# HKU1 immune imprinting is associated with post-COVID symptoms after SARS-CoV-2 infection

## TL;DR

This study explores how prior immunity to common coronaviruses like HKU1 may influence post-COVID symptoms after SARS-CoV-2 infection and vaccination.

## Contribution

The study reveals a novel link between HKU1 immune imprinting and increased post-COVID symptoms through Fc-mediated inflammation.

## Key findings

- SARS-CoV-2 vaccination recalls low-avidity antibodies to β-human coronaviruses like HKU1.
- HKU1 cross-reactive antibodies enhance Fc-mediated effector functions and are linked to post-COVID symptoms.
- Higher HKU1 IgG levels correlate with increased post-COVID symptoms in vaccinated individuals.

## Abstract

The long-term health burden of SARS-CoV-2 infections remains poorly understood. In a cohort from Vancouver, Canada, we identified immune imprinting to endemic β-human coronaviruses (HCoVs), reflected by affinity-matured IgG responses that cross-reacted with the SARS-CoV-2 spike with low affinity, along with an early expansion of memory B cells recognizing HKU1 and the conserved S2 domain following the first dose of ancestral-strain vaccination. Vaccination also enhanced antibody-dependent cellular phagocytosis (ADCP), primarily directed against the HKU1 spike and SARS-CoV-2 S2 domains. In another cohort from the same region, higher HKU1 spike IgG levels and increased antibody-dependent complement deposition (ADCD) were associated with a greater likelihood of post-COVID symptoms, even though these individuals had experienced fewer SARS-CoV-2 infections at the one-year follow-up. Together, these findings suggest that β-HCoV-associated immune imprinting may simultaneously reduce infection risk and promote pathological Fc-mediated inflammation, potentially contributing to post-COVID conditions following infection with contemporary SARS-CoV-2 variants in individuals vaccinated against earlier strains.

•SARS-CoV-2 vaccination recalls low-avidity human β-coronaviruses antibodies•The recalled B cells preferentially target conserved epitopes on the S2 domain•HKU1 cross-reactive antibodies show enhanced Fc-mediated effector function•These antibodies increased post-COVID symptoms in two independent cohorts

SARS-CoV-2 vaccination recalls low-avidity human β-coronaviruses antibodies

The recalled B cells preferentially target conserved epitopes on the S2 domain

HKU1 cross-reactive antibodies show enhanced Fc-mediated effector function

These antibodies increased post-COVID symptoms in two independent cohorts

Health sciences; Medicine; Immunology; Virology