# Viral clearance and escape during therapy of COVID-19 outpatients: A prospective cohort study

## TL;DR

This study finds that suboptimal antibody treatments in immunocompromised patients increase the risk of SARS-CoV-2 escape mutations, suggesting direct antivirals like nirmatrelvir are better alternatives.

## Contribution

The study identifies factors driving viral clearance and escape mutations in immunocompromised patients treated with monoclonal antibodies or antivirals.

## Key findings

- Baseline viral load, neutralization, and therapy determine viral clearance outcomes.
- Low neutralization and poor viral clearance are linked to the emergence of antibody-escape mutations.
- Spike mutations occur in immunocompromised patients treated with suboptimal monoclonal antibodies.

## Abstract

The efficacy of neutralizing SARS-CoV-2 monoclonal antibodies (mAbs) in preventing severe COVID-19 has been hindered by the diversity of viral strains and the complexity of patient populations. In this prospective cohort study, we used regression analyses to identify virological, immunological, and clinical factors associated with viral clearance and emergence of escape mutations. We included 114 mainly immunocompromised high-risk patients with mild-to-moderate COVID-19 who received mAbs or direct antivirals to prevent COVID-19 progression. Nasopharyngeal SARS-CoV-2 RNA level at day 7 was independently associated with viral load at day 0, serum neutralization at day 7, and treatment received. The emergence of mutations within Spike was observed in 21.9% of patients, all being immunocompromised treated by Sotrovimab or Tixagevimab/Cilgavimab after Omicron emergence, and was independently associated with higher viral load and serum neutralization at day 7. Our data show that suboptimal neutralizing antibodies should be avoided in immunocompromised individuals, given the risk of emergence of viral escape mutations.

•Baseline viral load, neutralization, and therapy govern viral clearance•Poor viral clearance and low neutralization drive antibody-escape mutant emergence•Spike mutations emerge in immunocompromised patients treated with suboptimal antibodies•In immunocompromised patients, nirmatrelvir should be used instead of suboptimal antibodies

Baseline viral load, neutralization, and therapy govern viral clearance

Poor viral clearance and low neutralization drive antibody-escape mutant emergence

Spike mutations emerge in immunocompromised patients treated with suboptimal antibodies

In immunocompromised patients, nirmatrelvir should be used instead of suboptimal antibodies

Immunology; Virology; Public health