Is there evidence supporting the use of remdesivir for longer than 10 days in the treatment of COVID-19?

Introduction
COVID-19 disease, caused by the spread of SARS-CoV-2 virus via respiratory droplets, emerged in 2019 and has since led to significant global morbidity and mortality.1,2 As of 2024, millions of confirmed cases and deaths have been reported worldwide.3 While the virus affects individuals of all ages, older adults and those with comorbidities or compromised immune systems face a higher risk of severe disease.1,2 Despite the success of vaccination efforts in reducing severe disease and hospitalization rates, disparities in access and outcomes persist, particularly in vulnerable populations (immunocompromised, etc).

The severity classification for COVID-19 disease is divided into 3 categories based on clinical presentation and oxygen requirements.1,2 Mild-to-moderate disease is characterized by an SpO2 ≥94% on room air, with no need for supplemental oxygen, but with risk factors for severe disease.1 The Centers for Disease Control and Prevention (CDC) maintain an up-to-date list of demographic risk factors and underlying medical conditions associated with a higher risk of experiencing severe outcomes of COVID-19.4 Age is the most significant risk factor, particularly those aged ≥50 years and especially those aged ≥65 years. Severe disease is classified as an SpO2 of <94% on room air or need for supplemental low-flow oxygen. Critical disease, the most severe form of COVID-19, requires advanced respiratory support such as high-flow oxygen, mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO). These classifications help guide treatment decisions and resource allocations.

Remdesivir
Remdesivir, a SARS-CoV-2 nucleotide analog RNA polymerase inhibitor, is Food and Drug Administration (FDA) approved for treating COVID-19 in adults and pediatric patients (≥1.5 kg) who are either hospitalized or nonhospitalized but have mild-to-moderate disease and are at high risk for progression to severe COVID-19.5 The drug is administered as a once daily intravenous infusion, with the approved treatment regimen varying based on disease severity and treatment setting. For nonhospitalized patients, a 3-day course initiated within 7 days of symptom onset is recommended. In hospitalized patients not requiring MV/ECMO, a 5-day course is standard, extendable to 10 days if clinically warranted. For critically ill patients requiring MV/ECMO, a 10-day course is recommended.

Guideline recommendations
Clinical guidelines for COVID-19 management largely align with product labeling while emphasizing specific patient contexts.1,2 Both an Infectious Diseases Society of America (IDSA) guideline (updated August 12, 2024) and a National Institutes of Health (NIH) guideline (final update February 29, 2024) highlight the importance of individualized treatment durations for remdesivir, particularly for severely immunocompromised patients. The NIH guideline specifically notes that longer or additional courses of remdesivir may be appropriate for these patients if they show limited clinical improvement or evidence of ongoing viral replication.2

Available recommendations reflect the unique challenges faced by severely immunocompromised individuals, whose weakened immune systems often fail to control viral replication, resulting in delayed recovery and increased complications.2 While guidelines stress tailoring treatment durations for this population to address their heightened risks and potential for viral evolution, the safety and e fficacy of remdesivir use beyond 10 days remains unclear.1,2

Literature review
Four observational studies have reported on the use of remdesivir therapy beyond 10 days for the treatment of COVID-19 (Table 1).6-9 Most investigations focus on immunocompromised patients with persistent COVID-19 infections, with only 1 investigation confirmed to take place during the Omicron era.

Gras et al (2024) conducted a retrospective cohort study involving 18 high-risk hematological patients with COVID-19 treated during the Omicron era.6 Patients received extended remdesivir therapy (median duration, 19 days; IQR, 16.8 to 25.0), guided by polymerase chain reaction cycle thresholds (which indicate the presence of the viral genetic material) and clinical presentation. Additional therapies, including convalescent plasma and nirmatrelvir/ritonavir, were administered as needed. The study reported a median remdesivir treatment duration of 3.5 weeks, determined by viral clearance time, with no adverse events or readmissions observed. Martinez et al (2024) also reported on an immunocompromised patient who achieved complete viral clearance after 30 days of remdesivir therapy.7 Additional case reports reporting remdesivir treatment durations of 12 and 18 days are also available.10,11

In a physician-based survey by Brown et al (2022), the clinical features and treatment responses of 31 immunocompromised patients with chronic (lasting >21 days) or relapsing (>2 episodes) COVID-19 were examined.8 Two of 3 patients who received remdesivir treatment for 11 to 20 days achieved viral clearance.

Lastly, remdesivir resistance was explored by Santos-Bravo et al (2022) in a prospective cohort study of hospitalized patients with COVID-19.9 A total of 38 patients received remdesivir therapy for >5 days (median, 10; IQR, 7 to 21); 21 of these patients were classified as remdesivir non-responders based on the presence of SARS-CoV-2 subgenomic RNA at the end of 5 or more days of therapy. Authors did not report the number of patients who received more than 10 days of treatment. However, they concluded that remdesivir treatment duration is not a risk factor for developing remdesivir resistance mutations.

