Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity

Immunity. 2020 Nov 17;53(5):925-933.e4. doi: 10.1016/j.immuni.2020.10.004. Epub 2020 Oct 14.

Abstract

We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection.

Keywords: COVID-19; S2 domain; SARS-CoV-2; antibodies; neutralization; nucleocapsid protein; orthogonal serological tests; receptor binding domain; serological test; serology; spike protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Arizona / epidemiology
  • Betacoronavirus / immunology*
  • Betacoronavirus / isolation & purification
  • COVID-19
  • COVID-19 Testing
  • Clinical Laboratory Techniques / methods*
  • Coronavirus Infections / blood
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / epidemiology*
  • Coronavirus Infections / immunology*
  • Coronavirus Nucleocapsid Proteins
  • Female
  • Humans
  • Immunity, Humoral*
  • Male
  • Middle Aged
  • Nucleocapsid Proteins / immunology
  • Pandemics
  • Phosphoproteins
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / epidemiology*
  • Pneumonia, Viral / immunology*
  • Prevalence
  • Protein Interaction Domains and Motifs
  • SARS-CoV-2
  • Seroepidemiologic Studies
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology
  • Young Adult

Substances

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