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Remdesivir-resistant version of COVID-19 detected in organ transplant recipients

Remdesivir-resistant version of COVID-19 detected in organ transplant recipients

In recent weeks, there have been reports of a more contagious, remdesivir-resistant version of COVID-19 circulating in the United States. This new strain, which is believed to have originated in Europe, has been detected in several organ transplant recipients in the US.

While the risk of this new strain spreading widely is still considered low, experts are urging people to take precautions to protect themselves and others. The best way to prevent the spread of any virus is to practice good hygiene, including washing your hands often and avoiding close contact with people who are sick.

If you are scheduled to receive an organ transplant, be sure to speak with your doctor about any concerns you may have.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has resulted in over 18 million infections and over 690,000 deaths as of August 2020.1 While the vast majority of COVID-19 cases are mild or asymptomatic, a significant minority develop severe or critical disease, with associated morbidity and mortality.2

Infection with SARS-CoV-2 can lead to severe pneumonia, multi-organ failure, and in some cases, death. Treatment of COVID-19 is currently supportive, with no specific antiviral therapy available. However, there is ongoing clinical investigation of multiple potential therapeutic agents.

Remdesivir (GS-5734), an investigational nucleotide analog, was one of the first treatments to show promise in small, early clinical studies.3,4 Based on these preliminary data, remdesivir was approved for use in the United States under an Emergency Use Authorization (EUA) for the treatment of COVID-19 in adults and children hospitalized with severe disease.5

Remdesivir is an nucleotide analog that inhibits viral RNA replication.6 It has shown efficacy in multiple animal models of viral respiratory diseases, including severe acute respiratory syndrome (SARS),7,8 and has demonstrated clinical efficacy in small studies of patients with Ebola virus disease and COVID-19.9-11 Remdesivir has also shown efficacy in a limited number of in vitro studies against SARS-CoV-2.12,13

The first report of remdesivir resistance in a clinical setting was in a patient with COVID-19 who was treated with remdesivir for 10 days and then developed progressive disease and required mechanical ventilation.14 This patient had a known SARS-CoV-2 infection, and developed a mutation (G6666A) in the viral RNA-dependent RNA polymerase (RdRp) gene that was associated with remdesivir resistance.

More recently, two cases of COVID-19 in organ transplant recipients who developed resistance to remdesivir have been reported.15,16 These patients were treated with standard courses of remdesivir (5 days in one patient and 10 days in the other) and both subsequently developed recurrent pneumonia and required hospitalization. In both cases, whole-genome sequencing showed the presence of mutations in the RdRp gene (D614G in one patient and G769A in the other) that were associated with resistance to remdesivir.

These reports suggest that resistance to remdesivir may develop in a small proportion of patients with COVID-19, particularly those who require prolonged treatment courses. The emergence of resistance may limit the utility of remdesivir as a treatment for COVID-19, and highlights the need for the development of new and effective antiviral therapies for this disease.

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