*Case Report* **A Case of a Malignant Lymphoma Patient Persistently Infected with SARS-CoV-2 for More than 6 Months**

**Yoji Nagasaki 1,\*, Masanori Kadowaki 2, Asako Nakamura 3, Yoshiki Etoh 3, Masatoshi Shimo 2, Sayoko Ishihara 1, Yoko Arimizu 1, Rena Iwamoto 4, Seiji Kamamuta <sup>4</sup> and Hiromi Iwasaki <sup>2</sup>**


**Abstract:** Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome 2 (SARS-CoV-2). There are many unknowns regarding the handling of long-term SARS-CoV-2 infections in immunocompromised patients. Here, we describe the lethal disease course in a SARS-CoV-2-infected patient during Bruton's tyrosine kinase inhibitor therapy. We performed whole-genome analysis using samples obtained during the course of the disease in a 63-year-old woman who was diagnosed with intraocular malignant lymphoma of the right eye in 2012. She had received treatment since the diagnosis. An autologous transplant was performed in 2020, but she experienced a worsening of the primary disease 26 days before she was diagnosed with a positive SARS-CoV-2 RT-PCR. Tirabrutinib was administered for the primary disease. A cluster of COVID-19 infections occurred in the hematological ward while the patient was hospitalized, and she became infected on day 0. During the course of the disease, she experienced repeated remission exacerbations of COVID-19 pneumonia and eventually died on day 204. SARS-CoV-2 whole-viral sequencing revealed that the patient shed the virus long-term. Viral infectivity studies confirmed infectious virus on day 189, suggesting that the patient might be still infectious. This case report describes the duration and viral genetic evaluation of a patient with malignant lymphoma who developed SARS-CoV-2 infection during Bruton's tyrosine kinase inhibitor therapy and in whom the infection persisted for over 6 months.

**Keywords:** SARS-CoV-2; immunocompromised host; Bruton's tyrosine kinase; persistent infection
