COVID-19 adaptive humoral immunity models: weakly neutralizing versus antibody-disease enhancement scenarios

TL;DR

This paper develops a formal model to compare neutralizing, weakly neutralizing, and antibody-dependent enhancement scenarios in COVID-19 immunity, highlighting their different impacts on virus clearance and disease progression.

Contribution

It introduces a novel mathematical framework to distinguish between neutralizing and ADE effects in SARS-CoV-2 immune responses, supported by literature data.

Findings

Weakly neutralizing antibodies can lead to virus persistence or clearance.

Antibody-dependent enhancement can cause disease worsening or resolution.

Different immune dynamics are observed in each scenario.

Abstract

The interplay between the virus, infected cells and the immune responses to SARS-CoV-2 is still under debate. Extending the basic model of viral dynamics we propose here a formal approach to describe the neutralizing versus weakly (or non-)neutralizing scenarios and compare with the possible effects of antibody-dependent enhancement (ADE). The theoretical model is consistent with data available from the literature; we show that weakly neutralizing antibodies or ADE can both give rise to either final virus clearance or disease progression, but the immuno-dynamic is different in each case. Given that a significant part of the world population is already naturally immunized or vaccinated, we also discuss the implications on secondary infections infections following vaccination or in presence of immune system dysfunctions.