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      Infection induced SARS-CoV-2 seroprevalence and heterogeneity of antibody responses in a general population cohort study in Catalonia Spain

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          Abstract

          Sparse data exist on the complex natural immunity to SARS-CoV-2 at the population level. We applied a well-validated multiplex serology test in 5000 participants of a general population study in Catalonia in blood samples collected from end June to mid November 2020. Based on responses to fifteen isotype-antigen combinations, we detected a seroprevalence of 18.1% in adults (n = 4740), and modeled extrapolation to the general population of Catalonia indicated a 15.3% seroprevalence. Antibodies persisted up to 9 months after infection. Immune profiling of infected individuals revealed that with increasing severity of infection (asymptomatic, 1–3 symptoms, ≥ 4 symptoms, admitted to hospital/ICU), seroresponses were more robust and rich with a shift towards IgG over IgA and anti-spike over anti-nucleocapsid responses. Among seropositive participants, lower antibody levels were observed for those ≥ 60 years vs < 60 years old and smokers vs non-smokers. Overweight/obese participants vs normal weight had higher antibody levels. Adolescents (13–15 years old) (n = 260) showed a seroprevalence of 11.5%, were less likely to be tested seropositive compared to their parents and had dominant anti-spike rather than anti-nucleocapsid IgG responses. Our study provides an unbiased estimate of SARS-CoV-2 seroprevalence in Catalonia and new evidence on the durability and heterogeneity of post-infection immunity.

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          Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

          The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.
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            Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

            Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
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              Evolution of antibody immunity to SARS-CoV-2

              Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
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                Author and article information

                Contributors
                marianna.karachaliou@isglobal.org
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                3 November 2021
                3 November 2021
                2021
                : 11
                : 21571
                Affiliations
                [1 ]GRID grid.434607.2, ISNI 0000 0004 1763 3517, Barcelona Institute for Global Health (ISGlobal), ; 08036 Barcelona, Spain
                [2 ]GRID grid.452366.0, ISNI 0000 0000 9638 9567, Centro de Investigação em Saúde de Manhiça (CISM), ; Maputo, Mozambique
                [3 ]GRID grid.466571.7, ISNI 0000 0004 1756 6246, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), ; 08036 Madrid, Spain
                [4 ]GRID grid.429186.0, Genomes for Life-GCAT Lab, , Institute for Health Science Research Germans Trias i Pujol (IGTP), ; Badalona, Spain
                [5 ]GRID grid.438280.5, Banc de Sang i Teixits (BST), ; Barcelona, Spain
                [6 ]GRID grid.5612.0, ISNI 0000 0001 2172 2676, Universitat Pompeu Fabra (UPF), ; Barcelona, Spain
                [7 ]GRID grid.36083.3e, ISNI 0000 0001 2171 6620, Faculty of Health Sciences, , Universitat Oberta de Catalunya, ; Barcelona, Spain
                [8 ]GRID grid.418701.b, ISNI 0000 0001 2097 8389, Unit of Molecular and Genetic Epidemiology in Infections and Cancer (UNIC-Molecular), Cancer Epidemiology Research Programme, IDIBELL, , Catalan Institute of Oncology, ; Hospitalet De Llobregat, Spain
                [9 ]GRID grid.20522.37, ISNI 0000 0004 1767 9005, Hospital del Mar Medical Research Institute (IMIM), ; 08003 Barcelona, Spain
                Article
                807
                10.1038/s41598-021-00807-4
                8566562
                34732749
                800eee5b-0f88-4146-9019-ebd784bd701b
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 May 2021
                : 12 October 2021
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                © The Author(s) 2021

                Uncategorized
                viral infection,epidemiology,risk factors
                Uncategorized
                viral infection, epidemiology, risk factors

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