Preexisting and de novo humoral immunity to SARS-CoV-2 in humans

TLDR

Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS‑CoV‑2 infection. Using diverse assays for antibodies recognizing SARS‑CoV‑2 proteins, we detected preexisting humoral immunity. SARS‑CoV‑2 spike‑protein reactive IgG antibodies were detected in uninfected individuals—especially children and adolescents—targeting mainly the S2 subunit, whereas infection induced higher titers of IgG against both S1 and S2, along with IgM and IgA, and neutralizing activity that persisted throughout the observation period.

Abstract

Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)-reactive antibodies were detectable using a flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the immunoglobulin G (IgG) class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.