Lahmer Tobias, Erber Johanna, Schmid Roland M, Schneider Jochen, Spinner Christoph D, Luppa Peter, Sörgel Fritz, Kinzig Martina, Rasch Sebastian
Department of Internal Medicine II, University hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich.
Institute of Clinical Chemistry and Pathobiochemistry, University hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich.
Multidiscip Respir Med. 2022 May 10;17:825. doi: 10.4081/mrm.2022.825. eCollection 2022 Jan 12.
The relationship between SARS-CoV-2 quantitative viral load and risk of disease progression, morbidity such as long- COVID or mortality in immunosuppressed, remains largely undefined in COVID-19 patients. Critically ill immunosuppressed patients potentially benefit from remdesivir treatment because of the prolonged course of their infection. Four critically ill immunocompromised patients and the impact of remdesivir on viral dynamics in lower respiratory samples were studied. Bronchoalveolar lavage (BAL) samples were assessed to measure SARS-CoV-2 quantitative viral load using real-time PCR. Corresponding plasma levels of remdesivir and its metabolite GS-441524 were determined. Mean virus load of 39.74 x 10 geq/ml (±33.25 x 10 geq/ml) on day 1 dropped significantly (p<0.008) to 3.54 x 10 geq/ml (±6.93 x 10 geq/ml) on day 3 and to 1.4 x 10 geq/ml (±2.35 x 10 geq/ml) on day 5 of remdesivir treatment. Mean virus load dropped below <1% between day 1 and 5 of remdesivir treatment. Parent prodrug remdesivir and also GS441524 metabolite levels of antiviral activity in our patients were far in excess of EC 50. Our data present that remdesivir treatment potentially reduces the SARS-CoV-2 viral load in immunosuppressed critically ill patients. However, the implication of viral load reduction on morbidity and mortality needs further investigation.
在新冠病毒感染患者中，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的定量病毒载量与疾病进展风险、诸如长期新冠等发病率或免疫抑制患者的死亡率之间的关系，在很大程度上仍不明确。由于感染病程延长，危重症免疫抑制患者可能从瑞德西韦治疗中获益。本研究观察了4例危重症免疫功能低下患者以及瑞德西韦对其下呼吸道样本中病毒动力学的影响。通过支气管肺泡灌洗（BAL）样本，采用实时聚合酶链反应（PCR）检测SARS-CoV-2定量病毒载量。测定了瑞德西韦及其代谢产物GS-441524的相应血浆水平。在瑞德西韦治疗第1天，平均病毒载量为39.74×10基因等效拷贝数/毫升（±33.25×10基因等效拷贝数/毫升），在第3天显著下降（p<0.008）至3.54×10基因等效拷贝数/毫升（±6.93×10基因等效拷贝数/毫升），在第5天降至1.4×10基因等效拷贝数/毫升（±2.35×10基因等效拷贝数/毫升）。在瑞德西韦治疗的第1天至第5天，平均病毒载量降至<1%。在我们的患者中，前体药物瑞德西韦及其代谢产物GS441524的抗病毒活性水平远超过半数有效浓度（EC50）。我们的数据表明，瑞德西韦治疗可能降低免疫抑制危重症患者的SARS-CoV-2病毒载量。然而，病毒载量降低对发病率和死亡率的影响仍需进一步研究。
