Levels of metabolites were altered in long-COVID patients 2 years after infection, suggests a study published today in Scientific Reports.

Metabolites are products of metabolism, or the process of changing food and drink into energy, that have cell-level roles, such as providing fuel, structure, or defense.

Researchers at the Autonomous University of Zacatecas in Mexico led the study, which involved assessment of the plasma metabolome (set of metabolites) in 100 samples obtained from healthy controls, COVID-19 patients, and long-COVID patients in Mexico from 2020 and 2022.

The team measured concentrations of 108 metabolites using liquid chromatography and flow injection analysis with tandem mass spectrometry. They also asked participants to complete symptom questionnaires and used an immunoenzymatic assay to measure the levels of the protein interleukin 17 (IL-17) and the weight-maintenance hormone leptin in long-COVID patients.

All patients were fully vaccinated in 2021 and 2022. Six patients (12.5%) had mild COVID-19, 37 (77%) had moderate or severe infections, and 5 (10.4%) had critical cases.

Significant differences in 53 metabolites

A comparison of paired samples from 15 COVID-19 and long-COVID patients showed significant differences in 53 metabolites, with 13 upregulated and 32 downregulated in long-COVID patients.

Twenty-seven metabolites were still dysregulated in long-COVID patients compared with controls after 2 years. Long-COVID patients had different concentrations of lactic acid and arginine, altered lactate-pyruvate and ornithine-citrulline ratios, and significantly higher levels of IL-17.

The most common long-COVID symptoms included memory loss (73.3%); sleep disorders, joint pain, fatigue, exercise intolerance, and muscle pain (66.7%); and anxiety (60.0%).

Metabolomics ... has also proven to be a powerful tool for proposing and monitoring therapeutic interventions

"Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection," the study authors wrote.

They said metabolic information may partially explain the differences in disease presentation among long-COVID patients. "Metabolomics is not only useful in providing a snapshot of transient physiological or pathophysiological processes taking place in a living organism, but it has also proven to be a powerful tool for proposing and monitoring therapeutic interventions," they wrote.

A case-control study in Brazil during the Omicron wave of the pandemic reveals a two-dose COVID vaccine effectiveness (VE) of 49.4%, 26.0%, and 7.2% for children, adolescents, and young adults, respectively, but it was higher for certain vaccine types.

A three-dose VE against death was 64.5%. The study is published in JAMA Pediatrics and adds to the literature on the effectiveness of the booster doses of COVID-19 vaccines among children and adolescent recipients.

The test-negative case-control study was conducted between December of 2021 and August of 2022. The vaccines available to participants were BNT162b2 (Pfizer-BioNTech RNA vaccine), ChAdOx1 nCoV-19 (the AstraZeneca-Oxford vaccine), and CoronaVac (Sinovac's inactivated vaccine). A total of 2,080,867 children with a positive test result and 3,706,680 controls were included in the final analysis.

For children and adolescents, BNT162b2 had the highest VE(62.3%; (95% conference interval [CI], 60.7% to 63.9%) and 30.8% (95% CI, 28.9% to 32.6%), respectively. For young adults, ChAdOx1 nCoV-19 achieved the highest VE of 29.5%.

"Among adolescents and adults who received the booster dose, VE against symptomatic infection was similar for all vaccine types,” the authors said.

The booster dose was highly protective, however, against death. A third vaccine dose of any type resulted in a significant increase in VE against death for adolescents (80.8%) and young adults (61.7%).

VE against death was still effective after 2 doses for children and the booster dose for adolescents and young adults.

"Regardless of vaccine schedule, we observed low effectiveness in preventing Omicron infection in young people," the authors said. "However, VE against death was still effective after 2 doses for children and the booster dose for adolescents and young adults."

A survey of infection consultants in the United Kingdom found support for the "subscription-style" antibiotic payment model launched in England in 2022, researchers reported today in JAC-Antimicrobial Resistance.

