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

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.

Radiologic Abnormalities in Prolonged SARS-CoV-2 Infection: A Systematic Review

“…Interestingly, all patients who had used anti-CD20 agents within one year exhibited migration of airspace opacities during SARS-CoV-2 infection. Three additional patients who showed migratory pneumonia during SARS-CoV-2 infection had either X-linked agammaglobulinemia (XLA) [ 14 ], which is a condition characterized by an inability to produce B-cells, or were undergoing treatment with tirabrutinib [ 21 ], a Bruton’s tyrosine kinase (BTK) inhibitor that inhibits pathways associated with B-cell proliferation and development. In fact, BTK is known to be defective in XLA [ 33 ], and one study revealed that the pooled antibody responses after COVID-19 vaccination were the lowest (15% and 23%, respectively) for patients who had used anti-CD20 therapy within one year prior to COVID-19 diagnosis and a BTK inhibitor [ 34 ].…”

“…Although the mechanism is not clear, a flawed immune-mediated reaction in conjunction with persistent viral shedding into the lungs despite some clearance of the viruses may be responsible for the development of migratory airspace opacities. Depletion of B-cells may protect the patients from a cytokine storm and severe pneumonia due to dampened inflammatory responses, but the inability to eliminate the virus from the body may result in persistent infection and a protracted disease course [ 21 27 ]. Although controversial, many clinicians use Ct values as a proxy for viral load; generally, Ct values around 17–24 and around 40, which is closer to the limit of detection for most assays, are considered high and low viral loads, respectively [ 35 36 ].…”

“…Additional methodological details are provided in Figure 1 and in the Supplementary Methods and Supplementary Tables 1, 2 . This review included 19 studies that reported on a total of 24 patients (median age, 54.5 years [interquartile range (IQR) 44–64 years]; 15 male) [ 7 8 9 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 ].…”