Adults with kidney transplants who were treated for COVID-19 with the antiviral remdesivir within a week of COVID-19 diagnosis and who received at least three consecutive days of therapy were less likely than kidney transplant recipients who did not receive the antiviral to experience cardiovascular or kidney problems up to a year later, according to findings from a target trial emulation study that published July 28 in JAMA Network Open.

“These findings suggest that timely antiviral treatment may have benefits beyond the acute phase of COVID-19 in this population,” says Nitipong Permpalung, M.D., M.P.H., senior study author and associate director of the Johns Hopkins Transplant Research Center. “We hope these findings will help reduce hesitations that physicians may have with considering providing remdesivir, when clinically appropriate, to adult kidney transplant recipients.”

Permpalung explains that physicians consider many factors when it comes to treating COVID-19 for kidney transplant recipients. This includes assessing their immune function and kidney health, the use of immune-suppressing therapies, drug interactions, treatment side effects and the timing and severity of COVID-19. The short-term benefits of antivirals for patients with increased risk factors for severe outcomes have been established, but this study is one of the largest to provide data, including long-term outcomes, for adult kidney transplant recipients. These are patients who often aren’t included in randomized trials due to underlying risks.

To assess long-term outcomes, the investigators identified adult kidney transplant recipients who were diagnosed with COVID-19 between March 2020 and January 2024 and received care at one of five Johns Hopkins Medicine hospitals in Maryland. Among 432 adult kidney transplant recipients, 177 (41%) received at least a three-day course of remdesivir within a week of a COVID-19 diagnosis, and 255 (59%) did not receive remdesivir. Those who received other COVID-19 therapies, including monoclonal antibodies and other antivirals, were excluded from the analysis.

The patients selected for this simulated trial were divided into two groups: those who received remdesivir, which was provided intravenously, and those who did not. All patients were followed for up to a year. The main outcome assessed was all-cause graft loss, defined as graft failure (rejection of the kidney transplant) or death from any cause. Secondary outcomes included cardiovascular complications, death from any cause, and long COVID.

Among the 432 adults, 48 (11%) experienced all-cause graft loss. Forty-three (10%) experienced a cardiovascular complication, such as a heart attack, stroke or cardiac-related death. Death from any cause occurred in 35 patients (8%). Seventeen patients (4%) had long COVID.

After accounting for several variables among participants, including differences in age, underlying health conditions, medications, disease severity, when they received a transplant, and if they had a COVID-19 vaccine and when they were diagnosed with COVID-19, the investigators found that early remdesivir treatment was associated with a 47% lower risk of all-cause graft loss and a 42% lower risk of cardiovascular events compared to no remdesivir. Trends but no significant associations were found for a reduced risk of death from any cause. The analysis for long COVID was inconclusive because few patients had documented long COVID.

Overall, many participants had underlying risk factors for or experienced moderate to severe COVID-19 outcomes. Eighty-eight of the adults (20%) required supplemental oxygen at diagnosis. Additionally, 413 (95%) had high blood pressure, 199 (46%) had diabetes and 63 (15%) had coronary artery disease.

Approximately 109 (25%) participants had a kidney transplant within a year before they had COVID-19. More than half, 254 (59%), stopped taking an immunosuppressive drug needed to prevent the body from rejecting the transplant at the time of their COVID diagnosis.

Most participants, 260 (60%), had COVID-19 when the omicron strains of SARS-CoV-2, the virus that causes COVID-19, were circulating after Dec. 15, 2021. One-third, 145 (34%), had COVID-19 during the pre-delta wave (up until July 1, 2021). Others, 27 (6%), had COVID-19 during the delta period (July 2–Dec. 15, 2021).

More than half of the study participants also received a COVID-19 vaccine. This included 165 (38%) who received three or more doses and 89 (21%) who received one to two. Patients who received remdesivir were older (median age of 61 compared to 54 in the non-remdesivir group) and more likely to require breathing assistance (33% vs. 11%).

“Several biologically plausible mechanisms may explain the observed associations,” says Karan Srisurapanont, M.D., the first study author. “Early suppression of viral replication may reduce systemic inflammation, endothelial injury, or damage to blood vessels, and thrombotic complications, or those related to severe blood clotting, that may contribute to heart and kidney problems.”Additional authors include Kasama Manothummetha, Nirada Siriyakorn, Mary Bowring, Lucy Li, Willa Cochran, Cory Schulz, Sean Ellis, Kanin Thammavaranucupt, Daniel Brennan, Robin Avery and William Werbel.

This study did not receive specific funding. Some authors reported unrelated or investigator-level grant support and disclosures as listed below.

Grants from NIH were noted for Mary Bowring (F30HL16882, T32GM136577), Lucy Li (K08AI193077) and William Werbel (K23AI157893, R01AI190359). Robin Avery has received funding from Aicuris, Astra-Zeneca, Merck, Takeda and United Therapeutics. Nitipong Permpalung consults for Basilea, Pulmocide Ltd. and ClearView HealthCare Partners, and has received research grants from CareDx, IMMY Diagnostics, Applied BioCode, Pearl Diagnostics, Scanogen, Fujifilm and Merck.