Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the COVID-19 pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 204 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 252 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ~23% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but paradoxically these hCoV cross-reactive antibodies were boosted upon SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; antibody; coronavirus.

Figure 1.. Identification of pre-existing cross-reactive SARS-CoV-2 antibodies in human serum prior to the pandemic.

ELISAs were completed to quantify levels of serum antibodies binding to the SARS-CoV-2 full-length spike (S) protein (A), the receptor binding domain (S-RBD) of S (B), and the nucleocapsid (N) protein (C); dashed line denotes lower limit of detection (LOD=50), dotted line represents a threshold set 2-fold above LOD (>100). We tested samples collected from 204 individuals in the summer of 2017, prior to the global pandemic. We also tested samples collected from 15 individuals following confirmed SARS-CoV-2 infections. and recovered adults. (D) The relationship between antibody titers in donors with detectable IgG against the S-RBD and/or full length S is shown. (E) SARS-CoV-2 pseudotype neutralization assays were completed using pre-pandemic serum samples with (n=9) and without (n=22) cross reactive SARS-CoV-2 antibodies, as well as serum samples from individuals following confirmed SARS-CoV-2 infections (n=15); one-way ANOVA Tukey’s multiple comparisons of log2 transformed antibody titers ****p<0.0001; dotted line denotes lower LOD (=10). (F–H) ELISAs were completed to quantify levels of serum antibodies binding to the full length S proteins from 229E, NL63, and OC43 using pre-pandemic serum samples with (n=12) and without (n=51). Unpaired t-tests of log2 transformed antibody titers ****p<0.0001 and **p=0.0027. Horizontal lines indicate geometric mean and error bars represent standard deviation.

Figure 2.. Pre-pandemic SARS-CoV-2 and OC43-reactive antibodies are not associated with protection from SARS-CoV-2 infection.

We quantified antibody levels in pre-pandemic serum samples collected from individuals who later became SARS-CoV-2 infected (cases; n=251) and those who did not become SARS-CoV-2 infected (controls; n=251). ELISAs were completed to quantify levels of antibodies reactive to SARS-CoV-2 proteins (S, S-RBD, and N) and the OC43 S protein. Shown are data using samples collected from the entire cohort between August 2013 and March 2020 (A) and samples from a smaller subset of individuals collected between April 2019-Mach 2020 (B). Antibody titers between cases and controls were not significantly different as determined by unpaired t-tests of log2 transformed antibody titers. Dashed line denotes lower limit of detection (LOD=50), dotted line represents a threshold set 2-fold above LOD (>100).

Figure 3.. SARS-CoV-2 infections boost antibodies that react to OC43 S protein.

We quantified antibody levels in serum collected from 27 individuals 0 and 7 days after hospitalization for COVID-19. ELISAs were completed to quantify levels of antibodies reactive to the S proteins of 229E, NL63, OC43 and SARS-CoV-2. (A) IgG titers and (B) titer fold change are shown. (C) Fold change in OC43 S-reactive antibodies was not associated with disease outcome. Paired t-test of log2 transformed antibody titers, ****p<0.0001. One-way ANOVA Tukey’s multiple comparisons fold-change in antibody titers, *p<0.04. Horizontal lines indicate the mean and error bars show standard deviation.