# Clonal interference and changing selective pressures shape the escape of SARS-CoV-2 from hundreds of antibodies

## TL;DR

This study shows how SARS-CoV-2 evolved to escape hundreds of antibodies through complex evolutionary processes like clonal interference and changing selective pressures.

## Contribution

The study uses deep mutational scanning data to reconstruct how SARS-CoV-2 escaped individual antibodies in nature over time.

## Key findings

- Escape levels for many antibodies fluctuated due to clade-turnover events.
- Fitness effects suggest mutations are displaced by clonal interference between clades.
- Changing selective pressures shaped the order in which escape mutations arose.

## Abstract

SARS-CoV-2 has evolved increased resistance to human polyclonal antibody responses. But, how it escaped individual monoclonal antibodies from these responses has not been thoroughly explored. Cao et al. used deep mutational scanning to identify mutations that allow SARS-CoV-2 to escape individual antibodies, doing so for hundreds of different antibodies. Here, we use these data to reconstruct how the virus escaped each antibody in nature. For each antibody, we predict how levels of escape changed in the global SARS-CoV-2 population over time. For many antibodies, these levels dramatically fluctuated due to escape mutations being displaced by clade-turnover events. We validate predicted patterns using pseudovirus neutralization data. Fitness effects estimated from natural sequences suggest that mutations are displaced due to clonal interference between clades and that the order in which mutations arose is shaped by changing selective pressures. Overall, this work suggests that SARS-CoV-2 evaded polyclonal responses via complex evolutionary dynamics.