New study shows metformin given during acute COVID-19 infection reduced risk of clinician-diagnosed long COVID by 50%

University of Minnesota Medical School

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MINNEAPOLIS/ST. PAUL (6/11/2026) — New findings from the ACTIV-6 randomized clinical trial provide important confirmation of prior clinical trial results that metformin, a widely available and inexpensive medication with an established safety record, reduced the risk of clinician-diagnosed long COVID when started during acute COVID-19 infection.

The study, published in Clinical Infectious Diseases and co-led by a University of Minnesota Medical School research team, evaluated nearly 3,000 outpatient adults with mild-to-moderate COVID-19 across 90 sites in the United States. Participants were randomized to receive either metformin or placebo within seven days of symptom onset and were followed for six months.

At six months, participants who received metformin experienced a 50% relative reduction in the risk of clinician-diagnosed long COVID compared with those receiving placebo, indicating that metformin cut the risk of a medical diagnosis of long COVID by approximately half.

Among participants followed through 180 days, clinician-diagnosed long COVID occurred in 0.56% of those receiving metformin compared with 1.17% of those receiving placebo.

"This trial provides additional evidence that treating acute infection with this intervention that acts on metabolic health can reduce the likelihood of developing long COVID," said Carolyn Bramante, MD, MPH, assistant professor at the University of Minnesota Medical School, internist and pediatrician with M Health Fairview and lead author of the study. "The finding is particularly important because metformin is inexpensive, globally available and has decades of clinical use supporting its safety."

As a National Center for Advancing Translational Sciences (NCATS)-funded CTSI Scholar, Dr. Bramante developed a program to study metformin as an outpatient treatment for acute SARS-CoV-2 because of its history as an anti-viral in the early 1900s and because of its known anti-inflammatory actions.

The ACTIV-6 trial enrolled adults considered to be low, standard, or high risk between September 2023 and May 2024 during a period when most participants already had substantial immunity from prior vaccination, prior infection or both. More than 83% of participants had evidence of prior partial immunity, making the results highly relevant to the current phase of the pandemic.

While the trial's primary endpoint — responding yes to having any COVID-19 symptoms on Day 180 after starting the trial — did not meet the pre-specified threshold for efficacy, metformin consistently favored improved long-term outcomes. Investigators observed a high probability of benefit for reducing symptom burden and preventing clinician-diagnosed long COVID. Additionally, no safety concerns emerged during the study.

The findings replicate results from the earlier University of Minnesota-led COVID-OUT randomized trial, which reported a similar reduction in long COVID among participants treated with metformin during acute infection. 

“Reproducing research is very important, and both trials have also been replicated in analyses of electronic health record data. Together, these independent studies support that in low- to high-risk adults, metformin is an effective strategy to reduce the risk of long COVID,” said David Boulware, MD, MPH, professor at the University of Minnesota Medical School, infectious disease physician with M Health Fairview and steering committee co-chair of the trial.  

Next steps in this research include looking at biospecimens taken during acute infections and seeing if similar actions exist during other infections. 

This research was funded by NCATS.

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About the University of Minnesota Medical School
The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. Learn more at med.umn.edu.

About ACTIV-6

ACTIV-6 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) is a nationwide, randomized, placebo-controlled platform trial designed to evaluate repurposed medications for the treatment of COVID-19. The study was supported by the National Center for Advancing Translational Sciences (NCATS).

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Journal

Clinical Infectious Diseases

DOI

10.1093/cid/ciag335 

Method of Research

Randomized controlled/clinical trial

Subject of Research

People

Article Title

Metformin on the Presence of COVID-19 Symptoms 6 Months after Infection: The ACTIV-6 Randomized Clinical Trial

