Abstract
Hematologic malignancies and chemotherapy are risk factors for COVID-19 progression and mortality. Immunocompromised hosts, particularly those with severe B-cell depletion, can shed viable viruses for extended periods, which can lead to persistent infection. We present the case of a 73-year-old male with diffuse large B-cell lymphoma (stage IV-B) under curative immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). After the first episode of mild COVID-19, he developed two severe relapses following the third and fourth cycles of R-CHOP. Lung CT scans performed in both episodes showed new-onset ground-glass infiltrates and fibrosis of previously affected pulmonary segments. In light of similar semiquantitative SARS-CoV-2 viral loads between episodes, without further risk exposure or microbiological findings, persistent COVID-19 with severe clinical relapses was assumed and successfully treated with polyclonal immunoglobulin and remdesivir. Whole-genome sequencing was performed in all samples, confirming the same specimen, which belonged to the B.1.177 lineage. This case stands out for the unusually long viral persistence and the various relapses of severe COVID-19 related to the worsening immune status with each immunochemotherapy cycle.