The survey was designed to collect the views of National Health Service (NHS) infection consultants on the new antibiotic funding model, under which the NHS is paying annual fees of up to £10 million annually ($12.8 million US) for access to two antibiotics—ceftazidime/avibactam and cefiderocol—that will be prioritized for high-value clinical scenarios. The aim of the funding model is to delink the value of critical antibiotics from volume sold and stimulate the research and development of new antibiotics.

Low awareness but solid approval

Of the 753 infection consultants who received the surveys in November and December 2022, 235 (31.2%) responded. While only 58.3% of respondents (137 of 235) had heard of the payment model, 69.8% (164 of 235) agreed that it was a welcome development, 68.5% (161 of 235) said it would improve the ability of infection specialists to treat drug-resistant infections, and 57.9% (136 of 235) said it would stimulate the development of new antibiotics.

Under the new model, 42.1% (99/235) of consultants said they would use these antibiotics empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).

A 'subscription-type' model was viewed favourably and is likely to positively impact care.

When asked about use of the two antibiotics, respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC enzymes and cefiderocol for those producing beta-lactamase enzymes and infections caused by Stenotrophomonas maltophilia, Acinetobacter spp, and Burkholderia cepacia.

"In conclusion, among end-user infection consultants in England, a 'subscription-type' model was viewed favourably and is likely to positively impact care," the study authors wrote. "Delinked funding models are likely to affect the way physicians use antimicrobials, including indications and empirical use."

Emergent BioSolutions yesterday announced that it has received a 10-year contract worth up to $704 million from the Biomedical Advanced Research and Development Authority (BARDA) for advanced development and supply of a monoclonal antibody for treating Ebola virus infections. BARDA is part of the Administration for Strategic Preparedness and Response (ASPR) within the Department of Health and Human Services.

The monoclonal antibody is ansuvimab-zykl or mAb114 (Ebanga), which was approved by the Food and Drug Administration (FDA) in December 2020. The drug was formerly known as mAb114 and was developed by Ridgeback Biotherapeutics with support from BARDA. The two companies signed an agreement to allow Emergent to make and distribute the drug in the United States and Canada.  It is given as a single infusion.

Ebola virus has the ability to emerge unexpectedly, posing a risk to global health.

Under the terms of the agreement, Emergent will complete post-licensure agreements, including technology transfer for manufacturing scale-up, submission of a supplemental biologics licensing application to the FDA, and the completion of stability studies.

In a statement, Kelly Warfield, PhD, Emergent's senior vice president of science and development, said, "Ebola virus has the ability to emerge unexpectedly, posing a risk to global health. Its elusive nature makes it difficult to predict when and where an outbreak may occur, which underscores the importance of preparedness efforts against this public health threat."

• The US Department of Health and Human Services (HHS) yesterday announced the formation of the Office of Long COVID Research and Practice to manage the nation's response and coordinate clinical trials across federal departments, including the National Institutes of Health RECOVER (Researching COVID to Enhance Recovery) initiative. Yesterday, health officials detailed the plans for the initial phase of the long COVID research efforts, which will target virus persistence, neurologic symptoms, sleep problems, and autonomic symptoms.
• At the State Department, federal health officials today launched the new Bureau of Global Health Security and Diplomacy, which was announced in December 2022 to support President Biden's goal of prioritizing global health and positioning the State Department to advance US global health interests, which includes preventing, detecting, and responding to infectious disease outbreaks.
• In the latest H5N1 avian flu developments, the US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) reported another outbreak in poultry, which, like the most recent event, involves a live market housing 490 birds in New York's King County, which covers Brooklyn. And in overseas developments, the Netherlands' Wageningen University today said the BB genotype of the clade 2.3.4.4b H5N1 virus has been detected for the first time in poultry in the village of Biddinghuizen in Flevoland province, according to a statement flagged and posted by Avian Flu Diary (AFD), an infectious disease news blog. In Finland's fur farm outbreak developments, officials have ordered the culling of minks at affected farms. And in South Korea, as health officials probe H5N1 detections in cats at two Seoul animal shelters, media reports say H5 has been detected in cat food collected from one of the shelters, and a cat food maker has announced a recall of some of its products due to concerns about the supplier of raw poultry meat, according to reports translated and posted by AFD.