SARS-CoV-2 mutation leads to resistance to remdesivir in 2 patients

A report published yesterday in Clinical Infectious Diseases describes a new SARS-CoV-2 mutation that confers resistance to the COVID-19 antiviral drug remdesivir in two persistently infected kidney transplant recipients treated with immunosuppressive drugs.

NYU researchers identified the V792I RNA-dependent 25 RNA polymerase mutation in the transplant patients, who were hospitalized and experienced life-threatening COVID-19 complications from reinfection after receiving remdesivir.

"Ineffective immune clearance contributes to persistent viral replication in immunocompromised hosts and increased opportunities for mutation," the researchers wrote. "The failure to appropriately identify, treat, and control the spread of mutated SARS-CoV-2 isolates could have far-reaching consequences."

One patient was in his or her 60s and had received two doses of the Pfizer/BioNTech COVID-19 vaccine before being infected with the Omicron subvariant BA.1.1 6 months after transplant and receiving a 5-day course of remdesivir. Twenty-four days later, the patient was readmitted to the hospital and given remdesivir. After 3.5 months, the patient was reinfected but had mild symptoms, so no treatment was given.

The other patient was in his or her 50s and had received two doses of the Moderna COVID-19 vaccine before becoming infected 14 months after transplant. The patient improved after receiving a 3-day course of remdesivir but was readmitted 18 days later because of worsening symptoms. After receiving a 5-day course of remdesivir, the patient improved.

Remdesivir is thought to work by disrupting SARS-CoV-2's ability to replicate. The authors noted that the drug is important for treating COVID-19 in transplant recipients because Paxlovid, another antiviral, can interfere with immunosuppressant drugs used to prevent organ rejection in these high-risk patients.

"Our results highlight the importance of continuing to monitor how the coronavirus changes over time and keeping on the lookout for genetic mutations that allow the virus to overcome the medical community's efforts to thwart it," senior author Adriana Heguy, PhD, said in an NYU news release. "In the future, physicians might also screen for such mutations before making treatment decisions for their most vulnerable patients."
Sep 26 Clin Infect Dis study
Sep 26 NYU
news release


Trial: Fecal microbiota transplantation superior to antibiotics for C difficile

A randomized clinical trial conducted in Denmark found that, in patients with a first or second Clostridioides difficile infection, fecal microbiota transplantation (FMT) was superior to standard-of-care antibiotic treatment in achieving sustained resolution of symptoms, researchers reported last week in The Lancet Gastroenterology & Hepatology.

Conducted at a university hospital in Aarhus, Denmark, the double-blind, placebo-controlled trial enrolled adult patients with a first or second C difficile infection and randomly assigned them to receive either FMT or placebo after receiving 10 days of vancomycin, the standard antibiotic treatment. Treatments were administered on day 1 and between days 3 and 7, and patients were followed for 8 weeks or until recurrence. The primary outcome was resolution of C difficile–associated diarrhea (CDAD) after 8 weeks.

A total of 42 patients were assigned to FMT (21) or placebo (21) from Jun 21, 2021, to Apr 1, 2022. Interim analysis on Apr 7 showed that 19 of 21 patients in the FMT group had resolution of CDAD at 8 weeks, compared with 7 of 21 in the placebo group, for an absolute risk reduction of 57%. Because of the significantly lower resolution rate in the placebo group, the trial was stopped for ethical reasons.

"In rare cases, it can happen that you discover that the treatment you are investigating is so effective that it is ethically indefensible to continue," first author Simon Mark Dahl Baunwall, MD, said in a press release from Aarhus University. "Our study is one example, in that the new FMT treatment is so much better than the standard treatment with antibiotics that it would be unethical to continue, because the patients in the control group would risk not receiving the FMT treatment."

Overall, 204 adverse events were reported, with one or more reported in 20 of 21 patients in the FMT group and all 21 in the placebo group. The most common adverse events were diarrhea and abdominal pain.
Sep 21 Lancet Gastroenterol Hepatol abstract
Sep 26 Aarhus University press release


DRC declares end of its 15th Ebola outbreak after single case

The Democratic Republic of the Congo (DRC) today declared that its latest Ebola flare-up is over, with the outbreak total remaining at one case, which involves a woman whose illness was genetically linked to a large outbreak in and around North Kivu province from 2018 through 2020.

The 46-year-old woman died in the middle of August at a hospital in Beni. She was initially treated for other conditions, but later showed symptoms consistent with Ebola.

In a statement, the World Health Organization (WHO) said the DRC's improvements in Ebola readiness and response have paid off. Health officials launched an Ebola vaccine campaign only a few days after the outbreak was declared, and more than 500 people were vaccinated, including healthcare workers. Nearly all of the 182 identified contacts were monitored for 21 days.

This was the DRC's 15th Ebola outbreak. It has had several small resurgences that were linked to persistent virus in survivors. Earlier this year, however, the country experienced an outbreak in Equateur province that was linked to a new jump from an animal source.

Today's announcement that the latest outbreak has ended comes as health officials gather for a meeting in Kinshasa to examine Ebola relapses and ways to support Ebola survivors. The virus is known to persist in immune-protected areas of the body.

Also, the end of the outbreak comes as health responders in Uganda battle an Ebola outbreak involving a different strain—Sudan—centered in communities near a busy road that leads to the DRC, an area near the North Kivu outbreak area. So far, 36 illnesses and 23 deaths have been reported in Uganda's outbreak.

Uganda's Health Minister Jane Ruth Aceng Ocero, MBChB, MPH, said today on Twitter than so far there are no confirmed cases in Kampala, the country's capital that is home to 1.5 million people. All samples from sick people in Kampala have been negative. She added that officials are awaiting test results on a sample from a person from Kasangati, which is just north of the city.
Sep 27 WHO statement on end of outbreak
Sep 27 WHO
statement on Ebola meeting
Sep 27 Aceng Ocero
Aug 22 CIDRAP News

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