Monoclonal Antibody Shows Promise Against RSV in Infants, Influenza Vaccine Updated, Metformin May Reduce Long COVID Risk, and More
Monoclonal Antibody Treatment Show Promise for Preventing RSV Infections in Infants1
The monoclonal antibody (mAb) clesrovimab has demonstrated significant promise in preventing respiratory syncytial virus (RSV) infections in infants, with potential availability by 2025. In clinical trials presented at IDWeek, clesrovimab was found to be 91% effective at preventing severe medically attended lower respiratory tract infections compared with placebo, and a single dose was shown to be as effective as five doses of the existing RSV treatment, palivizumab, in high-risk infants.
The research involved two studies assessing clesrovimab's safety and efficacy among healthy infants and those at risk for severe RSV. Octavio Ramilo, MD, chair of infectious diseases at St. Jude’s Children’s Research Hospital, highlighted that clesrovimab targets a different site on the RSV F protein than nirsevimab, allowing it to protect against both RSV subtypes A and B.
In a phase 2b/3 trial with 2,411 infants, clesrovimab showed 81.3% efficacy at preventing hospitalizations and 91.7% efficacy at preventing severe infections over 6 months. In another phase 3 trial comparing clesrovimab to palivizumab, the incidence of severe infections was similar between the groups, but clesrovimab required only one dose versus five for palivizumab.
Adverse events were comparable between both treatments, with no causal relationship to the deaths reported in either group. Given the high-risk nature of the participants, the trial is extending into a second RSV season to assess ongoing safety and efficacy.
Next steps include investigating the long-term benefits of RSV prevention in infants and evaluating the safety of clesrovimab in immunocompromised children. Dr. Ramilo expressed particular interest in this population due to the high incidence of severe RSV disease in children undergoing cancer treatment or with other immunodeficiencies.
Influenza Vaccine Updated to Drop Influenza B/Yamagata Strain Due to Lack of Cases2
This year's influenza vaccine will not include the Influenza B/Yamagata strain, which has not been reported since spring 2020. The FDA determined that this strain poses minimal risk to human health, primarily because of COVID-19 measures like social distancing and masking that effectively eliminated its circulation. Rebecca Wurtz, MD, MPH, an infectious disease physician and epidemiologist at the University of Minnesota School of Public Health, noted this as a unique case of a virus potentially going extinct due to human behavior.
Kawsar Talaat, MD, an infectious disease physician at Johns Hopkins Bloomberg School of Public Health, explained that pre-existing immunity against B/Yamagata contributed to its disappearance, contrasting with the novel SARS-CoV-2 virus, which could not be contained in the same way. The absence of B/Yamagata will not significantly affect the influenza vaccination process, as other strains like B/Victoria and various influenza A lineages continue to circulate.
The decision to simplify the vaccine to a trivalent formulation, protecting against three viruses instead of four, allows for increased production efficiency. Kevin R. McCarthy, PhD, an assistant professor at the University of Pittsburgh's Center for Vaccine Research, agreed that including a strain with no current threat is not beneficial, and eliminating it from the vaccine minimizes risks related to manufacturing exposure to the virus.
Metformin Reduces Risk of Long COVID and Death Following SARS-CoV-2 Infection3
A study presented at IDWeek 2024 found that metformin prescribed within a week of SARS-CoV-2 infection was associated with a 53% reduction in the incidence of long COVID or death among individuals without diabetes or prediabetes. Most participants were infected with the Omicron variant.
Led by Carolyn Bramante, MD, MPH, an internist, pediatrician, and obesity medicine specialist at the University of Minnesota Medical School, researchers utilized the National COVID Cohort Collaborative (N3C) Electronic Health Record Database to simulate a randomized controlled trial. Participants received metformin within 6 days of infection, while a control group was prescribed off-label medications like fluvoxamine and ivermectin, which have not shown efficacy in treating acute COVID-19 outcomes.
The study demonstrated that 4.0% of individuals in the metformin group developed long COVID or died within 6 months, compared with 8.5% in the control group, resulting in a relative risk of 0.47. The strongest protective effect was noted when metformin was administered within the first 2 days of infection, showing a relative risk of 0.39.
Emily Erbelding, MD, MPH, director of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, highlighted the significance of these findings, emphasizing the lack of effective therapies for long COVID. Given metformin's established safety and low cost, the study suggests it may be a potential treatment option. However, the authors acknowledged limitations related to variability in defining long COVID and the influences on prescribing decisions. Overall, the study calls for further research to validate these promising results.
Wastewater Monitoring Detects Early Signs of Avian Influenza4
Researchers reported at IDWeek 2024 that a biomarker for avian influenza A (H5N1) was identified in Texas wastewater treatment plants more than a month before the first confirmed cases of H5N1 in dairy cattle were reported in 2024. This retrospective finding highlights the effectiveness of wastewater monitoring in early detection of potential outbreaks, enabling timely public health responses.
The H5N1 outbreak, primarily affecting poultry in the United States, has raised concerns due to its recent spread to cattle and a limited number of human cases. As of October 11, 2024, the CDC documented 20 human cases of H5N1 since April, with one prior case in 2022.
The research team, led by Alessandro Zulli, PhD, a postdoctoral fellow at Stanford University, utilized wastewater monitoring to investigate unusual spikes in influenza A virus levels in Texas during early 2024. Historically used to track various pathogens, including cholera and polio, wastewater-based epidemiology has recently gained attention for monitoring COVID-19 and other viruses.
The Stanford WastewaterSCAN team, in collaboration with Emory University and Verily, monitors more than190 wastewater locations nationally, assessing more than a dozen pathogens three times a week. Their analysis indicated rising H5N1 levels in poultry, mammals, and wild birds, prompting an investigation into the influenza uptick in Texas.
The researchers developed a digital droplet H5 reverse transcription polymerase chain reaction assay to detect the H5 hemagglutinin gene associated with avian flu, achieving 100% specificity and 90% sensitivity. During the monitoring period, 59 wastewater plants exhibited increased H5 gene concentrations, aligning with the emergence of H5N1 in dairy cattle. A plant in Amarillo, Texas detected H5N1 on February 24, 2024, 2 weeks prior to reported illnesses in cattle.
Dr. Zulli emphasized that early detection provides critical time for public health officials to mobilize resources, test farms, and monitor medical facilities for potential human cases linked to cattle exposure. He noted that wastewater monitoring represents a rapid and unbiased approach to measuring pathogen prevalence, with broad implications for managing emerging infectious diseases.
References:
- Kellner S. Merck’s RSV shot for infants shows promise, could be available in 2025. Healio. October 23, 2024. Accessed November 5, 2024. https://www.healio.com/news/pediatrics/20241023/mercks-rsv-shot-for-infants-shows-promise-could-be-available-in-2025
- Boden S. The flu shot is different this year, thanks to COVID. NPR. October 17, 2024. Accessed November 5, 2024. https://www.npr.org/sections/shots-health-news/2024/10/17/nx-s1-5155104/flu-shot-vaccine-b-yamagata-extinct
- Frellick M. Metformin may reduce long COVID in non-diabetic population. Medscape. October 22, 2024. Accessed November 5, 2024. https://www.medscape.com/viewarticle/metformin-may-reduce-long-covid-non-diabetic-population-2024a1000ja0
- Frellick M. Wastewater acts as an early warning system for bird flu outbreaks. Medscape. October 21, 2024. Accessed November 5, 2024. https://www.medscape.com/viewarticle/wastewater-acts-early-warning-system-bird-flu-outbreaks-2024a1000j69