A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia

Bar, Katharine J.; Shaw, Pamela A.; Choi, Grace; Aqui, Nicole A.; Fesnak, Andrew D.; Yang, Jasper B.; Soto‐Calderon, Haideliza; Grajales, Lizette; Starr, Julie; Andronov, Michelle; Mastellone, Miranda; Amonu, Chigozie; Feret, Geoff; DeMarshall, Maureen; Buchanan, Marie; Caturla, Maria; Gordon, James D.; Wanicur, Alan; Monroy, Manuel; Mampe, Felicity; Lindemuth, Emily; Gouma, Sigrid; Mullin, Anne; Barilla, Holly; Pronina, Anastasiya; Irwin, Leah; Thomas, Raeann; Eichinger, Risa A; Demuth, Faye; Prak, Eline T. Luning; Pascual, José L.; Short, William R.; Elovitz, Michal A.; Baron, Jillian T; Meyer, Nuala J.; Degnan, Kathleen; Frank, Ian; Hensley, Scott E.; Siegel, Donald L.; Tebas, Pablo

doi:10.1172/jci155114

Cited by 63 publications

(89 citation statements)

References 48 publications

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“…Thus, we applied system serology to an open-label randomized clinical trial that showed evidence of a mortality benefit from CCP treatment with Receptor-binding domain (RBD) ELISA-selected CCP treatment. (Bar et al, 2021) We found that CCP treatment delayed the evolution of Spike (S)-specific inflammatory antibody responses and induced stronger N-specific antibody responses, both of which were associated with improved outcomes in CCP-treated patients. While pre-existing SARS-CoV-2 specific humoral responses were inversely correlated with response to CCP therapy, participants with the lower antibody function rather than low antibody levels experienced the strongest clinical benefit from CCP.…”

Section: Introductionmentioning

confidence: 78%

“…(Bégin et al, 2021; Herman et al, 2021b; Morgenlander et al, 2021; Natarajan et al, 2021; Wang et al, 2020) To gain a more granular understanding of the CCP properties that contribute to therapeutic efficacy, we profiled the SARS-CoV2-specific antibody response across a group of patients enrolled in a randomized control trial of COVID-19 convalescent plasma (CCP) conducted at University of Pennsylvania. (Bar et al, 2021) The UPenn CCP2 trial enrolled 80 individuals hospitalized with COVID-19 pneumonia (defined as a positive SARS-CoV-2 PCR assay, SaO2 < 93% on room air or supplement oxygen use, and radiologic evidence of pneumonia) as demonstrated in Figure 1A. One participant declined CCP administration and withdrew from the study early, thus we included 79 participants in our analyses; 40 of whom were randomized to receive two units of CCP plus standard of care and 39 received standard of care alone.…”

Section: Resultsmentioning

confidence: 99%

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A role for Nucleocapsid-specific antibody function in Covid-19 Convalescent plasma therapy

Herman

Wang

Burke

et al. 2022

Preprint

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COVID-19 convalescent plasma (CCP), a passive polyclonal antibody therapeutic, has exhibited mixed results in the treatment of COVID-19. Given that the therapeutic effect of CCP may extend beyond the ability of SARS-CoV-2-specific antibody binding and neutralization to influence the evolution of the endogenous antibody response, we took a systematic and comprehensive approach to analyze SARS-CoV-2 functional antibody profiles of participants in a randomized controlled trial of CCP treatment of individuals hospitalized with COVID-19 pneumonia where CCP was associated with both decreased mortality and improved clinical severity. Using systems serology, we found that the clinical benefit of CCP is related to a shift towards reduced inflammatory Spike (S) responses and enhanced Nucleocapsid (N) humoral responses. We found CCP had the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function, rather than S or N antibody levels or participant demographic features. Further, CCP induced immunomodulatory changes to recipient humoral profiles persisted for at least two months, marked by the selective evolution of anti-inflammatory Fc-glycan profiles and persistently expanded nucleocapsid-specific humoral immunity following CCP therapy. Together, our findings identify a novel mechanism of action of CCP, suggest optimal patient characteristics for CCP treatment, identify long-last immunomodulatory effects of CCP, and provide guidance for development of novel N-focused antibody therapeutics for severe COVID-19 hyperinflammation.

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Section: Introductionmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

A role for Nucleocapsid-specific antibody function in Covid-19 Convalescent plasma therapy

Herman

Wang

Burke

et al. 2022

Preprint

Self Cite

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“… 30 whereas, a benefit of early convalescent plasma administration was suggested in patients older than 65 years presenting less than 72 h of symptoms, 31 or in seronegative patients. 32 Other trials with earlier administration of convalescent plasma in the first week of symptoms have also resulted in prevention of disease progression or mortality at 28 days, 33 , 34 suggesting that patients are more likely to be seronegative. Only 29% of our cohort was comprised of patients with undetectable neutralizing antibodies, and there was a higher proportion of seropositive patients in the control group, this could favor plasma groups, and there was still no clinical benefit.…”

Section: Discussionmentioning

confidence: 99%

Treatment of severe COVID-19 patients with either low- or high-volume of convalescent plasma versus standard of care: A multicenter Bayesian randomized open-label clinical trial (COOP-COVID-19-MCTI)

Song

Rocha

Mendrone‐Júnior

et al. 2022

The Lancet Regional Health - Americas

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“…Early transfusion of high titer COVID-19 convalescent plasma (CCP) has emerged as a promising therapy to target SARS-CoV-2 and achieve clinical recovery. 7,8,9 In France, CCP has been proposed in a national monitored access program, notably to hospitalized COVID-19 patients with underlying immunosuppression such as patients with hematological malignancy. While most randomized trials have not reported a benefit of CCP in a general population with COVID-19, 10 we observed that B-cell depleted patients with protracted COVID-19 may benefit from CCP transfusion along with a decrease of all inflammatory parameters, oxygen weaning, and viral clearance.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Convalescent plasma improves overall survival in patients with B-cell lymphoid malignancies and COVID-19: a longitudinal cohort and propensity score analysis

Hueso

Godron

Lanoy

et al. 2022

Preprint

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Patients with hematological malignancies and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatment impair humoral response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears as a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2. We report the effect of CCP in a cohort of 112 patients with hematological malignancies and COVID19 and a propensity score analysis on subgroups of patients with B-cell lymphoid disease treated (n=81) or not (n=120) with CCP between 1 May 2020 and 1 April 2021. The overall survival of the whole cohort was 65% [56-74.9] and 77.5% [68.5-87.7] for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibodies therapy was associated with better overall survival whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20 exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI=31%-80%) in the CCP-treated group compared to the CCP-untreated subgroup, confirmed in the other sensitivity analyses. Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response.

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A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia

Cited by 63 publications

References 48 publications

A role for Nucleocapsid-specific antibody function in Covid-19 Convalescent plasma therapy

A role for Nucleocapsid-specific antibody function in Covid-19 Convalescent plasma therapy

Treatment of severe COVID-19 patients with either low- or high-volume of convalescent plasma versus standard of care: A multicenter Bayesian randomized open-label clinical trial (COOP-COVID-19-MCTI)

Convalescent plasma improves overall survival in patients with B-cell lymphoid malignancies and COVID-19: a longitudinal cohort and propensity score analysis

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