Early administration of <scp>COVID</scp>‐19 convalescent plasma with high titer antibody content by live viral neutralization assay is associated with modest clinical efficacy

Belov, Artur; Huang, Yin; Villa, Carlos H.; Whitaker, Barbee I.; Forshee, Richard A.; Anderson, Steven A.; Eder, Anne F.; Verdun, Nicole; Joyner, Michael J.; Wright, Scott; Carter, Rickey E.; Hung, Deborah T.; Homer, Mary J; Hoffman, Corey M.; Lauer, Michael S.; Marks, Peter

doi:10.1002/ajh.26531

Cited by 15 publications

(8 citation statements)

References 80 publications

(141 reference statements)

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“… 100–103 As per the given limitations of available data as on August 2020 and the extent of outbreak and CCP usage under the expanded access protocol was escalated, and initial statistics on the potential efficacy of CCP were necessary to support the regulatory decision-making process. 104 …”

Section: Discussionmentioning

confidence: 99%

“…The case findings are as follows: the strengths of the analysis on early administration of CCP with high titer antibody content by live viral neutralization assay are associated with modest clinical efficacy, providing greater precision concerning CCP biologic activity and the power to detect modest treatment effects in the overall heterogeneous hospitalized population, reflecting real-world use of CCP in the early pandemic. 104 …”

Section: Discussionmentioning

confidence: 99%

“… This outstanding case adds weight to the expanding body of evidence demonstrating that, when HT dosages are given, CP is successful in curing ICPs. Artur Belov et al 104 Clinical utility is moderate based on the earlier infusion of COVID-19 CP with a high AbsT concentration as determined by a live viral neutralized assay (ORA) 23,118 total patients Received 1 unit of CP were separated into 2 groups those who received HTCP (>250 50%, ID 50; n = 13,636) and those receiving LTCP (≤250 ID 50; n = 9482). HTCP transfusions led to absolute improvements in average 7 and 28-day DR of 1.1% and 1.7%, respectively, when compared to non-intubated patients who administered LTCP.…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness of COVID-19 Convalescent Plasma (CCP) During the Pandemic Era: A Literature Review

Kandula¹,

Tuji²,

Gudeta³

et al. 2023

JBM

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Worldwide pandemic with coronavirus disease-2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As November 2, 2022, World Health Organization (WHO) received 628,035,553 reported incidents on COVID-19, with 6,572,800 mortalities and, with a total 12,850,970,971 vaccine doses have been delivered as of October 31, 2022. The infection can cause mild or self-limiting symptoms of pulmonary and severe infections or death may be caused by SARS-CoV-2 infection. Simultaneously, antivirals, corticosteroids, immunological treatments, antibiotics, and anticoagulants have been proposed as potential medicines to cure COVID-19 affected patients. Among these initial treatments, COVID-19 convalescent plasma (CCP), which was retrieved from COVID-19 recovered patients to be used as passive immune therapy, in which antibodies from cured patients were given to infected patients to prevent illness. Such treatment has yielded the best results in earlier with preventative or early stages of illness. Convalescent plasma (CP) is the first treatment available when infectious disease initially appears, although few randomized controlled trials (RCTs) were conducted to evaluate its effectiveness. The historical record suggests with potential benefit for other respiratory infections, as coronaviruses like Severe Acute Respiratory Syndrome-CoV-I (SARS-CoV-I) and Middle Eastern Respiratory Syndrome (MERS), though the analysis of such research is constrained by some non-randomized experiments (NREs). Rigorous studies on CP are made more demanding by the following with the immediacy of the epidemics, CP use may restrict the ability to utilize it for clinical testing, non-homogenous nature of product, highly decentralized manufacturing process; constraints with capacity to measure biologic function, ultimate availability of substitute therapies, as antivirals, purified immune globulins, or monoclonal antibodies. Though, it is still not clear how effectively CCP works among hospitalized COVID-19 patients. The current review tries to focus on its efficiency and usage in clinical scenarios and identifying existing benefits of implementation during pandemic or how it may assist with future pandemic preventions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effectiveness of COVID-19 Convalescent Plasma (CCP) During the Pandemic Era: A Literature Review

