Extensive SARS-CoV-2 evolution in a 613-day infected immunocompromised patient

Persistent SARS-CoV-2 infection in immunocompromised patients provides an optimal environment for accelerated viral evolution. We present a 72-year-old male patient with a history of allogeneic stem cell transplantation as treatment for a myelodysplastic and myeloproliferative (MDS/MPN) overlap syndrome, complicated by the development of a posttransplant diffuse large B-cell lymphoma for which he received multiple immunosuppressive agents, including rituximab. He was diagnosed with a SARS-CoV-2 BA.1 infection and subsequently treated with sotrovimab, sarilumab, and dexamethasone. Throughout the infection course, 32 nasopharyngeal samples were collected, with consistent SARS-CoV-2 positivity and fluctuating viral loads (median Ct value 26.0 [range 15.9-32.0]). Whole-genome sequencing of 25 samples revealed extensive viral evolution with over 50 mutations, particularly in the spike protein region. The patient experienced recurrent respiratory symptoms, and ultimately died 613 days after the first positive SARS-CoV-2 RT-PCR result due to relapse of the MDS/MPN overlap syndrome. This case underscores the importance of sequential sampling and sequencing, given the potential public health threat of introducing viral escape variants into the community.