Effect of time and titer in convalescent plasma therapy for COVID-19

Candia, Paola de; Prattichizzo, Francesco; Garavelli, S.; Grotta, Rosalba La; Rosa, Annunziata De; Pontarelli, Agostina; Parrella, Roberto; Ceriello, Antonio; Matarese, Giuseppe

doi:10.1016/j.isci.2021.102898

Cited by 17 publications

(17 citation statements)

References 85 publications

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“…Several studies suggest that the effect of CCP is dependent on its antibody titers [ 10 , 18 ], hence the importance of proper donor selection. The concentration of antibodies is known to increase during the first week of symptoms [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

“…In particular, the CONCOR-1 study, an international randomized controlled trial, aimed to assess the efficacy of this therapy using mortality and intubation of patients at day 30 as the primary endpoint [ 10 ]. The trial, and others as reviewed elsewhere [ 18 ], selected the CCP based on the titer of anti-SARS-CoV-2 antibodies to ultimately transfuse it to infected patients [ 10 ]. Ultimately, this study failed to show the superiority of CCP over standard of care and even raised the possibility of harmful effects in plasma with low antibody content [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells

et al. 2022

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Convalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between the immune response and the resolution of inflammation from peripheral tissues, including the artery wall. As vascular complications are a key pathogenic mechanism in COVID-19, leading to inflammation and multiple organ failure, we believe that sustaining lymphatic vessel function should be considered to define optimal CPT. We herein sought to determine what specific COVID-19 convalescent plasma (CCP) characteristics should be considered to limit inflammation-driven lymphatic endothelial cells (LEC) dysfunction. CCP donated 16 to 100 days after the last day of symptoms was characterized and incubated on inflammation-elicited adult human dermal LEC (aHDLEC). Plasma analysis revealed that late donation correlates with higher concentration of circulating pro-inflammatory cytokines. Conversely, extracellular vesicles (EVs) derived from LEC are more abundant in early donated plasma (r = −0.413, p = 0.004). Thus, secretion of LEC-EVs by an impaired endothelium could be an alarm signal that instigate the self-defense of peripheral lymphatic vessels against an excessive inflammation. Indeed, in vitro experiments suggest that CCP obtained rapidly following the onset of symptoms does not damage the aHDLEC junctions as much as late-donated plasma. We identified a particular signature of CCP that would counteract the effects of an excessive inflammation on the lymphatic endothelium. Accordingly, an easy and efficient selection of convalescent plasma based on time of donation would be essential to promote the preservation of the lymphatic and immune system of infected patients.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells

et al. 2022

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“…The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram is reported in Figure 1 . After the full texts were scrutinized against the inclusion and exclusion criteria, 29 SRs were included in the umbrella review [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ] and 23 SRs were excluded [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , …”

Section: Resultsmentioning

confidence: 99%

“…Of the 29 SRs included in the overview, 26 were focused exclusively on COVID-19 [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], while three were focused on respiratory pandemics and on beta coronaviruses infections [ 10 , 19 , 30 ]. Two SRs [ 17 , 22 ] were a subgroup analysis of other reviews [ 16 , 21 ].…”

Section: Resultsmentioning

confidence: 99%

Safety and Efficacy of Convalescent Plasma in COVID-19: An Overview of Systematic Reviews

Franchini

Corsini²,

Focosi³

et al. 2021

Diagnostics

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Convalescent plasma (CP) from patients recovered from COVID-19 is one of the most studied anti-viral therapies against SARS-COV-2 infection. The aim of this study is to summarize the evidence from the available systematic reviews on the efficacy and safety of CP in COVID-19 through an overview of the published systematic reviews (SRs). A systematic literature search was conducted up to August 2021 in Embase, PubMed, Web of Science, Cochrane and Medrxiv databases to identify systematic reviews focusing on CP use in COVID-19. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. The following outcomes were analyzed: mortality, viral clearance, clinical improvement, length of hospital stay, adverse reactions. In addition, where possible, subgroup analyses were performed according to study design (e.g., RCTs vs. non-RCTs), CP neutralizing antibody titer and timing of administration, and disease severity. The methodological quality of included studies was assessed using the checklist for systematic reviews AMSTAR-2 and the GRADE assessment. Overall, 29 SRs met the inclusion criteria based on 53 unique primary studies (17 RCT and 36 non-RCT). Limitations to the methodological quality of reviews most commonly related to absence of a protocol (11/29) and funding sources of primary studies (27/29). Of the 89 analyses on which GRADE judgements were made, effect estimates were judged to be of high/moderate certainty in four analyses, moderate in 38, low in 38, very low in nine. Despite the variability in the certainty of the evidence, mostly related to the risk of bias and inconsistency, the results of this umbrella review highlight a mortality reduction in CP over standard therapy when administered early and at high titer, without increased adverse reactions.

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“…74). The mortality of COVID-19 patients was significantly reduced when convalescent plasma was provided in the early stages of the disease, and the use of plasma with high antibody titers did not increase the risk of death compared with unselected plasma (Refs 75,76). The use of convalescent plasma not only transiently increased the level of systemic anti-SARS-CoV antibodies but also promoted the specific T-cell response (Ref.…”

Section: Antibody-based Therapiesmentioning

confidence: 99%

The immunology and immunotherapy for COVID-19

Liu

Zhou

et al. 2021

Expert Rev. Mol. Med.

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The ongoing global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and significantly impacts the world economy and daily life. Symptoms of COVID-19 range from asymptomatic to fever, dyspnoea, acute respiratory distress and multiple organ failure. Critical cases often occur in the elderly and patients with pre-existing conditions. By binding to the angiotensin-converting enzyme 2 receptor, SARS-CoV-2 can enter and replicate in the host cell, exerting a cytotoxic effect and causing local and systemic inflammation. Currently, there is no specific treatment for COVID-19, and immunotherapy has consistently attracted attention because of its essential role in boosting host immunity to the virus and reducing overwhelming inflammation. In this review, we summarise the immunopathogenic features of COVID-19 and highlight recent advances in immunotherapy to illuminate ideas for the development of new potential therapies.

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Effect of time and titer in convalescent plasma therapy for COVID-19

Cited by 17 publications

References 85 publications

Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells

Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells

Safety and Efficacy of Convalescent Plasma in COVID-19: An Overview of Systematic Reviews

The immunology and immunotherapy for COVID-19

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