Kandula¹,

Tuji²,

Gudeta³

et al. 2023

JBM

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“…Several RCTs of CCP for treatment of moderate-to-severe hospitalized COVID-19 patients, typically at 7 or more days post-symptom-onset, did not find clinical benefits [ 8 , 9 , 16 – 22 ], although some trials found signals of clinical benefit, sometimes in certain subgroups [ 21 , 23 – 26 ]. Assessment of patients treated under the EAP found a modest survival benefit in patients who received high-titer CCP compared to those who received low-titer CCP [ 27 , 28 ]. A Bayesian reanalysis of RECOVERY argued that it remained plausible that CCP has a small but clinically significant effect on mortality in seronegative patients [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Multi-center matched cohort study of convalescent plasma for hospitalized patients with COVID-19

et al. 2022

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Background Although frequently used in the early pandemic, data on the effectiveness of COVID-19 convalescent plasma (CCP) remain mixed. We investigated the effectiveness and safety of CCP in hospitalized COVID-19 patients in real-world practices during the first two waves of the pandemic in a multi-hospital healthcare system in Texas. Methods and findings Among 11,322 hospitalized patients with confirmed COVID-19 infection from July 1, 2020 to April 15, 2021, we included patients who received CCP and matched them with those who did not receive CCP within ±2 days of the transfusion date across sites within strata of sex, age groups, days and use of dexamethasone from hospital admission to the match date, and oxygen requirements 4–12 hours prior to the match date. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effectiveness outcomes in a propensity score 1:1 matched cohort. Pre-defined safety outcomes were described. We included 1,245 patients each in the CCP treated and untreated groups. Oxygen support was required by 93% of patients at the baseline. The pre-defined primary effectiveness outcome of 28-day in-hospital all-cause mortality (HR = 0.85; 95%CI: 0.66,1.10) were similar between treatment groups. Sensitivity and stratified analyses found similar null results. CCP-treated patients were less likely to be discharged alive (HR = 0.82; 95%CI: 0.74, 0.91), and more likely to receive mechanical ventilation (HR = 1.48; 95%CI: 1.12, 1.96). Safety outcomes were rare and similar between treatment groups. Conclusion The findings in this large, matched cohort of patients hospitalized with COVID-19 and mostly requiring oxygen support at the time of treatment, do not support a clinical benefit in 28-day in-hospital all-cause mortality for CCP. Future studies should assess the potential benefits with specifically high-titer units in perhaps certain subgroups of patients (e.g. those with early disease or immunocompromised).

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“…In this framework, three matched cohort studies 98,109,114 enrolling 330 participants and 12 case series 54,[134][135][136][137][138][139][140][141][142][143][144] enrolling 29,361 participants were included in this subgroup analysis. In this subgroup meta-analysis, treatment with COVID-19 convalescent plasma containing high antibody levels was associated with a 15% decrease in mortality rates compared to convalescent plasma containing low antibody levels, with a pooled risk ratio estimate of 0.85 (95% CI, 0.73 to 0.99).…”

Section: Subgroup Analysesmentioning

confidence: 99%

Mortality rates among hospitalized patients with COVID-19 treated with convalescent plasma A Systematic review and meta-analysis

Senefeld

Gorman

Johnson

et al. 2023

Preprint

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IMPORTANCE. Many hospitalized patients with COVID-19 have been treated with convalescent plasma. However, it is uncertain whether this therapy lowers mortality and if so, if the mortality benefit is larger among specific subgroups, such as recipients of plasma with high antibody content and patients treated early in the disease course. OBJECTIVE. To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. DATA SOURCES. On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature. STUDY SELECTION. 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 3,841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of five reviewers. DATA EXTRACTION AND SYNTHESIS. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using inverse-variance random-effects model. MAIN OUTCOMES AND MEASURES. 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 demonstrated that transfusion of COVID-19 convalescent plasma was associated with a significant 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, 0.77 [95% CI, 0.64-0.94]). Meta-analysis of subgroups revealed two important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared to 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 significant decrease in mortality compared with the later treatment cohort (OR, 0.63 [95% CI, 0.48 to 0.82]). CONCLUSIONS AND RELEVANCE. COVID-19 convalescent plasma use was associated with a 13% reduced risk in 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.

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Early administration of COVID‐19 convalescent plasma with high titer antibody content by live viral neutralization assay is associated with modest clinical efficacy

Cited by 15 publications

References 80 publications

Effectiveness of COVID-19 Convalescent Plasma (CCP) During the Pandemic Era: A Literature Review

Effectiveness of COVID-19 Convalescent Plasma (CCP) During the Pandemic Era: A Literature Review

Multi-center matched cohort study of convalescent plasma for hospitalized patients with COVID-19

Mortality rates among hospitalized patients with COVID-19 treated with convalescent plasma A Systematic review and meta-analysis

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