolution of SARS-CoV-2 infection. Patients with primary or secondary antibody deficiency are at increased risk of persistent infection. This challenging clinical scenario is associated with adverse patient outcome and potentially creates an ecological niche for the evolution of novel SARS-CoV-2 variants with immune evasion capacity. Case reports and/or series have implied a therapeutic role for convalescent plasma (CP) to secure virological clearance, although concerns have been raised about the effectiveness of CP and its potential to drive viral evolution, and it has largely been withdrawn from clinical use in the UK.Case presentationWe report two cases in which persistent SARS-CoV-2 infection was cleared following administration of the monoclonal antibody combination casirivimab and imdevimab (REGN-COV2, Ronapreve). A 55-year-old male with follicular lymphoma, treated with B cell depleting therapy, developed SARS-CoV-2 infection in September 2020 which then persisted for over 200 days. He was hospitalised on four occasions with COVID-19 and suffered debilitating fatigue and malaise throughout. There was no clinical response to antiviral therapy with remdesivir or CP, and SARS-CoV-2 was consistently detected in nasopharyngeal swabs. Intrahost evolution of several spike variants of uncertain significance was identified by viral sequence analysis. Delivery of REGN-COV2, in combination with remdesivir, was associated with clinical improvement and viral clearance within 6 days, which was sustained for over 150 days despite immunotherapy for relapsed follicular lymphoma. The second case, a 68-year-old female with chronic lymphocytic leukaemia on ibrutinib, also developed persistent SARS-CoV-2 infection. Despite a lack of response to remdesivir, infection promptly cleared following REGN-COV2 in combination with remdesivir, accompanied by resolution of inflammation and full clinical recovery that has been maintained for over 290 days.ConclusionsThese cases highlight the potential benefit of REGN-COV2 as therapy for persistent SARS-CoV-2 infection in antibody deficient individuals, including after failure of CP treatment. Formal clinical studies are warranted to assess the effectiveness of REGN-COV2 in antibody-deficient patients, especially in light of the emergence of variants of concern, such as Omicron, that appear to evade REGN-COV2 neutralisation.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

BackgroundConvalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX).MethodsIn this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence.ResultsA total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.ConclusionsConvalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Clinical Outcomes of Convalescent Plasma Transfusion Therapy in Moderate to Critically Ill Covid-19 Patients: A Systematic Review and Meta-Analysis

Background: Currently, Convalescent plasma (CP)is considered a favorable treatment option for moderate to critically ill Covid-19 patients. But there were very few systematic reviews focused on the effect of CP on clinical parameters. As a result, we undertook this systematic review to learn more about the safety and clinical benefits of convalescent plasma therapy over standard treatment (control).&#x0D; Methodology: We searched Pub Med, Embase and other bibliographic databases to find relevant articles between December 2019 and February 2021 and identified 10 relevant articles which compared CP therapy taken in addition to standard medication with the Control group(who received standard medication). Two independent reviewers examined all full-text articles and extracted the required information intoa predesigned proforma. Forest plots were drawn using RevMan v.5, a statistical tool offered by the Cochrane database to estimate the pooled effect.&#x0D; Results: The results of meta-analysis using a random effect model indicated a significant reduction in mortality rate in CP (about 27% risk reduction), a reduced length of hospital stay in about 2 days (Weighted Mean Difference: -2.53, 95% CI, -7.20 to -2.14, P&lt;0.0001), less time to improve clinical symptoms in about 4 days (pooled mean; CP:10.82 days vs Control:15.14 days). C-Reactive Protein (CRP) concentration levels (mg/L) were well controlled with the control group than the CP group and significant changes in lymphocytes and D-dimer values were not observed after CP treatment. It was also found that no difference between CP transfusion and control was seen in improving the oxygen saturationlevels.&#x0D; Conclusion: CP transfusion can be considered safe and showed a significant reduction in mortality and possible benefits in clinical improvement. Patients on CP therapy had no significant benefits in improving inflammatory markers such as CRP, lymphocytes, D-dimer, or oxygen saturation levels over standard drug therapy, according to meta-analysis data.

