Biologic correlates of beneficial convalescent plasma therapy in a COVID-19 patient reveal disease resolution mechanisms

Bruiners, Natalie; Guerrini, Valentina; Ukey, Rahul; Dikdan, Ryan; Yang, Jason H.; Mishra, Pankaj Kumar; Onyuka, Alberta; Handler, Deborah; Vieth, Joshua A.; Carayannopulos, Mary; Guo, Shuang; Pollen, Maressa; Pinter, Abraham; Tyagi, Sanjay; Feingold, Daniel L.; Philipp, Claire S.; Libutti, Steven K.; Gennaro, Maria Laura

doi:10.1101/2022.02.03.22269612

Cited by 3 publications

(2 citation statements)

References 75 publications

(79 reference statements)

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“…For these exploratory analyses, 13 uncontrolled large case series without individual patient data enrolling 358 participants were included in descriptive analysis . In this study, 125 case reports or case series enrolling 265 participants were included for patient-level exploratory analyses. One study was included in both the descriptive analysis and the individual patient data analysis because individual patient data were available only for a subgroup of patients.…”

Section: Resultsmentioning

confidence: 99%

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis

et al. 2023

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ImportancePatients who are immunocompromised have increased risk for morbidity and mortality associated with coronavirus disease 2019 (COVID-19) because they less frequently mount antibody responses to vaccines. Although neutralizing anti-spike monoclonal-antibody treatment has been widely used to treat COVID-19, evolutions of SARS-CoV-2 have been associated with monoclonal antibody-resistant SARS-CoV-2 variants and greater virulence and transmissibility of SARS-CoV-2. Thus, the therapeutic use of COVID-19 convalescent plasma has increased on the presumption that such plasma contains potentially therapeutic antibodies to SARS-CoV-2 that can be passively transferred to the plasma recipient.ObjectiveTo assess the growing number of reports of clinical experiences of patients with COVID-19 who are immunocompromised and treated with specific neutralizing antibodies via COVID-19 convalescent plasma transfusion.Data SourcesOn August 12, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma use in patients who are immunocompromised.Study SelectionRandomized clinical trials, matched cohort studies, and case report or series on COVID-19 convalescent plasma use in patients who are immunocompromised were included. The electronic search yielded 462 unique records, of which 199 were considered for full-text screening.Data Extraction and SynthesisThe study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 3 independent reviewers in duplicate and pooled.Main Outcomes and MeauresThe prespecified end point was all-cause mortality after COVID-19 convalescent plasma transfusion; exploratory subgroup analyses were performed based on putative factors associated with the potential mortality benefit of convalescent plasma.ResultsThis systematic review and meta-analysis included 3 randomized clinical trials enrolling 1487 participants and 5 controlled studies. Additionally, 125 case series or reports enrolling 265 participants and 13 uncontrolled large case series enrolling 358 participants were included. Separate meta-analyses, using models both stratified and pooled by study type (ie, randomized clinical trials and matched cohort studies), demonstrated that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for the amalgam of both randomized clinical trials and matched cohort studies (risk ratio [RR], 0.63 [95% CI, 0.50-0.79]).Conclusions and RelevanceThese findings suggest that transfusion of COVID-19 convalescent plasma is associated with mortality benefit for patients who are immunocompromised and have COVID-19.

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Section: Resultsmentioning

confidence: 99%

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis

et al. 2023

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“… Along with the delay of CP administration day, the length of stay in the ICU grew. Natalie Bruiners et al 139 Beneficial CPT in a patient with COVID-19 revealed disease-resolution pathways by its biological correlates (CR) Hydroxychloroquine, methotrexate, rituximab infusion, azithromycin 4-litter supplemental O 2 Day 40: 400 mL of COVID-19 CCP from an unidentifiable donor The patient was given 600 mL of her relative’s CP on day 54. On day 54, the patient’s O 2 saturation increased to the point where supplemental O 2 was no longer needed.…”

Section: Introductionmentioning

confidence: 99%

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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COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review

Senefeld

Franchini

Mengoli

et al. 2022

Preprint

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Immunosuppressed patients have increased risk for morbidity and mortality from COVID-19 because they less frequently mount antibody responses to vaccines and often cannot tolerate small-molecule antivirals. The Omicron variant of concern of SARS-CoV-2 has progressively defeated anti-Spike mAbs authorized so far, paving the way to a return to COVID-19 convalescent plasma (CCP) therapy. In this systematic review we performed a metanalysis of 6 controlled studies (including 2 randomized controlled trials; totaling 368 treated patients and 1119 control), an individual patient data analysis of 125 case reports/series (totaling 265 patients), and a descriptive analysis of 13 uncontrolled large case series without individual patient data available (totaling 358 patients). The metanalysis showed a risk ratio for mortality of 0.61 in treatment with CCP versus standard of care for immunosuppressed COVID-19 patients. On the basis of this evidence, we encourage initiation of high-titer CCP from vaccinees (hybrid plasma) in immunocompromised patients.

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Biologic correlates of beneficial convalescent plasma therapy in a COVID-19 patient reveal disease resolution mechanisms

Cited by 3 publications

References 75 publications

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis

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

COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review

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