Impact of pathogen reduction methods on immunological properties of the COVID‐19 convalescent plasma

Kostin, Alexander I.; Lundgren, Maria; Bulanov, A. Yu.; Ладыгина, Е. А.; Chirkova, Karina S.; Gintsburg, Alexander L.; Logunov, Denis Y.; Dolzhikova, Inna V.; Shcheblyakov, Dmitry V.; Боровкова, Н. В.; Годков, М. А.; Баженов, А И; Shustov, Valeriy V.; Богданова, А. С.; Kamalova, Alina R.; Ganchin, Vladimir V.; Dombrovskiy, Eugene A.; Volkov, Stanislav; Drozdova, Nataliya E.; Петриков, С. С.

doi:10.1111/vox.13056

Cited by 14 publications

(10 citation statements)

References 30 publications

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“…Methylene blue is a method of pathogen inactivation for plasma that is widely used in some countries in Europe. A study from Russia showed that some units of plasma lost neutralising activity with methylene blue inactivation, 34 whereas other studies found no difference. 35 , 36 We analysed the neutralising activity of stored donor samples (ie, before methylene blue treatment) compared with the plasma unit (ie, after methylene blue treatment) in a subgroup of plasma units and we found no differences in neutralising antibody titres (median ID50 1:1256 [IQR 1:709–1:2712] vs 1:1287 [1:349–1:3333]; p=0·32).…”

Section: Discussionmentioning

confidence: 99%

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial

Alemany

Millat-Martinez

Corbacho-Monné

et al. 2022

The Lancet Respiratory Medicine

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Section: Discussionmentioning

confidence: 99%

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial

Alemany

Millat-Martinez

Corbacho-Monné

et al. 2022

The Lancet Respiratory Medicine

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“…Prior studies have shown that photoinactivation with methylene blue does not significantly reduce the titers of SARS‐CoV‐2 antibodies. 36 , 37 In fact, the methylene blue method has been reported to be less detrimental to anti‐SARS‐CoV2‐2 titers than other pathogen‐reduction technologies currently applied to donated plasma. 36 However, we cannot certainly disregard some decrease in the in vivo neutralizing capacity due to pathogen‐reduction.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of early transfusion of convalescent plasma with high‐titer SARS‐CoV‐2 neutralizing antibodies in hospitalized patients with COVID‐19

et al. 2022

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Background Despite most controlled trials have shown no measurable benefit of COVID‐19 convalescent plasma (CCP) in patients with COVID‐19, some studies suggest that early administration of CCP with high‐titer anti‐SARS‐CoV‐2 can be beneficial in selected patients. We investigated the efficacy of early administration of high‐titer CCP to patients with COVID‐19 who required hospitalization, Study design and methods Observational, propensity score (PS) matched case–control study of COVID‐19 patients treated with CCP within 72 h of hospital admission and untreated controls from August 2020 to February 2021. All CCP donations had a Euroimmun anti‐SARS‐CoV‐2 sample‐to‐cutoff ratio ≥3. PS matching was based on prognostic factors and presented features with high‐standardized differences between the treated and control groups. The primary endpoint was mortality within 30 days of diagnosis. Results A total of 1604 patients were analyzed, 261 of whom received CCP, most (82%) within 24 h after admission. Median age was 67 years (interquartile range: 56–79), and 953 (60%) were men. Presenting factors independently associated with higher 30‐day mortality were increased age, cardiac disease, hypoxemic respiratory failure, renal failure, and plasma d‐dimer >700 ng/ml. After PS matching, transfusion of CCP was associated with a significant reduction in the 30‐day mortality rate (odds ratio [OR]; 0.94, 95% confidence interval [CI]: 0.91–0.98; p = .001) that extended to the 60th day after COVID‐19 diagnosis (OR: 0.95; 95% CI: 0.92–0.99; p = .01). Conclusion Our results suggest that CCP can still be helpful in selected patients with COVID‐19 and call for further studies before withdrawing CCP from the COVID‐19 therapeutic armamentarium.

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“…Serum samples were collected and the analysis of the neutralizing activity of the convalescent blood plasma was carried out in the microneutralization test described earlier [ 22 ]. Live hCoV-19/Russia/Moscow_PMVL-1/2020 virus variant was employed; test was performed as the microneutralization assay with the Vero E6 cells.…”

Section: Methodsmentioning

confidence: 99%

Fast and Accurate Surrogate Virus Neutralization Test Based on Antibody-Mediated Blocking of the Interaction of ACE2 and SARS-CoV-2 Spike Protein RBD

et al. 2022

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The humoral response to the SARS-CoV-2 S protein determines the development of protective immunity against this infection. The standard neutralizing antibodies detection method is a live virus neutralization test. It can be replaced with an ELISA-based surrogate virus neutralization test (sVNT), measuring the ability of serum antibodies to inhibit complex formation between the receptor-binding domain (RBD) of the S protein and the cellular ACE2 receptor. There are conflicting research data on the sVNT methodology and the reliability of its results. We show that the performance of sVNT dramatically improves when the intact RBD from the Wuhan-Hu-1 virus variant is used as the plate coating reagent, and the HRP-conjugated soluble ACE2 is used as the detection reagent. This design omits the pre-incubation step in separate tubes or separate microplate and allows the simple quantification of the results using the linear regression, utilizing only 3–4 test sample dilutions. When this sVNT was performed for 73 convalescent plasma samples, its results showed a very strong correlation with VNT (Spearman’s Rho 0.83). For the RBD, bearing three amino acid substitutions and corresponding to the SARS-CoV-2 beta variant, the inhibitory strength was diminished for 18 out of 20 randomly chosen serum samples, and the magnitude of this decrease was not similar to the change in overall anti-RBD IgG level. The sVNT assay design with the ACE2-HRP is preferable over the assay with the RBD-HRP reagent and is suitable for mass screening of neutralizing antibodies titers.

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Impact of pathogen reduction methods on immunological properties of the COVID‐19 convalescent plasma

Abstract: Conclusion Pathogen reduction with methylene blue or with amotosalen provides the greater likelihood of preserving the immunological properties of the COVID-19 convalescent plasma compared to riboflavin.

Cited by 14 publications

References 30 publications

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial

Efficacy of early transfusion of convalescent plasma with high‐titer SARS‐CoV‐2 neutralizing antibodies in hospitalized patients with COVID‐19

Fast and Accurate Surrogate Virus Neutralization Test Based on Antibody-Mediated Blocking of the Interaction of ACE2 and SARS-CoV-2 Spike Protein RBD

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