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SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity.

ABSTRACT: The protective effect of neutralizing antibodies in SARS-CoV-2 infected individuals is not yet well defined. To address this issue, we have analyzed the kinetics of neutralizing antibody responses and their association with disease severity. Between March and May 2020, the prospective KING study enrolled 72 COVID-19+ participants grouped according to disease severity. SARS-CoV-2 infection was diagnosed by serological and virological tests. Plasma neutralizing responses were assessed against replicative virus and pseudoviral particles. Multiple regression and non-parametric tests were used to analyze dependence of parameters. The magnitude of neutralizing titers significantly increased with disease severity. Hospitalized individuals developed higher titers compared to mild-symptomatic and asymptomatic individuals, which together showed titers below the detection limit in 50% of cases. Longitudinal analysis confirmed the strong differences in neutralizing titers between non-hospitalized and hospitalized participants and showed rapid kinetics of appearance of neutralizing antibodies (50% and 80% of maximal activity reached after 11 and 17 days after symptoms onset, respectively) in hospitalized patients. No significant impact of age, gender or treatment on the neutralizing titers was observed in this limited cohort. These data identify a clear association of humoral immunity with disease severity and point to immune mechanisms other than antibodies as relevant players in COVID-19 protection.

SUBMITTER: Trinite B

PROVIDER: S-EPMC7843981 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity.

Trinité Benjamin B Tarrés-Freixas Ferran F Rodon Jordi J Pradenas Edwards E Urrea Víctor V Marfil Silvia S Rodríguez de la Concepción María Luisa ML Ávila-Nieto Carlos C Aguilar-Gurrieri Carmen C Barajas Ana A Ortiz Raquel R Paredes Roger R Mateu Lourdes L Valencia Alfonso A Guallar Víctor V Ruiz Lidia L Grau Eulàlia E Massanella Marta M Puig Jordi J Chamorro Anna A Izquierdo-Useros Nuria N Segalés Joaquim J Clotet Bonaventura B Carrillo Jorge J Vergara-Alert Júlia J Blanco Julià J

Scientific reports 20210128 1

The protective effect of neutralizing antibodies in SARS-CoV-2 infected individuals is not yet well defined. To address this issue, we have analyzed the kinetics of neutralizing antibody responses and their association with disease severity. Between March and May 2020, the prospective KING study enrolled 72 COVID-19+ participants grouped according to disease severity. SARS-CoV-2 infection was diagnosed by serological and virological tests. Plasma neutralizing responses were assessed against repl ...[more]

PMID: 33510275

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Project description:Measuring the adaptive immune response to SARS-CoV-2 can enable the assessment of past infection as well as protective immunity and the risk of reinfection. While neutralizing antibody (nAb) titers are one measure of protection, such assays are challenging to perform at a large scale and the longevity of the SARS-CoV-2 nAb response is not fully understood. Here, we apply a T-cell receptor (TCR) sequencing assay that can be performed on a small volume standard blood sample to assess the adaptive T-cell response to SARS-CoV-2 infection. Samples were collected from a cohort of 302 individuals recovered from COVID-19 up to 6 months after infection. Previously published findings in this cohort showed that two commercially available SARS-CoV-2 serologic assays correlate well with nAb testing. We demonstrate that the magnitude of the SARS-CoV-2-specific T-cell response strongly correlates with nAb titer, as well as clinical indicators of disease severity including hospitalization, fever, or difficulty breathing. While the depth and breadth of the T-cell response declines during convalescence, the T-cell signal remains well above background with high sensitivity up to at least 6 months following initial infection. Compared to serology tests detecting binding antibodies to SARS-CoV-2 spike and nucleoprotein, the overall sensitivity of the TCR-based assay across the entire cohort and all timepoints was approximately 5% greater for identifying prior SARS-CoV-2 infection. Notably, the improved performance of T-cell testing compared to serology was most apparent in recovered individuals who were not hospitalized and were sampled beyond 150 days of their initial illness, suggesting that antibody testing may have reduced sensitivity in individuals who experienced less severe COVID-19 illness and at later timepoints. Finally, T-cell testing was able to identify SARS-CoV-2 infection in 68% (55/81) of convalescent samples having nAb titers below the lower limit of detection, as well as 37% (13/35) of samples testing negative by all three antibody assays. These results demonstrate the utility of a TCR-based assay as a scalable, reliable measure of past SARS-CoV-2 infection across a spectrum of disease severity. Additionally, the TCR repertoire may be useful as a surrogate for protective immunity with additive clinical value beyond serologic or nAb testing methods.

Project description:BackgroundThe recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees.MethodsSamples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant.ResultsIn patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant.ConclusionsRepeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.

Dataset Information

SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity.

Publications

SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity.

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