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      The role of convalescent plasma and hyperimmune immunoglobulins in the COVID-19 pandemic, including implications for future preparedness

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          Abstract

          Introduction

          When Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks.

          Methods

          A scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment. This review included the latest Cochrane systematic review update on 30-day mortality and safety. We also covered use in pediatric and immunocompromised patients, as well as the logistic challenges faced in donor recruitment and plasma collection in general. Challenges for low resource countries were specifically highlighted.

          Results

          A major challenge is the high donation frequency required from first-time donors to ensure a safe product, which minimizes the risk of transfusion-transmitted infectious. This is particularly difficult in low- and middle- income countries due to inadequate infrastructure and insufficient blood product supplies. High-certainty evidence indicates that convalescent plasma does not reduce mortality or significantly improve clinical outcomes in patients with moderate to severe COVID-19 infection. However, CCP may provide a viable treatment for patients unable to mount an endogenous immune response to SARS-CoV-2, based on mostly observational studies and subgroup data of published and ongoing randomized trials. Convalescent plasma has been shown to be safe in adults and children with COVID-19 infection. However, the efficacy in pediatric patients remains unclear.

          Discussion

          Data on efficacy and safety of CCP are still underway in ongoing (randomized) studies and by reporting the challenges, limitations and successes encountered to-date, research gaps were identified to be addressed for the future.

          Conclusion

          This experience serves as a valuable example for future pandemic preparedness, particularly when therapeutic options are limited, and vaccines are either being developed or ineffective due to underlying immunosuppression.

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          Most cited references119

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

              Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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                Author and article information

                Contributors
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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                09 September 2024
                2024
                : 15
                : 1448720
                Affiliations
                [1] 1 Department Transfusion Medicine, Division Blood Bank, Sanquin Blood Supply Foundation , Amsterdam, Netherlands
                [2] 2 Department Hematology, Erasmus Medical Centre , Rotterdam, Netherlands
                [3] 3 Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University , Taipei, Taiwan
                [4] 4 International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University , Taipei, Taiwan
                [5] 5 Department of Hematology, Sultan Qaboos University Hospital , Muscat, Oman
                [6] 6 Department of Pathology, Johns Hopkins University School of Medicine , Baltimore, MD, United States
                [7] 7 Radcliffe Department of Medicine, University of Oxford and National Health Service (NHS) Blood and Transplant , Oxford, United Kingdom
                [8] 8 Division of Hematology/Oncology, Simmons Cancer Institute at Southern Illinois University (SIU) School of Medicine , Springfield, IL, United States
                [9] 9 Dept Corporate Medical Affairs, Vitalant Corporate Medical Affairs , Scottsdale, AZ, United States
                [10] 10 Etablissement Français du Sang, La Plaine-St-Denis and Université de Franche-Comté , Besançon, France
                [11] 11 Department of Transfusion Medicine and Technical Services, The South African National Blood Service , Roodepoort, South Africa
                [12] 12 Dept Transfusion Medicine, Hospital Sírio-Libanês Blood Bank , São Paulo, Brazil
                [13] 13 Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University , Melbourne, VIC, Australia
                [14] 14 Department of Clinical Haematology, Monash Health , Melbourne, VIC, Australia
                Author notes

                Edited by: Valentina Mazzotta, National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), Italy

                Reviewed by: Narayanaiah Cheedarla, Emory University, United States

                Valeria De Giorgi, National Institutes of Health (NIH), United States

                *Correspondence: Cynthia So-Osman, c.so@ 123456sanquin.nl

                †ORCID: Cynthia So-Osman, orcid.org/0000-0003-4151-2865; Thierry Burnouf, orcid.org/0000-0002-0507-9243; Arwa Z. Al-Riyami, orcid.org/0000-0001-8649-0650; Evan M. Bloch, orcid.org/0000-0001-8181-9517; Lise Estcourt, orcid.org/0000-0003-4309-9162; Ruchika Goel, orcid.org/0000-0001-9653-9905; Pierre Tiberghien, orcid.org/0000-0002-9310-8322; Marion Vermeulen, orcid.org/0000-0003-4383-4526; Silvano Wendel, orcid.org/0000-0002-1941-7733; Erica M. Wood, orcid.org/0000-0001-7527-2340

                Article
                10.3389/fimmu.2024.1448720
                11416983
                39315108
                e1eb4949-9434-46d9-8f0b-3ad9bc0b4a60
                Copyright © 2024 So-Osman, Burnouf, Al-Riyami, Bloch, Estcourt, Goel, Tiberghien, Vermeulen, Wendel and Wood

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 June 2024
                : 21 August 2024
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 124, Pages: 13, Words: 6697
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Immunology
                Review
                Custom metadata
                Viral Immunology

                Immunology
                covid-19,sars-cov-2,convalescent plasma,scoping review,clinical use,plasma collection,adult,pediatric

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