Characterization of pathogen‐inactivated <scp>COVID</scp>‐19 convalescent plasma and responses in transfused patients

Weisser, Maja; Khanna, Nina; Hedstueck, Anemone; Sutter, Sarah Tschudin; Roesch, Sandra; Stehle, Gregor; Sava, Mihaela; Deigendesch, Nikolaus; Battegay, Manuel; Infanti, Laura; Holbro, Andreas; Bassetti, Stefano; Pargger, Hans; Hirsch, Hans H.; Leuzinger, Karoline; Kaiser, Laurent; Vu, Diem‐Lan; Baur, Katharina; Massaro, Nadine; Busch, Michael P.; Simmons, Graham; Stone, Mars; Felgner, Philip L.; Assis, Rafael Ramiro de; Khan, Saahir; Tsai, Cheng‐ting; Robinson, Peter V.; Seftel, David; Irsch, Johannes; Bagri, Anil; Buser, Andreas; Corash, Laurence

doi:10.1111/trf.17083

Cited by 8 publications

(5 citation statements)

References 86 publications

(200 reference statements)

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“…IgG3, and less predominantly IgG1, but not IgG2 and IgG4 were reported to contribute significantly to anti-SARS-CoV-2 neutralizing activity of CCP pools [13]. In previous studies little or no impact of AS treatment and MB treatment on neutralizing activity has been shown [20–22], which is in line with our findings of no significant impact of AS and MB treatment on IgG3. For RB treatment, where our data show no significant loss of IgG3 as well, conflicting observations have been reported with significant impact on neutralizing activity and antibody quantity in one side-by-side comparison study [21] and opposite results in another study [23].…”

Section: Discussionsupporting

confidence: 92%

The Impact of Pathogen Reduction on Total IgG and IgG Subclass Profiles of Convalescent Plasma

Wasiluk,

Sredzinska,

Rogowska

et al. 2023

Transfus Med Hemother

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Introduction: In case of newly emerging pathogens, convalescent plasma (CP) is often the only early available treatment option. It has been shown that different IgG subclasses contribute differently to CP neutralizing activity. As CP donors often have a risk profile like first-time donors, especially with respect to window-period viral transmission, pathogen reduction (PR) could mitigate that risk. The aim of our study, especially in the light of potential future pandemics, was to evaluate the impact of commercially available PR technologies on total IgG and IgG subclasses quantity and distribution in CP using COVID-19 CP (CCP) as surrogate for CP in a side-by-side comparison approach. Methods: 36 apheresis CCP donations were allocated to three study groups and a side-by-side assessment of the potential impact of amotosalen (AS)/UVA treatment compared to a riboflavin (RB)/UVB treatment, AS against methylene blue (MB) treatment, and RB against MB treatment on the quantity of IgG and IgG subclasses with a nephelometric analyzer was performed. Results: IgG subclass distributions were not significantly changed post PR treatment with all three technologies. There was also no significant difference in the median loss of concentration for IgG1 and IgG2 between the three technologies. We recognized a non-significant trend of a higher IgG4 median loss post RB treatment compared to post AS and MB treatment, respectively. Conclusion: Although the three commercially available PR systems do not significantly alter the distribution of IgG subclasses, we detected a non-significant trend of higher IgG4 loss after RB treatment. The potential impact of that finding needs further investigation.

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Section: Discussionsupporting

confidence: 92%

The Impact of Pathogen Reduction on Total IgG and IgG Subclass Profiles of Convalescent Plasma

Wasiluk,

Sredzinska,

Rogowska

et al. 2023

Transfus Med Hemother

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“…However, it also became evident that both the timing of plasma administration as well as the neutralizing antibody titer of the plasma administered are critical for patient outcome [ 49 , 50 , 51 ]. Studies have shown that the administration of plasma in very severe courses of COVID-19 is no longer beneficial and does not reduce mortality [ 51 , 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Early Treatment with Monoclonal Antibodies or Convalescent Plasma Reduces Mortality in Non-Vaccinated COVID-19 High-Risk Patients

