Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding was observed from the upper respiratory tract of a female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Shedding of infectious SARS-CoV-2 was observed up to 70 days, and of genomic and subgenomic RNA up to 105 days, after initial diagnosis. The infection was not cleared after the first treatment with convalescent plasma, suggesting a limited effect on SARS-CoV-2 in the upper respiratory tract of this individual. Several weeks after a second convalescent plasma transfusion, SARS-CoV-2 RNA was no longer detected. We observed marked within-host genomic evolution of SARS-CoV-2 with continuous turnover of dominant viral variants. However, replication kinetics in Vero E6 cells and primary human alveolar epithelial tissues were not affected. Our data indicate that certain immunocompromised individuals may shed infectious virus longer than previously recognized. Detection of subgenomic RNA is recommended in persistently SARS-CoV-2-positive individuals as a proxy for shedding of infectious virus.

在患有慢性淋巴细胞白血病和获得性低丙种球蛋白血症的女性免疫功能低下个体的上呼吸道中观察到长期严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 脱落。初步诊断后，可在长达 70 天的时间内观察到传染性 SARS-CoV-2 的脱落，在长达 105 天的时间内观察到基因组和亚基因组 RNA 的脱落。首次使用恢复期血浆治疗后，感染并未被清除，这表明对该个体上呼吸道中的 SARS-CoV-2 的作用有限。第二次恢复期血浆输注几周后，不再检测到 SARS-CoV-2 RNA。我们观察到 SARS-CoV-2 显着的宿主内基因组进化，以及主要病毒变异体的不断更新。然而，Vero E6 细胞和原代人肺泡上皮组织中的复制动力学并未受到影响。我们的数据表明，某些免疫功能低下的个体传播传染性病毒的时间可能比之前认识的要长。建议在 SARS-CoV-2 持续阳性个体中检测亚基因组 RNA，作为传染性病毒脱落的指标。