Cuesta Genoveva, Cacho Judit, Cucchiari David, Herrera Sabina, Sempere Abiu, Akter Tabassum, Villasante Anna, Garrido Miriam, Cofan Frederic, Diekmann Fritz, Soriano Alex, Marcos Maria Angeles, Bodro Marta
Department of Clinical Microbiology, Hospital Clínic of Barcelona, Carrer Villarroel, 170, 08036, Barcelona, Spain.
Department of Nephrology and Kidney, Transplantation Hospital Clinic, Barcelona, Spain.
Infect Dis Ther. 2024 Jul;13(7):1703-1713. doi: 10.1007/s40121-024-00991-6. Epub 2024 May 24.
There is no reliable microbiological marker to guide responses to antiviral treatment in kidney transplant recipients (KTR) with COVID-19. We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) RT-PCR before and after receiving treatment with remdesivir compared with genomic RNA (gRNA) RT-PCR and its use as a surrogate marker of viral replication.
We analyzed gRNA and sgRNA at baseline and after remdesivir treatment in KTR who received remdesivir for SARS-CoV-2 infection from November 2021 to February 2022.
Thirty-four KTR received remdesivir for SARS-CoV-2 infection. The median time since transplantation was 80 months (IQR 3-321) and 75% of patients had previously received 3 doses of a mRNA SARS-CoV-2 vaccine. Three patients (8%) were classified with mild, 25 (73%) with moderate, and 6 (17%) with severe SARS-CoV-2 infection. Thirty-two (94%) patients received 5 doses of remdesivir and two patients received 2 doses. The median time between symptom onset to remdesivir treatment was 5 days (IQR 3-8.5). The median days of hospitalization were 6 (IQR 2-112). gRNA was positive in all patients at baseline and after remdesivir. Five (15%) patients had negative sgRNA at baseline and 20 (59%) after receiving remdesivir. Patients presenting with negative sgRNA at baseline were discharged from hospital in ≤ 6 days without complications. Moreover, those with negative sgRNA after remdesivir therapy did not require ICU admission and had favorable outcomes. Nevertheless, patients with positive sgRNA after antiviral treatment presented worse outcomes, with 47% requiring ICU admission and the three (9%) recorded deaths in the study were in this group.
Based on these data, we hypothesize that sgRNA may have clinical utility to help monitor virologic response more accurately than gRNA in KTR who receive remdesivir. Moreover, patients with negative sgRNA at baseline may not require antiviral treatment and others presenting positive sgRNA at day 5 could benefit from prolonged or combined therapies.
对于感染新型冠状病毒肺炎（COVID-19）的肾移植受者（KTR），尚无可靠的微生物学标志物来指导抗病毒治疗反应。我们旨在评估与基因组RNA（gRNA）逆转录聚合酶链反应（RT-PCR）相比，接受瑞德西韦治疗前后亚基因组RNA（sgRNA）RT-PCR的动态变化及其作为病毒复制替代标志物的应用。
我们分析了2021年11月至2022年2月期间因严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染接受瑞德西韦治疗的KTR在基线和瑞德西韦治疗后的gRNA和sgRNA。
34例KTR因SARS-CoV-2感染接受了瑞德西韦治疗。移植后的中位时间为80个月（四分位间距3 - 321），75%的患者此前已接种3剂严重急性呼吸综合征冠状病毒2信使核糖核酸（mRNA）疫苗。3例（8%）患者被分类为轻症，25例（73%）为中症，6例（17%）为重症SARS-CoV-2感染。32例（94%）患者接受了5剂瑞德西韦，2例患者接受了2剂。症状出现至瑞德西韦治疗的中位时间为5天（四分位间距3 - 8.5）。住院的中位天数为6天（四分位间距2 - 112）。所有患者在基线和瑞德西韦治疗后gRNA均为阳性。5例（15%）患者在基线时sgRNA为阴性，20例（59%）患者在接受瑞德西韦治疗后sgRNA为阴性。基线时sgRNA为阴性的患者在≤6天内出院且无并发症。此外，瑞德西韦治疗后sgRNA为阴性的患者无需入住重症监护病房（ICU）且预后良好。然而，抗病毒治疗后sgRNA为阳性的患者预后较差，47%的患者需要入住ICU，研究中记录的3例（9%）死亡患者均在该组。
基于这些数据，我们推测在接受瑞德西韦治疗的KTR中，sgRNA可能比gRNA更具临床实用性，有助于更准确地监测病毒学反应。此外，基线时sgRNA为阴性的患者可能无需抗病毒治疗，而在第5天sgRNA为阳性的其他患者可能从延长治疗或联合治疗中获益。
