Convalescent Plasma for Preventing Critical Illness in COVID-19: a Phase 2 Trial and Immune Profile

Sturek, Jeffrey M.; Thomas, Tania A; Gorham, James D.; Sheppard, Chelsea A.; Raymond, Allison H; Guex, Kristen Petros de; Harrington, William; Barros, Andrew; Madden, Gregory R; Alkabab, Yosra; Lu, David; Liu, Qin; Poulter, Melinda D.; Mathers, Amy J; Thakur, Archana; Schalk, Dana; Kubicka, Ewa; Lum, Lawrence G.; Heysell, Scott K

doi:10.1128/spectrum.02560-21

Cited by 7 publications

(3 citation statements)

References 33 publications

(33 reference statements)

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“…In contrast, the PennCCP2 trial (US) 44 found a benefit in the primary clinical endpoint of disease severity and 28-day mortality, and a double-blind RCT study by O'Donnell et al, (US and Brazil) 45 found CCP was not associated with significant improvement in day 28 clinical status, but was associated with significantly improved survival. Observational studies [46][47][48][49][50][51][52][53][54] have reported mixed findings, but generally suggest that efficacy is more likely with high titer CCP in earlier and less severe disease, [46][47][48][49][50][51][52][53] or when used in those with impaired immunity. [55][56][57] Interpretation of RCT data, including those in recent metaanalyses, 58,59 is made challenging for multiple reasons: 1) the use of either untitered plasma or plasma qualified by serologic testing alone,…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the PennCCP2 trial (US) 44 found a benefit in the primary clinical endpoint of disease severity and 28‐day mortality, and a double‐blind RCT study by O'Donnell et al, (US and Brazil) 45 found CCP was not associated with significant improvement in day 28 clinical status, but was associated with significantly improved survival. Observational studies 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 have reported mixed findings, but generally suggest that efficacy is more likely with high titer CCP in earlier and less severe disease, 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 or when used in those with impaired immunity. 55 , 56 , 57 …”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2022

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The efficacy of COVID‐19 convalescent plasma (CCP) as a treatment for hospitalized patients with COVID‐19 remains somewhat controversial; however, many studies have not evaluated CCP documented to have high neutralizing antibody titer by a highly accurate assay. To evaluate the correlation of the administration of CCP with titer determined by a live viral neutralization assay with 7‐ and 28‐day death rates during hospitalization, a total of 23 118 patients receiving a single unit of CCP were stratified into two groups: those receiving high titer CCP (>250 50% inhibitory dilution, ID50; n = 13 636) or low titer CCP (≤250 ID50; n = 9482). Multivariable Cox regression was performed to assess risk factors. Non‐intubated patients who were transfused with high titer CCP showed 1.1% and 1.7% absolute reductions in overall 7‐ and 28‐day death rates, respectively, compared to those non‐intubated patients receiving low titer CCP. No benefit of CCP was observed in intubated patients. The relative benefit of high titer CCP was confirmed in multivariable Cox regression. Administration of CCP with high titer antibody content determined by live viral neutralization assay to non‐intubated patients is associated with modest clinical efficacy. Although shown to be only of modest clinical benefit, CCP may play a role in the future should viral variants develop that are not neutralized by other available therapeutics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…Previously, there were studies suggesting the association between receiving CCP and lower 28-day mortality or less progression of diseases ( 67 – 70 ), while recent prospective studies and RCTs indicated that CCP could not lead to elevated antibody titer ( 71 ) or survival benefits in COVID-19 patients ( 72 , 73 ). Our findings supported that COVID-19 patients might not benefit from the transfusion of CCP, which was consistent with the latest WHO and IDSA guideline ( 53 , 54 ).…”

Section: Discussionmentioning

confidence: 99%

The efficiency of convalescent plasma in COVID-19 patients: A systematic review and meta-analysis of randomized controlled clinical trials

et al. 2022

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The objective of this study was to assess whether convalescent plasma therapy could offer survival advantages for patients with novel coronavirus disease 2019 (COVID-19). An electronic search of Pubmed, Web of Science, Embase, Cochrane library and MedRxiv was performed from January 1st, 2020 to April 1st, 2022. We included studies containing patients with COVID-19 and treated with CCP. Data were independently extracted by two reviewers and synthesized with a random-effect analysis model. The primary outcome was 28-d mortality. Secondary outcomes included length of hospital stay, ventilation-free days, 14-d mortality, improvements of symptoms, progression of diseases and requirements of mechanical ventilation. Safety outcomes included the incidence of all adverse events (AEs) and serious adverse events (SAEs). The Cochrane risk-of-bias assessment tool 2.0 was used to assess the potential risk of bias in eligible studies. The heterogeneity of results was assessed by I^2 test and Q statistic test. The possibility of publication bias was assessed by conducting Begg and Egger test. GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used for quality of evidence. This study had been registered on PROSPERO, CRD42021273608. 32 RCTs comprising 21478 patients with Covid-19 were included. Compared to the control group, COVID-19 patients receiving CCP were not associated with significantly reduced 28-d mortality (CCP 20.0% vs control 20.8%; risk ratio 0.94; 95% CI 0.87-1.02; p = 0.16; I² = 8%). For all secondary outcomes, there were no significant differences between CCP group and control group. The incidence of AEs (26.9% vs 19.4%,; risk ratio 1.14; 95% CI 0.99-01.31; p = 0.06; I² = 38%) and SAEs (16.3% vs 13.5%; risk ratio 1.03; 95% CI 0.87-1.20; p = 0.76; I² = 42%) tended to be higher in the CCP group compared to the control group, while the differences did not reach statistical significance. In all, CCP therapy was not related to significantly improved 28-d mortality or symptoms recovery, and should not be viewed as a routine treatment for COVID-19 patients.Trial registration numberCRD42021273608. Registration on February 28, 2022Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, Identifier CRD42022313265.

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Expert consensus on the diagnosis and treatment of severe and critical coronavirus disease 2019 (COVID-19)

Shang

Wu²,

Liu³

et al. 2022

Journal of Intensive Medicine

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Convalescent Plasma for Preventing Critical Illness in COVID-19: a Phase 2 Trial and Immune Profile

Cited by 7 publications

References 33 publications

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

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

The efficiency of convalescent plasma in COVID-19 patients: A systematic review and meta-analysis of randomized controlled clinical trials

Expert consensus on the diagnosis and treatment of severe and critical coronavirus disease 2019 (COVID-19)

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