Article Publication Date

4-Jun-2026

COI Statement

Bramante: Reports grants from the NIH outside the current work during the conduct of the study. Stewart: Reports grants from NIH NCATS during the conduct of the study; Grants from NIH outside the submitted work. Boulware: Reports grants from NIH during the conduct of the study. McCarthy: Nothing to report. Gao: Nothing to report. Rothman: Reports grants from NIH, PCORI, AHRQ, CDC, CardioHealth Alliance during the conduct of the study. Spouse owns stock in Moderna unrelated to the current work. Mourad: Nothing to report. Thicklin: Nothing to report. Cohen: Nothing to report. Garcia del Sol: Nothing to report. Shah: Nothing to report. Mehta: Nothing to report. Cardona: Nothing to report. Scott: Nothing to report. Ginde: Reports grants from NIH during the conduct of the study; Grants from NIH, CDC, DoD, AbbVie (investigator-initiated), and Faron Pharmaceuticals (investigator-initiated) outside the submitted work. Castro: Reports institutional grant funding from NIH, ALA, PCORI, AstraZeneca, GSK, Novartis, Pulmatrix, Sanofi-Aventis, Shionogi; Speaker/Consultant fees from Grant Funding, Genentech, Teva, Sanofi-Aventis; Consultant fees from Merck, Novartis, Arrowhead, OM Pharma, Allakos; Speaker honorarium from Amgen, AstraZeneca, GSK, Regeneron; Royalties from Elsevier all outside the submitted work. Jayaweera: Reports grants from NCATS during the study; Grants from Gilead, Pfizer, Janssen, and ViiV. advisory board fees from ViiV and Theratechnologies outside the submitted work. Sulkowski: Reports advisory board fees from AbbVie, Gilead, GSK, Atea, Antios, Precision Bio, Viiv, and Virion; Institutional grants from Janssen outside the submitted work. Gentile: Reports personal fees from Duke University for protocol development and oversight during the conduct of the study; grants from NIH outside the submitted work. McTigue: Reports grants from NIH to the University of Pittsburgh during the conduct of the study; Research contracts to the University of Pittsburgh from Pfizer, Eli Lilly, and Janssen outside the submitted work. Felker: Reports institutional research grants from NIH during the conduct of the study and from Novartis outside the submitted work. Collins: Reports grant funding from NHLBI and personal fees from Vir Biotechnology during the conduct of the study. Dunsmore: Nothing to report. Adam: Reports other from US Government Funding through Operation Warp Speed during the conduct of the study. Lindsell: Reports institutional grants from NCATS during the conduct of the study; Institutional grants from NIH, CDC, and DoD; Contract with institution for research services from Endpoint Health, bioMerieux, Entegrion Inc, Abbvie, and Astra Zeneca, Biomeme, and Novartis outside the submitted work; Dr Lindsell has a patent for risk stratification in sepsis and septic shock issued to Cincinnati Children's Hospital Medical Center. Hernandez: Reports grants from American Regent, Amgen, Boehringer Ingelheim, Merck, Verily, Somologic, and Pfizer; Personal fees from AstraZeneca, Boston Scientific, Cytokinetics, Bristol Myers Squibb, and Merck outside the submitted work. Naggie: Reports grants from NIH, the sponsor for this study, during the conduct of the study; Institutional research grants from Gilead Sciences, AbbVie; Consulting fees from Pardes Biosciences; Scientific advisor/Stock options from Vir Biotechnology; Consulting with no financial payment from Silverback Therapeutics; DSMB fees from Personal Health Insights, Inc; Event adjudication committee fees from BMS/PRA outside the submitted work

 

New framework aims to transform high-altitude medicine through whole-body approach to hypoxia

Compuscript Ltd

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Figure 1. Conceptual framework of Hypoxia Stress-induced Multi-organ Injury (HSMI).

 

 

 

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Credit: STTT

https://doi.org/10.1038/s41392-026-02836-9

 

As increasing numbers of people live, work, and travel at high altitudes, experts are calling for a major shift in how altitude-related health conditions are understood, diagnosed, and treated. A new perspective published in Signal Transduction and Targeted Therapy highlights the growing burden of illnesses linked to low-oxygen environments and introduces a comprehensive framework designed to advance the future of high-altitude medicine.

 

High-altitude regions, generally defined as areas above 2,500 metres, are home to millions of permanent residents and attract large numbers of visitors each year. Exposure to reduced oxygen levels can affect multiple organs and contribute to a wide range of conditions, including acute mountain sickness, pulmonary complications, cardiovascular disorders, metabolic disturbances, and long-term organ damage. Despite decades of progress in understanding individual altitude illnesses, many conditions continue to be viewed and managed separately.

 

The article proposes a new model known as Hypoxia Stress-induced Multi-organ Injury (HSMI), which views altitude-related illnesses as interconnected manifestations of a common underlying process. Rather than focusing on isolated organs, the framework emphasizes how oxygen deprivation triggers widespread biological responses that can affect the lungs, brain, heart, liver, kidneys, and gastrointestinal system over time.

 

“For decades, altitude-related illnesses have been treated as separate problems” said Prof. Fengming Luo, corresponding author of the study at West China Hospital, Sichuan University. “HSMI shows they are interconnected responses to oxygen deprivation. That changes how we think about early diagnosis and prevention.” This integrated perspective could help overcome longstanding challenges in the field. Current diagnostic approaches often rely heavily on symptoms rather than objective biological indicators, making early detection difficult. The article highlights the need for real-time diagnostics, advanced biomarkers, portable imaging technologies, and continuous physiological monitoring capable of identifying health risks before severe symptoms develop.