Forecasting COVID-19 recovered cases with Artificial Neural Networks to enable designing an effective blood supply chain

This study introduces a forecasting model to help design an effective blood supply chain mechanism for tackling the COVID-19 pandemic. In doing so, first, the number of people recovered from COVID-19 is forecasted using the Artificial Neural Networks (ANNs) to determine potential donors for convalescent (immune) plasma (CIP) treatment of COVID-19. This is performed explicitly to show the applicability of ANNs in forecasting the daily number of patients recovered from COVID-19. Second, the ANNs-based approach is further applied to the data from Italy to confirm its robustness in other geographical contexts. Finally, to evaluate its forecasting accuracy, the proposed Multi-Layer Perceptron (MLP) approach is compared with other traditional models, including Autoregressive Integrated Moving Average (ARIMA), Long Short-term Memory (LSTM), and Nonlinear Autoregressive Network with Exogenous Inputs (NARX). Compared to the ARIMA, LSTM, and NARX, the MLP-based model is found to perform better in forecasting the number of people recovered from COVID-19. Overall, the findings suggest that the proposed model is robust and can be widely applied in other parts of the world in forecasting the patients recovered from COVID-19.

Convalescent plasma treatment for patients of 80 years and older with COVID-19 pneumonia

BackgroundOlder patients, frequently with multiple comorbidities, have a high mortality from COVID-19 infection. Convalescent plasma (CP) is a therapeutic option for these patients. Our objective is to retrospectively evaluate the efficacy and adverse events of CP treatment in this population group.MethodsForty one patients over 80 years old with COVID-19 pneumonia received CP added to standard treatment, 51.2% with high anti-SARS-CoV-2 IgG titers and 48.8% with low titers. Median time between the onset of symptoms and the infusion of plasma was 7 days (IQR 4–10). A similar group of 82 patients who received only standard treatment, during a period in which CP was not available, were selected as a control group.ResultsIn-hospital mortality was 26.8% for controls and 14.6% for CP patients (P = 0.131) and ICU admission was 8.5% for controls and 4.9% for CP patients (P = 0.467). Mortality tended to be lower in the high-titer group (9.5%) than in the low-titer group (20%), and in patients transfused within the first 7 days of symptom onset (10%) than in patients transfused later (19.1%), although the differences were not statistically significant (P = 0.307 and P = 0.355 respectively). There was no difference in the length of hospitalization. No significant adverse events were associated with CP treatment.ConclusionsConvalescent plasma treatment in patients over 80 years old with COVID-19 pneumonia was well tolerated but did not present a statistically significant difference in hospital mortality, ICU admission, or length of hospitalization. The results should be interpreted with caution as only half the patients received high-titer CP and the small number of patients included in the study limits the statistical power to detect significant differences.Trial registrationCEIm Cantabria # 2020.127.

Mortality Reduction in ICU-Admitted COVID-19 Patients in Suriname after Treatment with Convalescent Plasma Acquired Via Gravity Filtration

Introduction: Although convalescent plasma (CP) treatment is a potential therapeutic option for patients with COVID-19, there is a paucity of data from intensive care unit (ICU) patients with COVID-19 in low-resource settings, such as Suriname. CP was produced by a novel gravity-based filtration method. Methods: In an open-label, multi-center, non-randomized prospective clinical trial, patients with severe or life- threatening COVID-19 symptoms (n=28) with CP treatment were compared with standard treatment alone (n=50). A pre-planned interim analysis is reported. The primary endpoint was a 28-day ICU mortality. Secondary endpoints were changes two days after treatment initiation in pulmonary oxygen exchange capacity (PF ratio) and chest x-ray (CXR) score. Results: Mortality occurred in 18% (CP: 5/28) vs. 36% (Control:18/50). CP treatment of severe COVID-19 resulted in a higher probability of survival, with a hazard ratio (HR) of 0.22 (95% CI, 0.074-0.067), correcting for age, the presence of diabetes and COVID-19 severity. In the severe group, CP resulted in an improved CXR score (P = 0.0013) and increase in PF ratio (P = 0.011) as compared to standard therapy. The gravity-based plasmapheresis method used for CP production was well-tolerated and no adverse events were observed in the donors. Discussion: CP therapy in combination with standard treatment resulted in 78% reduction of 28-day ICU mortality (HR = 0.22) compared to standard treatment alone. Both CXR-score and PF ratio changes represent effective indicators for the treatment effect of CP after two days. The novel CP production method was effective and represents a practical solution for Low- and middle-income countries to produce CP.