Table 1. Outcomes with remdesivir treatment >10 days in patients with COVID-19 illness.6-9
Gras et al (2024)6Brown et al (2022)8Bravo et al (2022)9Martinez et al (2022)7
Study designRetrospective cohortPhysician-based surveyProspective cohortCase report
PopulationN=18 high-risk hematological patients with COVID-19N=31 immunocompromised patients with chronic/relapsing COVID-19 with positive SARS-CoV-2 PCR for ≥48 days and median symptomatic disease duration for 62 daysN=149
hospitalized patients with COVID-19, including non-responders to RDV		A 44-year-old immunocompromised patient with COVID-19 illness and positive SARS-CoV-2 PCR for 5 months
Circulating COVID-19 variant at time of studyOmicronUnknown; likely pre-OmicronPredominantly DeltaUnknown; likely pre-Omicron
Prolonged RDV useN=18 patients received RDV as part of a combination therapy for 16 to 25 daysN=3 patients received RDV monotherapy for 11 to 20 daysN=38 received RDV >5 days (median, 10; IQR, 7 to 21)N=1 patient received RDV until 2 negative NP SARS-CoV-2 PCR tests were received 24 hours apart
COVID-19 outcomes with prolonged RDVViral clearance was achieved in a median of 3.5 weeks with no additional treatment, readmissions, deaths, or long-term COVID-19 sequelae reported during follow-up2 of 3 patients achieved viral clearance21 patients receiving RDV >5 days were classified as RDV non-responders based on persistent viral replication.

RDV treatment duration was not a risk factor for developing RDV resistance mutations.		Complete viral eradication after 30 days of RDV.

Symptom free at 12 months of follow up.

Minor hair thinning reported during follow up that reversed.
Abbreviations: IQR, interquartile range; NP, nasopharyngeal; PCR, polymerase chain reaction, RDV, remdesivir.

Conclusion
Limited data from small observational studies suggest that remdesivir treatment beyond 10 days may be effective for patients with persistent COVID-19 illness, particularly immunocompromised individuals. However, guidelines for the treatment of COVID-19 state that significant knowledge gaps remain regarding the treatment of immunocompromised patients and the use of prolonged remdesivir courses. This underscores the need for personalized treatment plans, close monitoring, and further studies to establish the efficacy, safety, and optimal duration of remdesivir therapy for immunocompromised and other vulnerable populations.

References 

  1. Guidelines on the Treatment and Management of Patients with COVID-19. Infectious Diseases Society of America. Updated August 12, 2024. Accessed December 20, 2024. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
  2. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Updated February 29, 2024. Accessed December 20, 2024. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines
  3. COVID Data Tracker. Updated December 17, 2024. Accessed December 20, 2024. CDC COVID Data Tracker: Home.
  4. Centers for Disease Control and Prevention. Underlying conditions and the higher risk for severe COVID-19. Updated July 30, 2024. Accessed December 20, 2024. https://www.cdc.gov/covid/hcp/clinical-care/underlying-conditions.html
  5. Veklury. Package Insert. Gilead Sciences; 2020. Accessed December 20, 2024.
  6. Gras E, Aiello TF, Chumbita M, et al. Extended remdesivir administration in haematological patients with malignancies and COVID-19 during the Omicron era: safety and outcomes. J Antimicrob Chemother. 2024;79(9):2364-2368. doi:10.1093/jac/dkae237
  7. Martinez MA, Chen TY, Choi H, et al. Extended remdesivir infusion for persistent Coronavirus Disease 2019 infection. Open Forum Infect Dis. 2022;9(8):ofac382. doi:10.1093/ofid/ofac382
  8. Brown LK, Moran E, Goodman A, et al. Treatment of chronic or relapsing COVID-19 in immunodeficiency. J Allergy Clin Immunol. 2022;149(2):557-561.e1. doi:10.1016/j.jaci.2021.10.031
  9. Santos Bravo M, Alonso R, Soria D, et al. Genetic Study of SARS-CoV-2 Non structural protein 12 in COVID-19 patients non responders to remdesivir. Microbiol Spectr. 2022;10(6):e0244822. doi:10.1128/spectrum.02448-22
  10. Bermingham WH, Canning B, Wilton T, et al. Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection. Front Immunol. 2023;14:1135834. doi:10.3389/fimmu.2023.1135834
  11. Ambati S, Ali B, Seddon O, et al. Resolution of persistent SARS-CoV-2 infection with prolonged intravenous remdesivir and vaccination in a patient post CAR-T. Int J Hematol. 2023;117(5):765-768. doi:10.1007/s12185-022-03518-2

Prepared by:

Karol Marcela Suarez
PharmD Candidate Class of 2025

Katherine Sarna, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy
February 2025

The information presented is current as November 13, 2024. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.