Today in the New England Journal of Medicine Chinese researchers have published positive trial results of simnotrelvir, an oral antiviral that can shorten the duration of mild to moderate COVID-19 symptoms.

Unlike with Paxlovid or other antivirals tested against the virus, the simnotrelvir trial was conducted on mostly healthy young adults, none of whom had severe symptoms. The study included 1,208 patients enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir, and 605 to receive placebo. The study ran from August to December 2022.

The formulation used in the study included ritonavir added to simnotrelvir, which acted as a booster to the antiviral. The average age of study participants was 35, and approximately 50% had a comorbidity such as obesity.

Symptoms reduced by 1.5 days

Among patients who began treatment within 72 hours of symptom onset, the length of COVID-19 symptoms was on average 36 hours shorter in the simnotrelvir group (180.1 hours; 95% confidence interval [CI], 162.1 to 201.6] than in the control group (216.0 hours; 95% CI, 203.4 to 228).

Viral loads were also significantly lower among the treatment group by day 5, dropping 30-fold more than loads seen in the control group.

Simnotrelvir was associated with an additional decrease in viral load until day 9.

"Simnotrelvir had more benefits for the alleviation of respiratory symptoms than placebo. In addition, simnotrelvir was associated with an additional decrease in viral load until day 9," the authors wrote.

The researchers noted a higher incidence of adverse events during treatment in the simnotrelvir group than in the placebo group (29.0% vs 21.6%), but most adverse events were mild or moderate. Notably, the treatment group had an increase in blood triglyceride levels, a phenomenon seen with the use of other antivirals.

No study participants died.

The results of a randomized clinical trial show that early switch to oral antibiotic therapy was non-inferior to continuing intravenous (IV) therapy in patients with low-risk Staphylococcus aureus bloodstream infection, researchers reported yesterday in The Lancet Infectious Diseases.

The trial, conducted at 31 hospitals in Germany, France, the Netherlands, and Spain, involved 213 patients (mean age, 63.5 years, 69% male) with low-risk S aureus bloodstream infection who were randomized 1:1 after 5 to 7 days of IV antibiotic therapy to switch to oral therapy or continue with IV therapy, with a total antibiotic duration of 14 days. The composite primary end point was the occurrence of any complication related to S aureus bloodstream infection within 90 days in the intention-to-treat population. The non-inferiority margin was 10%.

In the group that switched to oral antibiotics, 14 (13%) of 108 participants met the primary end point, compared with 13 (12%) of 105 in the IV group, with a treatment difference of 0.7 percentage points (95% confidence interval, –7.8 to 9.1), which met the non-inferiority criteria. In addition, hospital stays were shorter in the oral-switch group, with a median of 12 days versus 16 days for patients who remained on IV therapy.

In the oral-switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event, compared with 27 (26%) of 103 participants in the IV group.

Simplifying treatment

While guidelines recommend at least 14 days of IV antibiotics for patients with low-risk S aureus bloodstream infection, the investigators say the results of the trial support an early switch to oral therapy for such patients, "provided a rigorous clinical assessment and close monitoring for complications are done."

"With these findings, it is possible to simplify treatment and to discharge patients more quickly," lead investigator Achim Kaasch, MD, head of the Institute for Medical Microbiology and Hospital Hygiene at the Otto von Guericke University of Magdeburg, Germany, said in a press release.

CARB-X announced today that it is awarding $1.7 million to St. Paul, Minnesota—based biotechnology company Syntiron to develop a maternal vaccine that targets two leading causes of neonatal sepsis.

The money will support early-stage development of Syntiron's Alloy-EK vaccine, which targets iron receptor proteins in Escherichia coli and Klebsiella pneumoniae, the bacteria that cause a large portion of neonatal sepsis infections. A recent study estimates that sepsis—an overwhelming reaction to infection that can lead to organ failure and death—killed 2.5 million children under the age of 5 in 2017, mostly in low- and middle-income countries.

Because newborns are too young to be immunized, the vaccine would be given to expectant mothers, who are also at risk of urinary tract infections caused by these pathogens and can pass them on to newborns during childbirth. The hope is that vaccinated mothers would pass the antibodies on in utero and through breast milk and strengthen their newborns' immune system against infection.

Targeting a 'tremendous burden'

"The bacteria targeted by this vaccine are a tremendous burden on public health for babies, children, and adults worldwide," Syntiron Managing Director Lisa Herron-Olson, PhD, said in a CARB-X press release. "Preventing these infections by vaccination offers substantial potential health benefit to mothers and babies, while reducing the spread of antimicrobial resistance."

Syntiron's vaccine candidate is the most recent of the 94 early-stage projects designed to prevent, treat, and diagnose antibiotic-resistant infections that have been supported by CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) since it was founded in 2016.

Three of 135 patients in a Brazilian cohort were reinfected with the Zika virus (ZIKV), according to a study published yesterday in Emerging Infectious Diseases.

A team led by Brazilian researchers sequenced 238 ZIKV genomes obtained from 135 adults who gave plasma, urine, or semen samples over 1 year to assess viral persistence. Participants were recruited within 1 week of Zika symptom onset from June 2017 to June 2019. The average patient age was 38 years.

ZIKV is transmitted in tropical and subtropical regions through the bite of Aedes mosquitoes. While 80% of Zika cases cause few or no symptoms, infected pregnant women can give birth to babies with severe birth defects, including microcephaly, an abnormally small head. After a large Zika outbreak occurred in Brazil in 2015, viral circulation declined, and cases are uncommon today.

Frequency of reinfection remains unknown

The viral genomes clustered with previously reported ZIKV strains from northern Brazil, and evidence suggested that the virus has mutated little over time and that within-host diversity was limited in most Zika-persistent samples.

But atypical virus temporal diversity was detected in samples from more than five participants, revealing divergent genomes in the same patients. These patients had elevated levels of neutralizing antibody levels, which fell off during recovery from infection only to rise again in three patients 6 months after the initial infection.

We underscore the necessity of implementing continuous surveillance strategies, which are vital for monitoring the evolutionary changes of viruses over time and gaining a comprehensive understanding of arbovirus diversity.

The three patients, who reported no symptoms, also tested positive for Zika on real-time reverse transcription polymerase chain reaction (RT-PCR), confirming reinfection.

Because Zika often does not require medical care, many reinfections may have gone unnoticed, the study authors said. "Our findings hold significant implications for public health, epidemiology, clinical practice, and diagnostics," they wrote. "However, the frequency of reinfections during the latest ZIKV outbreaks remains uncertain." 

"We underscore the necessity of implementing continuous surveillance strategies, which are vital for monitoring the evolutionary changes of viruses over time and gaining a comprehensive understanding of arbovirus diversity," the researchers added.