Viral Evolution and Immunology of SARS-CoV-2 in a Persistent Infection after Treatment with Rituximab

Viruses. 2022 Apr 3;14(4):752. doi: 10.3390/v14040752.

Abstract

Background: Prolonged shedding of SARS-CoV-2 in immunocompromised patients has been described. Furthermore, an accumulation of mutations of the SARS-CoV-2 genome in these patients has been observed.

Methods: We describe the viral evolution, immunologic response and clinical course of a patient with a lymphoma in complete remission who had received therapy with rituximab and remained SARS-CoV-2 RT-qPCR positive for 161 days.

Results: The patient remained hospitalised for 10 days, after which he fully recovered and remained asymptomatic. A progressive increase in Ct-value, coinciding with a progressive rise in lymphocyte count, was seen from day 137 onward. Culture of a nasopharyngeal swab on day 67 showed growth of SARS-CoV-2. Whole genome sequencing (WGS) demonstrated that the virus belonged to the wildtype SARS-CoV-2 clade 20B/GR, but rapidly accumulated a high number of mutations as well as deletions in the N-terminal domain of its spike protein.

Conclusion: SARS-CoV-2 persistence in immunocompromised individuals has important clinical implications, but halting immunosuppressive therapy might result in a favourable clinical course. The long-term shedding of viable virus necessitates customized infection prevention measures in these individuals. The observed accelerated accumulation of mutations of the SARS-CoV-2 genome in these patients might facilitate the origin of new VOCs that might subsequently spread in the general community.

Keywords: SARS-CoV-2; immunocompromised host; persistent infection; variants of concern (voc); viral evolution.

Publication types

  • Case Reports

MeSH terms

  • COVID-19 Drug Treatment*
  • Humans
  • Immunocompromised Host
  • Male
  • Persistent Infection
  • Rituximab / therapeutic use
  • SARS-CoV-2* / genetics

Substances

  • Rituximab