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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：没有可靠的微生物学标志物来指导COVID-19肾移植受者（KTR）对抗病毒治疗的反应。我们旨在评估接受remdesivir治疗前后的亚基因组RNA（sgRNA）RT-PCR的动力学，与基因组RNA（gRNA）RT-PCR及其作为病毒复制替代标记的用途。
方法：我们分析了在2021年11月至2022年2月因SARS-CoV-2感染而接受雷德西韦治疗的KTR中基线和雷德西韦治疗后的gRNA和sgRNA。
结果：34名KTR因SARS-CoV-2感染接受了remdesivir。移植后的中位时间为80个月（IQR3-321），75％的患者先前接受过3剂SARS-CoV-2mRNA疫苗。三名患者（8％）被归类为轻度，25（73％）与中度，严重SARS-CoV-2感染6例（17%）。32例（94％）患者接受了5剂remdesivir，2例患者接受了2剂。症状发作与雷米西韦治疗之间的中位时间为5天（IQR3-8.5）。中位住院天数为6天（IQR2-112）。gRNA在所有患者基线和remdesivir后均为阳性.5名（15％）患者在基线和20（59％）接受remdesivir后，sgRNA阴性。基线时sgRNA阴性的患者在≤6天内出院，无并发症。此外，那些在接受remdesivir治疗后sgRNA阴性的患者不需要入住ICU,并且结局良好.然而，抗病毒治疗后sgRNA阳性的患者预后较差，47%的患者需要入住ICU,3例(9%)的死亡病例均在本组.
结论：根据这些数据，我们假设在接受remdesivir的KTR中,sgRNA可能比gRNA更准确地监测病毒学应答具有临床应用价值.此外，基线时sgRNA阴性的患者可能不需要抗病毒治疗,其他在第5天出现sgRNA阳性的患者可从延长治疗或联合治疗中获益.
方法：我们分析了在2021年11月至2022年2月因SARS-CoV-2感染而接受雷德西韦治疗的KTR中基线和雷德西韦治疗后的gRNA和sgRNA。
结果：34名KTR因SARS-CoV-2感染接受了remdesivir。移植后的中位时间为80个月（IQR3-321），75％的患者先前接受过3剂SARS-CoV-2mRNA疫苗。三名患者（8％）被归类为轻度，25（73％）与中度，严重SARS-CoV-2感染6例（17%）。32例（94％）患者接受了5剂remdesivir，2例患者接受了2剂。症状发作与雷米西韦治疗之间的中位时间为5天（IQR3-8.5）。中位住院天数为6天（IQR2-112）。gRNA在所有患者基线和remdesivir后均为阳性.5名（15％）患者在基线和20（59％）接受remdesivir后，sgRNA阴性。基线时sgRNA阴性的患者在≤6天内出院，无并发症。此外，那些在接受remdesivir治疗后sgRNA阴性的患者不需要入住ICU,并且结局良好.然而，抗病毒治疗后sgRNA阳性的患者预后较差，47%的患者需要入住ICU,3例(9%)的死亡病例均在本组.
结论：根据这些数据，我们假设在接受remdesivir的KTR中,sgRNA可能比gRNA更准确地监测病毒学应答具有临床应用价值.此外，基线时sgRNA阴性的患者可能不需要抗病毒治疗,其他在第5天出现sgRNA阳性的患者可从延长治疗或联合治疗中获益.
