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. 2024 Jul;13(7):1703-1713.
doi: 10.1007/s40121-024-00991-6. Epub 2024 May 24.

Utility of SARS-CoV-2 Subgenomic RNA in Kidney Transplant Recipients Receiving Remdesivir

Genoveva Cuesta #  1 , Judit Cacho #  2 , David Cucchiari  2 , Sabina Herrera  3 , Abiu Sempere  3 , Tabassum Akter  1 , Anna Villasante  1 , Miriam Garrido  1 , Frederic Cofan  2 , Fritz Diekmann  2 , Alex Soriano  3   4   5 , Maria Angeles Marcos  6   7   8 , Marta Bodro  9   10   11
Affiliations

Utility of SARS-CoV-2 Subgenomic RNA in Kidney Transplant Recipients Receiving Remdesivir

Genoveva Cuesta et al. Infect Dis Ther. 2024 Jul.

Abstract

Introduction: 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.

Keywords: Dynamics of subgenomic RNA; Kidney transplant recipients; Monitor virological response; SARS-CoV-2.

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Conflict of interest statement

Alex Soriano is an Editor-in-Chief of Infectious Diseases and Therapy. Alex Soriano was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Marta Bodro has served on speakers’ bureaus for Gilead. Alex Soriano has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, Gilead, Menarini and Angelini, as well as grant support from Pfizer and Gilead. All other authors: none to declare.

Figures

Fig. 1
Fig. 1
Flowchart of outcomes according to sgRNA results
See this image and copyright information in PMC

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