Results of the CAPSID randomized trial for high-dose convalescent plasma in patients with severe COVID-19.

BACKGROUNDCOVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.METHODSPatients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21.ResultsThe primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group.ConclusionCCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies.Trial registrationClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802.

Convalescent Plasma Therapy for COVID-19 is a Challenging Option Review

The guiding principle of plasma therapy can be utilized for prophylaxis and treatment reasons, taking into account non-availability of suitable vaccination for prevention or no settled conclusive cure for SARS-CoV-2, plasma therapy is obtaining importance in a current pandemic as one of the treatment options of COVID-19. Despite the fact that, it has been said to be a useful approach in exceptional preliminary studies, convalescent plasma (CP) treatment has various limitations. In this review, an attempt has been made to audit positive viewpoints, negative views and specific limitations of the CP therapy for COVID-19 cases. The outcomes of various studies show that CP treatment would possibly be considered one of the alternatives but while questioning about it as a therapeutic approach, thinking about beneficial aspects, the negative aspects and barriers are to be considered before its administration as a therapeutic agent.

The Effectiveness of Convalescent Plasma for the Treatment of Novel Corona Virus Disease 2019: A Systematic Review and Meta-Analysis

Background: Coronavirus disease 2019 (COVID-19), sweeping across the world, has created a worldwide pandemic. Effective treatments of COVID-19 are extremely urgent.Objective: To analyze the efficacy and safety of convalescent plasma (CCP) on patients with COVID-19.Methods: All the relevant studies were searched from PubMed, EMBASE,Cochrane library, Scopus, Web of Science, CBM, CNKI, Wan fang, VIP, Medrxiv, Biorxiv, and SSRN on July 19, 2021. PICOS criteria were as follows: (P) the study interests were human subjects with the infection of COVID-19; (I) the intervention of interest was CCP; (C) comparator treatments contained placebo, sham therapy, and standard treatment; (O) the primary outcome was mortality rates by the novel coronavirus. The secondary outcomes included the incidence of serious adverse events, the rate of ICU admission and mechanical ventilation (MV); the length of hospital stay; the duration of MV and ICU stay; the antibody levels, inflammatory factor levels, and viral loads. (S) Only randomized controlled trials (RCTs) of CCP were included. Subanalysis, quality assessment, sensitive analysis, and publication bias were conducted by two reviewers independently.Results: Sixteen RCTs were included and enrolled a total of 16,296 participants in this meta-analysis. The pooled data showed that no significant difference was observed in reducing the rate of overall mortality between CCP treatment group and placebo group (OR 0.96; 95% CI 0.90 to 1.03; p = 0.30; I2 = 6%). According to the results of subgroup analysis, severe or critical patients with CCP showed significant difference in reducing the 28-day mortality of compared with placebo (OR 0.58, 95% CI 0.36 to 0.93, p = 0.02, I2 = 0%). CCP groups have a significantly shorter duration of MV compared with the control group (weighted MD −1.00, 95% CI −1.86 to −0.14 d p = 0.02, I2 = 0%). No significant difference was observed in the length of hospital stay, the duration of ICU, and the rate of ICU and MV. There is no conclusive evidence about the safety of CCP.Conclusion: Convalescent plasma can significantly reduce the 28-day mortality of severe or critical COVID-19 patients and the duration of MV. However, more evidence was needed to prove the safety of convalescent plasma.