Prolonged SARS-CoV-2 infection in patients with lymphoid malignancies

Abstract

ABSTRACT Coronavirus disease 2019 (COVID-19) infection results in high mortality rates in patients with hematologic malignancies. Persistent and/or recurrent COVID-19 has not yet been demonstrated in this population. We identified patients with B-cell lymphomas as having a particularly high risk for persistent SARS-CoV-2 positivity. Subsequent analysis of patients with lymphoid malignancies and COVID-19 identified discrete risk factors for severity of primary infection as compared to disease chronicity. Active therapy and diminished T-cell counts were key drivers of acute mortality in lymphoma patients with COVID-19 infection. Conversely, B-cell depleting therapy was the primary driver of re-hospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population. Statement of Significance We establish persistent symptomatic COVID-19 infection as a novel clinical syndrome in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.