Garrido et al.
May 31, 2022
This study investigates how IgG responses to the SARS-CoV-2 spike protein, particularly those targeting conserved regions from seasonal coronaviruses (shCoVs), influence COVID-19 disease severity.
This study investigates how IgG responses to the SARS-CoV-2 spike protein, particularly those targeting conserved regions from seasonal coronaviruses (shCoVs), influence COVID-19 disease severity. The authors analyzed anti-spike IgG levels, epitope targeting, and their correlation with disease outcomes in non-hospitalized convalescent individuals, revealing that:
Higher Disease Severity: Severe COVID-19 was associated with elevated anti-spike IgG levels and greater cross-reactivity with other betacoronaviruses (b-CoVs), such as OC43 and SARS-CoV-1. IgG targeting the S20 fusion peptide (S20FP) was strongly linked to severe disease.
Milder Disease: Milder cases had higher IgG responses targeting the HR2 region of the spike, suggesting that these responses could be protective. The ratio of IgG targeting HR2 to S20FP was particularly predictive of disease severity.
FcgR Activation: Fcg receptor activation (which mediates non-neutralizing antibody functions like ADCC) was higher in severe cases and correlated with specific epitope targets, like S20FP and CTD1 regions. This suggests that the activation of these pathways could exacerbate the disease.
The study concludes that pre-existing immune memory to seasonal coronaviruses, particularly cross-reactive IgG responses targeting the SARS-CoV-2 spike, may influence COVID-19 outcomes. These findings also highlight the potential of epitope-specific IgG profiles to predict disease severity, offering insight into how past exposure to seasonal coronaviruses may affect immune responses to SARS-CoV-2.