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Viral Evolution and Immunology of SARS-CoV-2 in a Persistent Infection after Treatment with Rituximab
Authors: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
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   persistent infection   immunocompromised host   variants of concern (voc)   viral evolution
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