Distinct Early Serological Signatures Track with SARS-CoV-2 Survival

Immunity. 2020 Sep 15;53(3):524-532.e4. doi: 10.1016/j.immuni.2020.07.020. Epub 2020 Jul 30.


As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection, whereas others rapidly progress and die. Although the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point to immunological mechanisms of protection. Here, we profiled SARS-CoV-2-specific humoral responses in a cohort of 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures resolved individuals with different outcomes. Although no differences in SARS-CoV-2-specific IgG levels were observed, spike-specific humoral responses were enriched among convalescent individuals, whereas functional antibody responses to the nucleocapsid were elevated in deceased individuals. Furthermore, this enriched immunodominant spike-specific antibody profile in convalescents was confirmed in a larger validation cohort. These results demonstrate that early antigen-specific and qualitative features of SARS-CoV-2-specific antibodies point to differences in disease trajectory, highlighting the potential importance of functional antigen-specific humoral immunity to guide patient care and vaccine development.

Keywords: COVID-19 patients; SARS-CoV-2; SARS-CoV-2-specific antibody; functional antibody.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood*
  • Betacoronavirus / immunology
  • COVID-19
  • Coronavirus Infections / blood
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / mortality*
  • Coronavirus Nucleocapsid Proteins
  • Female
  • Humans
  • Immunity, Humoral / immunology
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Nucleocapsid Proteins / immunology*
  • Pandemics
  • Phosphoproteins
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / mortality*
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / immunology*


  • Antibodies, Viral
  • Coronavirus Nucleocapsid Proteins
  • Immunoglobulin G
  • Nucleocapsid Proteins
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2