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      Dynamics of antibodies to SARS‐CoV‐2 in convalescent plasma donors

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          Abstract

          Objectives

          Characterisation of the human antibody response to SARS‐CoV‐2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT‐PCR‐positive SARS‐CoV‐2 convalescent adults during the first 250 days after onset of symptoms.

          Methods

          We measured antibody responses to the receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT‐PCR‐positive SARS‐CoV‐2 convalescent adults. With a median of 5 (range 2–18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed‐effects modelling.

          Results

          All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow‐up analysis. Anti‐RBD IgG and anti‐nucleocapsid IgG levels declined with median half‐lives of 62 and 59 days, respectively, 2–5 months after symptom onset, and several‐fold variation in half‐lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow‐up, which points towards long‐term immunological memory. The magnitude of the anti‐RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in‐house developed competitive assay.

          Conclusion

          The result of this study gives valuable insight into the long‐term longitudinal response of antibodies to SARS‐CoV‐2.

          Abstract

          By measuring IgG concentrations at many time points per individual (844 samples for 151 subjects), we showed not only that the decline in IgG antibodies to SARS‐CoV‐2 occurs at substantially different rates between individuals, but also that rates of decline of antibody levels diminish as time progresses beyond 6 months, indicative of long‐term memory.

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          Most cited references48

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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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            Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

            A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
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              Antibody responses to SARS-CoV-2 in patients with COVID-19

              We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
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                Author and article information

                Contributors
                T.Rispens@sanquin.nl
                Journal
                Clin Transl Immunology
                Clin Transl Immunology
                10.1002/(ISSN)2050-0068
                CTI2
                Clinical & Translational Immunology
                John Wiley and Sons Inc. (Hoboken )
                2050-0068
                16 May 2021
                2021
                : 10
                : 5 ( doiID: 10.1002/cti2.v10.5 )
                : e1285
                Affiliations
                [ 1 ] Department of Immunopathology Sanquin Research Amsterdam The Netherlands
                [ 2 ] Landsteiner Laboratory Amsterdam University Medical Centre University of Amsterdam Amsterdam The Netherlands
                [ 3 ] Department of Experimental Immunohematology Sanquin Research and Landsteiner Laboratory Amsterdam University Medical Centre Amsterdam The Netherlands
                [ 4 ] Department of Infectious Diseases Public Health Service region Utrecht Utrecht The Netherlands
                [ 5 ] Department of Virology Sanquin Diagnostic Services Amsterdam The Netherlands
                [ 6 ] Sanquin Blood Supply Foundation and Amsterdam University Medical Centre Amsterdam The Netherlands
                [ 7 ] Sanquin Blood Bank Unit Transfusion Medicine Leiden The Netherlands
                [ 8 ] Department of Transfusion Medicine Sanquin Blood Bank Amsterdam The Netherlands
                [ 9 ] Department of Medical Microbiology Amsterdam UMC University of Amsterdam Amsterdam The Netherlands
                [ 10 ] Virology Division Department of Infectious Diseases and Immunology Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands
                Author notes
                [*] [* ] Correspondence

                T Rispens, Department of Immunopathology, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.

                E‐mail: T.Rispens@ 123456sanquin.nl

                Author information
                https://orcid.org/0000-0001-9600-1312
                Article
                CTI21285
                10.1002/cti2.1285
                8126762
                34026115
                2539f222-96c5-4672-97ff-675d1689f126
                © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 April 2021
                : 29 January 2021
                : 15 April 2021
                Page count
                Figures: 5, Tables: 1, Pages: 12, Words: 6749
                Funding
                Funded by: ZonMw , open-funder-registry 10.13039/501100001826;
                Award ID: 10430 01 201 0012
                Funded by: European Commission , open-funder-registry 10.13039/501100000780;
                Award ID: 101015756
                Categories
                Original Article
                Original Article
                Custom metadata
                2.0
                2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:17.05.2021

                ace2‐competitive elisa,antibodies,covid‐19,longitudinal,neutralisation

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