Clinical predictors of donor antibody titer and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial

Madariaga, Maria Lucia; Guthmiller, Jenna J.; Schrantz, Stephen; Jansen, Maud O.; Christensen, Chancey; Kumar, Madan; Prochaska, Micah T.; Wool, Geoffrey D.; Durkin‐Celauro, Amy; Oh, Won H.; Trockman, Laura; Vigneswaran, Janani; Keskey, Robert; Shaw, Dustin G.; Dugan, Haley L.; Zheng, Na; Cobb, Mari; Utset, Henry A.; Wang, Jiaolong; Stovicek, Olivia; Bethel, Cindy; Matushek, Scott; Giurcanu, Mihai; Beavis, Kathleen G.; Sabato, Diego di; Meltzer, David; Ferguson, Mark K.; Kress, John P.; Shanmugarajah, Kumaran; Matthews, Jeffrey B.; Fung, John; Wilson, Patrick C.; Alverdy, John C.; Donington, Jessica S.

doi:10.1101/2020.06.21.20132944

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…The intermediate approach, whenever allowed by privacy regulations, is making calls to positive cases under home-based quarantine to solicit donations; given the large numbers of such cases, some of them are likely to be regular donors, and home-based convalescence suggests that they are fit enough to donate. Nevertheless, lessons from MERS ( 17 ) and preliminary evidence with COVID-19 ( 18 – 20 ) suggest that patients with mild symptoms may develop low-titer antibodies, making antibody titration even more important in the population-wide and home-based approaches. Plasma samples collected an average of 30 days after the onset of symptoms had undetectable half-maximal neutralizing titers in 18% of donors ( 21 ).…”

Section: Cp Donor Recruitment Strategiesmentioning

confidence: 99%

Convalescent Plasma Therapy for COVID-19: State of the Art

Focosi¹,

et al. 2020

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SUMMARY Convalescent plasma (CP) therapy has been used since the early 1900s to treat emerging infectious diseases; its efficacy was later associated with the evidence that polyclonal neutralizing antibodies can reduce the duration of viremia. Recent large outbreaks of viral diseases for which effective antivirals or vaccines are still lacking has renewed the interest in CP as a life-saving treatment. The ongoing COVID-19 pandemic has led to the scaling up of CP therapy to unprecedented levels. Compared with historical usage, pathogen reduction technologies have now added an extra layer of safety to the use of CP, and new manufacturing approaches are being explored. This review summarizes historical settings of application, with a focus on betacoronaviruses, and surveys current approaches for donor selection and CP collection, pooling technologies, pathogen inactivation systems, and banking of CP. We additionally list the ongoing registered clinical trials for CP throughout the world and discuss the trial results published thus far.

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Section: Cp Donor Recruitment Strategiesmentioning

confidence: 99%

Convalescent Plasma Therapy for COVID-19: State of the Art

Focosi¹,

et al. 2020

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“…Two study reported that asymptomatic healthcare workers did develop antibodies. 161,162 • Fever appears to have a consistent relationship with seropositivity and antibody titres, 29,158,160 although other symptoms such as ageusia have also been associated. 156,158…”

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confidence: 97%

“…Three studies report an association between COVID-19 symptoms and seropositivity, [156][157][158] and with higher titres of IgG, 29,159 IgA, 159 and anti-RBD and anti-S antibodies. 160…”

mentioning

confidence: 99%

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Antibody response to SARS-CoV-2 infection in humans: a systematic review

Post

Eddy

Huntley

et al. 2020

Preprint

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Introduction Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (75%) were observational in design, and included papers were generally of moderate quality based on hospitalised patients. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, and up to around 3 months from disease onset, although inconsistencies remain concerning clinical correlates. Development of neutralising antibodies following SARS-CoV-2 infection is typical, although titres may be low. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross reactivity but limited cross neutralisation occurs with other HCoVs. Evidence for protective immunity in vivo is limited to small, short-term animal studies, which show promising initial results in the immediate recovery phase. Interpretation Published literature on immune responses to SARS-CoV-2 is of variable quality with considerable heterogeneity with regard to methods, study participants, outcomes measured and assays used. Antibody dynamics have been evaluated thoroughly in the acute phase but longer follow up and a comprehensive assessment of the role of demographic characteristics and disease severity is needed. The role of protective neutralising antibodies is emerging, with implications for therapeutics and vaccines. Large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

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“…What other evidence underpinned the FDA’s controversial decision? The most recent version of the Cochrane living systematic review on convalescent plasma9 was available, along with more recent randomised and non-randomised studies 4101112131415. However, the only two randomised trials (189 participants in total)34 could not be combined in meta-analyses because they used different times for assessing mortality and different rating scales for clinical outcomes.…”

mentioning

confidence: 99%