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1.
Immunity ; 55(6): 998-1012.e8, 2022 06 14.
Article in English | MEDLINE | ID: covidwho-1778212

ABSTRACT

SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for antibodies. Here, we use NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated. We found 6 complementation groups of neutralizing antibodies. 58% targeted epitopes outside the NTD supersite, 58% neutralized either Gamma or Omicron, and 14% were broad neutralizers that also neutralized Omicron. Structural characterization revealed that broadly active antibodies targeted three epitopes outside the NTD supersite including a class that recognized both the NTD and SD2 domain. Rapid recruitment of memory B cells producing these antibodies into the plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants, including Omicron.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Epitopes , Humans , Memory B Cells , SARS-CoV-2
2.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327330

ABSTRACT

Summary SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for the antibody system. Neutralizing antibodies targeting the RBD bind to several different sites on this domain. In contrast, most neutralizing antibodies to NTD characterized to date bind to a single supersite, however these antibodies were obtained by methods that were not NTD specific. Here we use NTD specific probes to focus on anti-NTD memory B cells in a cohort of pre-omicron infected individuals some of which were also vaccinated. Of 275 NTD binding antibodies tested 103 neutralized at least one of three tested strains: Wuhan-Hu-1, Gamma, or PMS20, a synthetic variant which is extensively mutated in the NTD supersite. Among the 43 neutralizing antibodies that were further characterized, we found 6 complementation groups based on competition binding experiments. 58% targeted epitopes outside the NTD supersite, and 58% neutralized either Gamma or Omicron, but only 14% were broad neutralizers. Three of the broad neutralizers were characterized structurally. C1520 and C1791 recognize epitopes on opposite faces of the NTD with a distinct binding pose relative to previously described antibodies allowing for greater potency and cross-reactivity with 7 different variants including Beta, Delta, Gamma and Omicron. Antibody C1717 represents a previously uncharacterized class of NTD-directed antibodies that recognizes the viral membrane proximal side of the NTD and SD2 domain, leading to cross-neutralization of Beta, Gamma and Omicron. We conclude SARS-CoV-2 infection and/or Wuhan-Hu-1 mRNA vaccination produces a diverse collection of memory B cells that produce anti-NTD antibodies some of which can neutralize variants of concern. Rapid recruitment of these cells into the antibody secreting plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants including omicron.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-306082

ABSTRACT

Objective: The rapid development of coronavirus disease 2019 (COVID-19) into a pandemic required people to quickly acquire, evaluate, and apply novel complex health-related information about the virus and transmission risks. This study examined the possible interplay between neurocognition and health literacy in the early uptake and use of COVID-19 public health information. Method: Data were collected between April 23 and May 21, 2020, a period during which 42 out of 50 states were under a stay-at-home order. Participants were 217 healthy adults who completed a telephone-based battery that included standard tests of neurocognition, health literacy, verbal IQ, personality, and anxiety. Participants also completed measures of COVID-19 information-seeking skills, knowledge, prevention intentions, and prevention behaviors. Results: A series of hierarchical multiple regressions with data-driven covariates showed that neurocognition (viz, episodic verbal memory and executive functions) was independently related to COVID-19 knowledge (e.g., symptoms, risks) at a medium effect size, but not to information-seeking skills, prevention intentions, or prevention behaviors. Health literacy was independently related to all measured aspects of COVID-19 health information and did not interact with neurocognition in any COVID-19 health domain. Conclusions: Individual differences in neurocognition and health literacy played independent and meaningful roles in the initial acquisition of knowledge related to COVID-19, which is a novel human health condition. Future studies might examine whether neurocognitive supports (e.g., spaced retrieval practice, elaboration) can improve COVID-19-related knowledge and health behaviors in vulnerable populations.

4.
J Clin Exp Neuropsychol ; 43(5): 497-513, 2021 07.
Article in English | MEDLINE | ID: covidwho-1272921

ABSTRACT

Introduction: The rapid development of coronavirus disease 2019 (COVID-19) into a pandemic required people to quickly acquire, evaluate, and apply novel complex health-related information about the virus and transmission risks. This study examined the potentially unique and synergistic roles of individual differences in neurocognition and health literacy in the early uptake and use of COVID-19 public health information.Method: Data were collected between April 23 and 21 May 2020, a period during which 42 out of 50 states were under a stay-at-home order. Participants were 217 healthy adults who completed a telephone-based battery that included standard tests of neurocognition, health literacy, verbal IQ, personality, and anxiety. Participants also completed measures of COVID-19 information-seeking skills, knowledge, prevention intentions, and prevention behaviors.Results: A series of hierarchical multiple regressions with data-driven covariates showed that neurocognition (viz, episodic verbal memory and executive functions) was independently related to COVID-19 knowledge (e.g. symptoms, risks) at a medium effect size, but not to information-seeking skills, prevention intentions, or prevention behaviors. Health literacy was independently related to all measured aspects of COVID-19 health information and did not interact with neurocognition in any COVID-19 health domain.Conclusions: Individual differences in neurocognition and health literacy played independent and meaningful roles in the initial acquisition of knowledge related to COVID-19, which is a novel human health condition. Future studies might examine whether neurocognitive supports (e.g. spaced retrieval practice, elaboration) can improve COVID-19-related knowledge and health behaviors in vulnerable populations.


Subject(s)
COVID-19 , Health Behavior , Health Knowledge, Attitudes, Practice , Health Literacy , Individuality , Adolescent , Adult , Aged , COVID-19/epidemiology , Cross-Sectional Studies , Female , Health , Humans , Male , Middle Aged , SARS-CoV-2 , Young Adult
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