- Kidney transplant recipients face severe COVID-19 risks but often are excluded from key antiviral trials.
- In a target trial emulation, starting remdesivir (Veklury) soon after a COVID diagnosis was associated with a 47% lower risk of graft failure or death at 1 year.
- Early remdesivir also was associated with a 42% lower risk of cardiovascular events.
Kidney transplant recipients with COVID-19 who received remdesivir (Veklury) early had a lower risk of graft loss, a target trial emulation study found.
Compared with no remdesivir, initiation of the antiviral within 7 days of a COVID diagnosis was associated with a 47% lower risk of graft failure or death at 1 year in an analysis that employed clone-censor-weight adjustment (HR 0.53, 95% CI 0.31-0.92), reported Nitipong Permpalung, MD, MPH, of Johns Hopkins University School of Medicine in Baltimore, and colleagues.
This association was generally consistent across clinically relevant subgroups, according to the findings in JAMA Network Open, and early remdesivir was also associated with a 42% lower risk of cardiovascular events (HR 0.58, 95% CI 0.35-0.98).
“The main message for clinicians is to act early,” Permpalung told MedPage Today. “When a kidney transplant recipient develops COVID-19 symptoms or tests positive, the patient should contact the transplant team promptly, and antiviral treatment should be considered before the illness becomes severe.”
Remdesivir is an important option particularly when an oral antiviral is not clinically suitable, he added. “However, our findings do not mean that every kidney transplant recipient should automatically receive remdesivir,” Permpalung cautioned. “Treatment should be individualized based on the timing of infection, the patient’s clinical risk, drug interactions, safety, preferences, and access to treatment.”
Kidney transplant recipients have a high risk of severe COVID-19 due to chronic immunosuppression, impaired vaccine responses, and comorbidities. “Mortality in hospitalized kidney transplant recipients during the early pandemic ranged from 20% to 32%, declining to 1% to 4% during the Omicron wave, likely due to vaccination, prior infection, and improved treatment,” the researchers wrote.
“Prevention and treatment should be viewed as complementary,” Permpalung emphasized. “Vaccination remains the first layer of protection, but kidney transplant recipients may still have breakthrough infections because of their immunosuppression. When infection occurs, there should already be a plan for rapid testing, contacting the transplant team, and accessing antiviral treatment.”
Although CDC guidelines recommend early antiviral therapy for patients at high risk of COVID-19 progression, many supporting trials excluded patients with severe kidney impairment and transplant recipients.
“Previous clinical trials showed that early antiviral treatment can reduce severe COVID-19 in high-risk patients,” said Permpalung. “However, kidney transplant recipients were underrepresented in many of those trials, and most studies focused on short-term outcomes such as hospitalization or death.”
Remdesivir use in kidney transplant recipients also has raised concerns about nephrotoxic effects and drug-drug interactions with immunosuppressive agents like tacrolimus.
To address these research gaps, the team emulated a target trial using retrospective observational data from five hospitals in the Johns Hopkins Health System. The analysis included 432 kidney transplant recipients with symptomatic COVID-19 from March 2020 through January 2024, all of whom had a functioning allograft. Of those, 41% initiated early remdesivir within 7 days of diagnosis and received at least 3 consecutive days of therapy while the rest received no remdesivir.
The median age was 57 years and 57.4% of patients were male. Most infections occurred during the Omicron wave (60.2%), with the remainder distributed across the pre-Delta (33.6%) and Delta (6.2%) periods. Those who received anti-SARS-CoV-2 monoclonal antibodies, nirmatrelvir-ritonavir (Paxlovid), or molnupiravir (Lagevrio) were excluded.
Prior to weighting, patients who received early remdesivir were generally older, more frequently required supplemental oxygen, and were more likely to be vaccinated. In the weighted analysis, early initiation of remdesivir was not tied to a lower-risk of all-cause mortality on its own (HR 0.51, 95% CI 0.24-1.06) or long COVID (HR 0.65, 95% CI 0.21-2.05).
The study compared early remdesivir with no antiviral treatment and findings should not be interpreted as showing that remdesivir is better than other antiviral options, Permpalung said. The long COVID outcome was limited by few events.
“Future research should compare active treatments directly and identify which transplant recipients are most likely to benefit from each approach,” he stated.
