Early Remdesivir May Reduce Graft Loss in Kidney Transplant Recipients With COVID-19: Nitipong Permpalung, MD, MPH

Remdesivir (Veklury; Gilead Sciences) was shown to reduce the risk of all-cause graft loss and cardiovascular events in adult kidney transplant recipients with symptomatic COVID-19 who’d received at least 3 consecutive days of the antiviral therapy.¹

The recent study’s findings underscore the importance of evaluating antiviral treatments for underrepresented patients in COVID-19 clinical studies, such as kidney transplant recipients, Nitipong Permpalung, MD, MPH, a corresponding author and associate director of the Johns Hopkins Transplant Research Center, said in an interview with The American Journal of Managed Care^® (AJMC^®).

In this Q&A, Permpalung dissects the study’s findings and their implications for future clinical applications.

This transcript has been lightly edited for clarity.

AJMC: Kidney transplant recipients have often been underrepresented in pivotal COVID-19 antiviral trials. How does using a target trial emulation strengthen the evidence generated from this real-world cohort, and what are the limitations clinicians should keep in mind when interpreting these results?

Permpalung: Kidney transplant recipients were underrepresented in many of the original COVID-19 trials, so there is still an important gap in evidence for this population. At the same time, it would be difficult to justify a new randomized trial in which eligible high-risk patients are assigned to receive no antiviral treatment because current guidelines already recommend early antiviral therapy for these patients.

That's why carefully designed real-world studies are important. Target trial emulation is a way of using real-world data to recreate, as closely as possible, the ideal clinical trial. We define in advance who would be eligible, what counts as early remdesivir treatment, what the comparison group is, when follow-up begins, and which outcomes we want to measure.

This approach is more reliable than simply comparing patients who received treatment with those who did not because it helps reduce timing bias. To explain it more simply, patients needed to receive treatment for at least 3 days, so a simple analysis could make the treatment appear more beneficial simply because patients had to survive long enough to complete those 3 days. That's called immortal time bias.

However, it's important to recognize that this was an observational study. We found an association, but we cannot prove that remdesivir directly protected the kidney allograft or the cardiovascular system. In addition, the study compared remdesivir (Veklury; Gilead) with no antiviral treatment, so it does not tell us whether remdesivir is better than other antiviral treatment options.

AJMC: One of the more notable findings was the association between early remdesivir use and reduced cardiovascular events. What are the potential mechanisms behind this observation, and how might preventing severe COVID-19 translate into better long-term cardiovascular outcomes for transplant recipients?

Permpalung: I think the most likely explanation is not that remdesivir directly protects the heart but that early treatment may prevent COVID-19 from becoming more severe.

Severe COVID-19 can cause inflammation, blood clotting problems, low oxygen levels, and significant stress on the cardiovascular system. In one of our previous studies, we found that kidney transplant recipients with preexisting heart disease who were hospitalized for COVID-19 had the highest risk of later cardiovascular events. This suggests that patients who already have underlying heart disease may be particularly affected when COVID-19 becomes severe.

By treating the infection early and reducing its severity, remdesivir may reduce the risk of cardiovascular complications later on. This is a plausible explanation, but our study cannot prove that this is the exact pathway.

AJMC: Current CDC and Infectious Diseases Society of America guidelines recommend early antiviral therapy for patients at high risk of COVID-19 progression. Based on your findings, how should clinicians caring for kidney transplant recipients think about the timing of remdesivir initiation in routine practice?

Permpalung: For kidney transplant recipients, I think timing is very important. Antiviral treatment is most likely to help when it is started early.

Our findings support a simple approach in routine practice. When a kidney transplant recipient develops symptoms or tests positive for COVID-19, the patient should contact the transplant program promptly, and clinicians should assess antiviral treatment without waiting to see whether the patient becomes sicker.

If remdesivir is the most appropriate treatment option, it should be started as soon as it can be safely arranged. Current guidance recommends a 3-day course of treatment started within 7 days of symptom onset. Clinicians should think of those 7 days as the treatment window, not as a reason to wait until day 7.

It also means transplant programs need systems for rapid testing, treatment decisions, and access to outpatient infusions.

However, our study cannot tell us the exact best day to begin treatment, and it does not mean every kidney transplant recipient should receive remdesivir. The choice of antiviral therapy should still be individualized based on patient symptoms, drug interactions, safety considerations, preferences, and access to treatment. For example, some programs may not have outpatient infusion centers, so we cannot simply say that everyone should receive 3 days of intravenous remdesivir.

AJMC: The study was conducted across multiple pandemic waves, including the Omicron era, when disease severity was generally lower. How confident are you that these findings remain relevant to today's COVID-19 landscape?

Permpalung: I think the main message of our study remains relevant today, although the exact magnitude of benefit may be different.

Because our study included the Omicron era, it gives us greater confidence that the findings were not limited to the Delta or earlier waves, when COVID-19 was generally more severe. Kidney transplant recipients remain more vulnerable than the general population because they receive immunosuppressive therapy and often have other medical conditions.

Remdesivir targets the ribonucleic acid (RNA)-dependent RNA polymerase enzyme that the virus uses to replicate, rather than the spike protein, which changes more frequently between variants. Laboratory studies have shown that remdesivir remains active against recent variants, and current guidelines continue to recommend it as an early treatment option for appropriate high-risk patients.

At the same time, I recognize that the COVID-19 landscape has changed because of vaccination, previous infections, and generally lower disease severity. Patients today may have a lower risk of severe complications than during earlier waves. Overall, I think the message remains relevant, although the absolute benefit may be smaller in some populations.

AJMC: Your analysis suggests vaccination remains the frontline prevention strategy, with early antiviral therapy serving as a complementary approach. How should clinicians balance prevention and treatment strategies when caring for immunocompromised transplant recipients?

Permpalung: I think vaccination and antiviral treatment serve different purposes. They are 2 complementary layers of protection.

Vaccination remains an important first step because it reduces the risk of severe COVID-19 before infection occurs. However, kidney transplant recipients take immunosuppressive medications and may not develop the same level of protection from vaccination as the general population. Breakthrough infections can still occur despite vaccination, and those infections may still become severe.

Early antiviral treatment provides a second layer of protection after infection has already occurred. When a kidney transplant recipient develops COVID-19, clinicians should not assume vaccination alone provides enough protection, and they should not wait to see whether the illness becomes severe. Patients should be assessed promptly for antiviral treatment.

In practice, transplant programs should do both: help patients stay up to date with vaccination based on current recommendations and make sure patients know how to obtain testing and contact the transplant program quickly if they develop symptoms.

References

1. Srisurapanont K, Manothummetha K, Sirivakorn N, et al. Remdesivir and all-cause graft loss among kidney transplant recipients with symptomatic COVID-19. JAMA Netw Open. 2026;9;(7):e2625591. doi:10.1001/jamanetworkopen.2026.25591