Antigen-Specific Antibody Signature Is Associated with COVID-19 Outcome

Author:

Salgado Bárbara Batista1ORCID,Jordão Maele Ferreira1,de Morais Thiago Barros do Nascimento1,da Silva Danielle Severino Sena1,Pereira Filho Ivanildo Vieira1,Salgado Sobrinho Wlademir Braga1,Carvalho Nani Oliveira1,dos Santos Rafaella Oliveira1ORCID,Forato Julia2,Barbosa Priscilla Paschoal2,Toledo-Teixeira Daniel A.2ORCID,Pinto Kerollen Runa3,Correia Ingrid Silva3ORCID,Cordeiro Isabelle Bezerra3ORCID,Souza Neto Júlio Nino de3ORCID,Assunção Enedina Nogueira de3ORCID,Val Fernando Fonseca Almeida4,Melo Gisely Cardoso4,Sampaio Vanderson de Souza4ORCID,Monteiro Wuelton Marcelo4ORCID,Granja Fabiana5ORCID,Souza William M. de6,Astolfi Filho Spartaco3,Proenca-Modena Jose Luiz2ORCID,Lalwani Jaila Dias Borges7,Lacerda Marcus Vinícius Guimarães de14,Nogueira Paulo Afonso1ORCID,Lalwani Pritesh1ORCID

Affiliation:

1. Instituto Leônidas e Maria Deane (ILMD), Fiocruz Amazônia, Manaus 69000-000, Brazil

2. Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Insititute of Biology, University of Campinas (UNICAMP), Campinas 13000-000, Brazil

3. Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus 69000-000, Brazil

4. Fundação de Medicina Tropical, Doutor Heitor Vieira Dourado (FMT-HVD), Manaus 69000-000, Brazil

5. Centro de Estudos da Biodiversidade, Universidade Federal de Roraima (UFRR), Boa Vista 69300-000, Brazil

6. Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14000-000, Brazil

7. Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas (UFAM), Manaus 69000-000, Brazil

Abstract

Numerous studies have focused on inflammation-related markers to understand COVID-19. In this study, we performed a comparative analysis of spike (S) and nucleocapsid (N) protein-specific IgA, total IgG and IgG subclass response in COVID-19 patients and compared this to their disease outcome. We observed that the SARS-CoV-2 infection elicits a robust IgA and IgG response against the N-terminal (N1) and C-terminal (N3) region of the N protein, whereas we failed to detect IgA antibodies and observed a weak IgG response against the disordered linker region (N2) in COVID-19 patients. N and S protein-specific IgG1, IgG2 and IgG3 response was significantly elevated in hospitalized patients with severe disease compared to outpatients with non-severe disease. IgA and total IgG antibody reactivity gradually increased after the first week of symptoms. Magnitude of RBD-ACE2 blocking antibodies identified in a competitive assay and neutralizing antibodies detected by PRNT assay correlated with disease severity. Generally, the IgA and total IgG response between the discharged and deceased COVID-19 patients was similar. However, significant differences in the ratio of IgG subclass antibodies were observed between discharged and deceased patients, especially towards the disordered linker region of the N protein. Overall, SARS-CoV-2 infection is linked to an elevated blood antibody response in severe patients compared to non-severe patients. Monitoring of antigen-specific serological response could be an important tool to accompany disease progression and improve outcomes.

Funder

Fundação de Amparo à Pesquisa do Estado do Amazonas

Inova Fiocruz/Fundação Oswaldo Cruz grant

WHO Unity Studies

WHO by the COVID-19 Solidarity Response Fund and the German Federal Ministry of Health

São Paulo Research Foundation

Fundo de Apoio ao Ensino, Pesquisa e Extensão from UNICAMP

National Council for Scientific and Technological Development

ILMD/Fiocruz Amazônia

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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