Incomplete humoral response including neutralizing antibodies in asymptomatic to mild COVID-19 patients in Japan

Virology. 2021 Mar:555:35-43. doi: 10.1016/j.virol.2020.12.020. Epub 2021 Jan 6.

Abstract

The pandemic of COVID-19 is still ongoing, and many studies on serum antibodies have been reported, however, there are few studies about asymptomatic and mild patients. In this study, we enrolled 44 COVID-19 patients with relatively mild disease and 48 pre-pandemic controls. We measured serum antibodies against extracellular domain, S1 domain, and receptor-binding domain of Spike and N protein, examined neutralization titers by authentic virus neutralization assay and newly-developed bead/cell-based Spike-ACE2 inhibition assay, and compared them with clinical features. Most of these antibodies, including neutralizing titers, were mutually correlated, and the production of antibodies were associated with low Ct values of PCR test, disease severity, symptoms especially pneumonia, lymphopenia, and serological test including CRP, LD, D-dimer, and procalcitonin. Notably, 87.5% of asymptomatic and 23.5% of mild patients did not have antibody against SARS-CoV-2. Our results revealed the inadequate acquisition of humoral immunity in patients with asymptomatic and mild COVID-19 patients.

Keywords: Antibody; Asymptomatic; COVID-19; Clinical features; Disease severity; Immune response; Neutralizing assay; Neutralizing titer; SARS-CoV-2; Serological test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antibodies, Neutralizing / blood*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology
  • Asymptomatic Infections
  • COVID-19 / diagnosis
  • COVID-19 / immunology*
  • COVID-19 / physiopathology
  • COVID-19 Nucleic Acid Testing
  • Coronavirus Nucleocapsid Proteins / chemistry
  • Coronavirus Nucleocapsid Proteins / immunology*
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Japan
  • Male
  • Middle Aged
  • Phosphoproteins / chemistry
  • Phosphoproteins / immunology
  • Protein Domains
  • SARS-CoV-2 / immunology*
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Coronavirus Nucleocapsid Proteins
  • Immunoglobulin G
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2