Thümmler

Lindemann

Horn

et al. 2022

Viruses

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Vulnerable patients such as immunosuppressed or elderly patients are at high risk for a severe course of COVID-19 upon SARS-CoV-2 infection. Immunotherapy with SARS-CoV-2 specific monoclonal antibodies (mAb) or convalescent plasma represents a considerable treatment option to protect these patients from a severe or lethal course of infection. However, monoclonal antibodies are not always available or less effective against emerging SARS-CoV-2 variants. Convalescent plasma is more commonly available and may represent a good treatment alternative in low-income countries. We retrospectively evaluated outcomes in individuals treated with mAbs or convalescent plasma and compared the 30-day overall survival with a patient cohort that received supportive care due to a lack of SARS-CoV-2 specific therapies between March 2020 and April 2021. Our data demonstrate that mAb treatment is highly effective in preventing severe courses of SARS-CoV-2 infection. All patients treated with mAb survived. Treatment with convalescent plasma improved overall survival to 82% compared with 61% in patients without SARS-CoV-2 targeted therapy. Our data indicate that early convalescent plasma treatment may be an option to improve the overall survival of high-risk COVID-19 patients. This is especially true when other antiviral drugs are not available or their efficacy is significantly reduced, which may be the case with emerging SARS-CoV-2 variants.

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“…Convalescent COVID plasma (CCP) with high levels of neutralizing antibodies from recovered patients has demonstrated therapeutic efficacy to reduce the morbidity of COVID-19 disease in some studies. [3][4][5][6][7][8] However, other studies have questioned the efficacy of CCP to change the course of the disease. 9 In some studies, CCP may have been administered late in the course of the disease, or in small doses, and 20% of randomly selected CCP contain low levels of neutralizing antibodies.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of antibodies to SARS‐CoV‐2 in lyophilized plasma prepared with amotosalen‐UVA pathogen reduction

Martinaud,

Bagri,

Tsai

et al. 2023

Transfusion

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BackgroundSevere acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2)‐infected patients exhibit disease ranging from asymptomatic to severe pneumonia, multi‐organ failure, and death. convalescent COVID plasma (CCP) from recovered patients with high levels of neutralizing antibodies has demonstrated therapeutic efficacy to reduce the morbidity of coronavirus disease 2019 (COVID‐19) in some studies. The development of assays to characterize the activity of CCP to neutralize SARS‐CoV‐2 infectivity offers the possibility to improve potential therapeutic efficacy. Lyophilization of CCP may increase the availability of this therapy. We hypothesized that SARS‐CoV‐2 antibody profiles of pooled lyophilized pathogen‐reduced CCP from COVID‐19‐recovered blood donors retains virus‐neutralizing efficacy as reported for frozen pathogen‐reduced CCP.MethodsPooled lyophilized pathogen‐reduced plasma was prepared from recovered COVID plasma donors. Antibodies to SARS‐CoV‐2 were characterized in each donor plasma prior to pathogen reduction and lyophilization and after lyophilization of individual CCP, and in the lyophilized CCP pool. Several complimentary assays were used to characterize antibody levels, neutralizing capacity, and the spectrum of antigen reactivity. The mean values for individual plasma samples and the value in the pool were compared.ResultsThe mean ratio for antibody binding to SARS‐CoV‐2 antigens before and after treatment was 0.95 ± 0.22 mean fluorescent intensity (MFI) units. Antibody activity to an array of influenza virus antigens demonstrated a mean activity ratio of 0.92 ± 0.12 MFI before and after treatment.ConclusionsThe antibody activity in pooled pathogen‐reduced lyophilized CCPs demonstrated minimal impact due to pathogen reduction treatment and lyophilization.

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Characterization of pathogen‐inactivated COVID‐19 convalescent plasma and responses in transfused patients

Cited by 8 publications

References 86 publications

The Impact of Pathogen Reduction on Total IgG and IgG Subclass Profiles of Convalescent Plasma

The Impact of Pathogen Reduction on Total IgG and IgG Subclass Profiles of Convalescent Plasma

Early Treatment with Monoclonal Antibodies or Convalescent Plasma Reduces Mortality in Non-Vaccinated COVID-19 High-Risk Patients

Characterization of antibodies to SARS‐CoV‐2 in lyophilized plasma prepared with amotosalen‐UVA pathogen reduction

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