Background and Objectives In the absence of a vaccine or specific antiviral drugs against SARS-CoV-2 COVID-19 convalescent plasma became one of the experimental treatment options in many countries. Aim of this study was to assess the impact of different pathogen reduction technologies on the immunological properties of COVID-19 convalescent plasma. Materials and Methods In our experiment 140 doses of plasma collected by plasmapheresis from COVID-19 convalescent donors were subjected to pathogen reduction with one of three different methods: methylene blue (M), riboflavin (R), and amotosalen (A). To conduct a paired two-sample comparison each plasma dose was divided into 2 that were treated by one of these technologies. The titres of SARS-CoV2 neutralizing antibodies (NtAbs) and levels of specific immunoglobulins to RBD, S- and N- proteins of SARS-CoV-2 were measured before and after pathogen reduction. Results All methods reduced NtAbs titers significantly but not at the same grade: among units with the initial titre 80 or above, 81% of units had unchanged titres while 19% decreased by 1 step after methylene blue; 60% unchanged and 40% - decreased by 1 step after amotosalen; 43% unchanged, 67% a one-step decrease and 6% - a two-step decrease after riboflavin. Pairwise two-sample comparisons (M vs A, M vs R and A vs R) revealed the most prominent and statistically significant decrease in all studied parameters (except anti-RBD) following pathogen reduction with riboflavin. Conclusion Pathogen reduction with amotosalen and methylene blue provides the greater likelihood of preserving the immunological properties of the COVID-19 convalescent plasma compared to riboflavin.
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.
АКТУАЛЬНОСТЬ. Темпы развития пандемии новой коронавирусной инфекции COronaVIrus Disease 2019 (COVID-19) и высокая летальность обусловили необходимость поиска всех возможных методов лечения. Реконвалесцентная плазма (РП) стала ценным эмпирическим ресурсом для поддержки здравоохранения, особенно на начальном этапе пандемии COVID-19. Она по-прежнему остается объектом внимания многих ученых, в то время как данные относительно эффективности РП являются достаточно противоречивыми. ЦЕЛЬ ИССЛЕДОВАНИЯ. Целью настоящего обзора является анализ результатов современных исследований по эффективности и безопасности клинического применения РП. МАТЕРИАЛЫ И МЕТОДЫ. Обзор литературы был проведен в электронных базах данных PubMed, MedRxiv, Cochrane Library, Cochrane COVID-19 study registry с 7 июня 2021 г. по 20 декабря 2021 г. РЕЗУЛЬТАТЫ. В данной работе выполнен обзор основных сравнительных ретроспективных или проспективных исследований по применению РП. Применение РП известно с 1880-х гг. при лечении дифтерии, испанского гриппа, кори, полиомиелита, а в XXI в. РП использовали при эпидемии лихорадки Эбола, вируса гриппа H1N1, других коронавирусах. Терапия РП основана на концепции пассивной иммунизации и включает в себя введение антител от доноров-реконвалесцентов, обладающих вирус-нейтрализующей активностью (ВНА) к данному вирусу. В целях минимизации рисков гемотрансмиссивных инфекций используются технологии редукции патогенов. Исторические и текущие данные об использовании РП подтверждают безопасность ее использования. Были рассмотрены критерии эффективности применения и сроки назначения РП. Представлены клинические данные, подтверждающие эффективность РП у определенных групп пациентов. ВЫВОДЫ. Применение РП является безопасным и целесообразно у серонегативных больных с COVID-19 на ранних сроках заболевания или при наличии иммунодефицитного состояния. Наибольшей эффективностью обладает РП с высокими титрами ВНА. У тяжелых больных на поздних сроках болезни терапия РП не приводит к регрессии заболевания и увеличению выживаемости.
Results: Serum OPG concentrations increased throughout the study period (p = 7.26x10 -5 ) while RANKL concentrations did not change (p = 0.19). The OPG:RANKL ratio exhibited a 6.2-fold increase between Days 1 and 5. CTX-1 concentrations were lower (p = 0.006) 30 minutes after the 50 U/kg FVIII infusion. CTX-1 response for each participant was assessed using linear regression throughout the time course. Spine L1-L4 Z-score (SZ) and Hip Total Z-score (HTZ) correlate with CTX-1 response (p = 3.4x10 -4 and 0.014, respectively). The mean age of participants was 25.2 ± 2.1 at time of first study visit. Participants had a mean SZ of −0.74 ± 0.34, HTZ of −0.17 ± 0.32, Hip Neck Z-score (HNZ) of −0.16 ± 0.35, and HJHS of 20 ± 5. HTZ and HNZ decreased significantly with patient age (p = 0.027 and 0.032) while SZ and HJHS did not (p = 0.18 and 0.16). Consequently, age correction was applied to BMD comparisons. Statistical comparisons between HAL, EQ-5D-3L, and BHQ answers, BMD data, and HJHS are shown in Table 1. Summary/Conclusion: This prospective study demonstrates a relationship between FVIII deficiency and bone disease in PwH. OPG acts as a decoy ligand to RANKL, inhibiting osteoclastic bone resorption. The observed increase in OPG:RANKL ratio suggests FVIII has a direct impact on this pathway. Decreased CTX-1 concentrations following factor infusion and correlations between CTX-1 response and BMD further suggests that FVIII plays a role in moderating bone remodeling. Hemophilia-associated bone and joint pathology is associated with decreased quality of life. Correlations between BMD and questionnaire responses demonstrate that poor bone and joint health is physically limiting, causes discomfort, and negatively impacts perceptions of personal well-being. Furthermore, correlations between BMD and HJHS and ISTH-BAT responses (Table 1) illustrate a relationship between bleeding management and skeletal health. PwH with lower BMD report more nose and gum bleeds, suggesting a link between FVIII replacement and skeletal health. Bleeds in the extremities were not correlated with decreased BMD or increased HJHS, but abdominal (stomach, iliopsoas) and other bleeds were. Analysis of these data is ongoing.
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