SARS-CoV-2 viral load dynamics in immunocompromised critically ill patients on remdesivir treatment

IF 2 Q3 RESPIRATORY SYSTEM Multidisciplinary Respiratory Medicine Pub Date : 2022-01-12 DOI:10.4081/mrm.2022.825
T. Lahmer, J. Erber, R. Schmid, J. Schneider, C. Spinner, P. Luppa, F. Sörgel, M. Kinzig, S. Rasch
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引用次数: 2

Abstract

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 107 geq/ml (±33.25 x 107 geq/ml) on day 1 dropped significantly (p<0.008) to 3.54 x 106 geq/ml (±6.93 x 106 geq/ml) on day 3 and to 1.4 x 105 geq/ml (±2.35 x 105 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.
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免疫功能低下危重患者接受瑞德西韦治疗后的SARS-CoV-2病毒载量动态
在新冠肺炎患者中,SARS-CoV-2定量病毒载量与疾病进展风险、长期COVID等发病率或免疫抑制患者死亡率之间的关系在很大程度上仍不明确。危重免疫抑制患者可能受益于瑞德西韦治疗,因为他们的感染过程延长。研究了四名免疫功能受损的危重患者以及瑞德西韦对下呼吸道样本中病毒动力学的影响。评估支气管肺泡灌洗(BAL)样本,以使用实时PCR测量严重急性呼吸系统综合征冠状病毒2型的定量病毒载量。测定了瑞德西韦及其代谢产物GS-441524的相应血浆水平。瑞德西韦治疗第1天的平均病毒载量39.74 x 107 geq/ml(±33.25 x 107 geq/ml)显著下降(p<0.008),第3天降至3.54 x 106 geq/ml(±6.93 x 106 geq/ml),第5天降至1.4 x 105 geq/ml。瑞德西韦治疗的第1天至第5天,平均病毒载量降至<1%以下。我们患者的母体前药瑞德西韦和GS441524代谢产物的抗病毒活性水平远远超过EC50。我们的数据表明,瑞德西韦治疗可能降低免疫抑制危重患者的严重急性呼吸系统综合征冠状病毒2型病毒载量。然而,病毒载量减少对发病率和死亡率的影响需要进一步研究。
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来源期刊
CiteScore
4.40
自引率
0.00%
发文量
23
审稿时长
>12 weeks
期刊介绍: Multidisciplinary Respiratory Medicine is the official journal of the Italian Respiratory Society - Società Italiana di Pneumologia (IRS/SIP). The journal publishes on all aspects of respiratory medicine and related fields, with a particular focus on interdisciplinary and translational research. The interdisciplinary nature of the journal provides a unique opportunity for researchers, clinicians and healthcare professionals across specialties to collaborate and exchange information. The journal provides a high visibility platform for the publication and dissemination of top quality original scientific articles, reviews and important position papers documenting clinical and experimental advances.
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