Viral evolution and immunology of SARS-CoV-2 in a persistent infection after treatment with rituximab

Nathalie Van der Moeren, Philippe Selhorst, My Ha, Laura Heireman, Pieter-Jan Van Gaal, Dimitri Breems, Pieter Meysman, Kris Laukens, Walter Verstrepen, Natasja Van Gasse, Benson Ogunjimi, Kevin K Arien, Reinout Naesens

Research output: Contribution to journalA1: Web of Science-article


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.

Original languageEnglish
Issue number4
Publication statusPublished - 2022


  • COVID-19/drug therapy
  • Humans
  • Immunocompromised Host
  • Male
  • Persistent Infection
  • Rituximab/therapeutic use
  • SARS-CoV-2/genetics

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