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

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.