Coronavirus disease 2019 (COVID-19) infection results in both acute mortality and persistent and/or recurrent disease in patients with hematologic malignancies, but the drivers of persistent infection in this population are unknown. We found that B-cell lymphomas were at particularly high risk for persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. Further analysis of these patients identified discrete risk factors for initial disease severity compared with disease chronicity. Active therapy and diminished T-cell counts were drivers of acute mortality in COVID-19–infected patients with lymphoma. Conversely, B cell–depleting therapy was the primary driver of rehospitalization 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. Significance: We describe the largest cohort of persistent symptomatic COVID-19 infection 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. This article is highlighted in the In This Issue feature, [p. 1][1] [1]: /lookup/volpage/12/1?iss=1

中文翻译：

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淋巴恶性肿瘤患者长期感染 SARS-CoV-2

2019 年冠状病毒病 (COVID-19) 感染会导致血液系统恶性肿瘤患者急性死亡以及持续和/或复发性疾病，但该人群持续感染的驱动因素尚不清楚。我们发现 B 细胞淋巴瘤持续严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 阳性的风险特别高。与疾病慢性期相比，对这些患者的进一步分析确定了初始疾病严重程度的离散风险因素。积极治疗和 T 细胞计数减少是 COVID-19 感染淋巴瘤患者急性死亡率的驱动因素。相反，B 细胞消耗疗法是 COVID-19 再住院的主要驱动因素。在 SARS-CoV-2 持续阳性的患者中，我们观察到与宿主内病毒进化一致的高水平病毒熵，特别是在 CD8+ T 细胞免疫受损的患者中。这些结果表明，持续性 COVID-19 感染可能仍然是适应性免疫受损患者的风险，需要额外的治疗策略来清除这一高危人群中的病毒。意义：我们描述了淋巴恶性肿瘤患者持续有症状的 COVID-19 感染的最大队列，并将 B 细胞耗竭确定为持续感染的关键免疫驱动因素。此外，我们证明了持续感染 COVID-19 的患者，特别是 CD8+ T 细胞免疫受损的患者，正在发生宿主内病毒进化。本文在 In This Issue 功能中突出显示，[p. 1][1] [1]：