 

The proposed roadmap also focuses on understanding why individuals respond differently to altitude exposure. Factors such as genetics, age, sex, and population-specific adaptations may influence vulnerability to hypoxia. Incorporating multi-omics technologies, artificial intelligence, and predictive modelling could enable more personalized risk assessment and prevention strategies for people ascending to or residing at high altitude.

 

In addition, the article outlines opportunities for developing precision therapeutics that target the biological mechanisms driving altitude-related illness. Such approaches could move beyond symptom management and support interventions aimed at preventing or reducing long-term organ damage associated with chronic hypoxia.

 

As global engagement with high-altitude environments continues to expand, the HSMI framework offers a new vision for prevention, diagnosis, and treatment, providing a foundation for more coordinated and effective healthcare strategies in some of the world’s most challenging environments.

  

Figure 2. Future directions for advancing high-altitude medicine based on the HSMI framework.

Credit

STTT

Article Reference

Wenjin Sun, Xuan Zhang, Ling Chen, Lei Chen, Cheng Deng, Shizheng Wu, Fengming Luo, Advancing high-altitude medicine: a model for the future, Signal Transduction and Targeted Therapy, https://doi.org/10.1038/s41392-026-02836-9

Keywords

High-Altitude Medicine, Hypoxia Stress-Induced Multi-Organ Injury (HSMI), Hypoxia, Precision Medicine, Altitude-Related Diseases

 

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Journal

Signal Transduction and Targeted Therapy

DOI

10.1038/s41392-026-02836-9 

 

Leaf traits drive herbivory across forests: Silicon and heat tolerance matter

South China Botanical Garden, Chinese Academy of Sciences

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The paper quantified leaf herbivory in 61 woody species across five Chinese forests, and disentangled the effects of leaf functional traits, insect richness, and climate on insect feeding. Leaf functional traits were the dominant drivers of herbivory. Leaf silicon concentration served as a key anti-herbivore trait, while high heat tolerance increased plant susceptibility to insects. Herbivory intensified in hot, wet regions with rich insect richness. Evergreen plants experienced heavier leaf damage than deciduous plants. This study advances our understanding of plant-insect interactions across forest ecosystems.

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Credit: Longxin Lu, Yangsiding Wang, Muhammad Waseem, Ruifang Jiao, Qiurui Ning, Han Chen, Yi Li, Xiaojuan Liu, Pengcheng He, Huizhong Fan, Qing Ye, and Hui Liu.

Date: June 11, 2026

Guangzhou, China: Scientists have long struggled to explain why some plant species sustain more leaf damage than others. It has long been assumed that species adopting a resource-acquisitive strategy suffer more from leaf herbivory, and that those adapted to resource-rich environments face greater herbivory pressure.

However, empirical evidence testing these assumptions simultaneously across large-scale environmental gradients has been lacking. The researchers surveyed leaf herbivory levels, 11 leaf functional traits, insect richness and climatic factors across 61 woody species in five distinct forest sites across China.

“The herbivory patterns were far from what we expected. Species with tougher leaves actually suffered more herbivory,” said first author Longxin Lu from SCBG. “This suggests an ongoing arms race between plants and insects, in which insects have evolved stronger mandibles to overcome such mechanical defenses.”

In contrast, plants with higher leaf silicon concentrations sustained significantly less damage. Silicon-based defense appears to function independently of the leaf carbon economics spectrum.

“Surprisingly, species with higher heat tolerance experienced greater herbivory,” said corresponding author Dr. Hui Liu. “Vigorous, high-performing plants are more attractive to herbivores.”

At the environmental scale, plants growing in hotter, wetter forests with higher insect richness endured more herbivory. Nevertheless, when all factors were analyzed collectively, leaf functional traits explained variations in herbivory better than environmental factors.

As global temperatures rise and precipitation patterns shift, understanding the drivers of leaf herbivory is critical for predicting forest health. The researchers note that traditional frameworks for plant defense should be expanded to incorporate silicon-based defensive strategies and abiotic stress tolerance traits.

“Integrating multiple intrinsic and extrinsic drivers is essential,” added Dr. Hui Liu. “Our study provides a framework for predicting herbivory under future climate scenarios.”

This study, published in the journal Plant Diversity (IF=6.3, https://doi.org/10.1016/j.pld.2026.04.005), was supported by the National Natural Science Foundation of China and other funding bodies.

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Journal

Plant Diversity

DOI

10.1016/j.pld.2026.04.005 

Method of Research

Experimental study

Subject of Research

Not applicable

Article Title

Disentangling intrinsic and extrinsic drivers of herbivory across forests: Leaf functional traits, insect richness, and climatic factors

COI Statement

Declaration of competing interest: The author Hui Liu is an Editorial Board Member for Plant Diversity and was not involved in the editorial review or the decision to publish this article.The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

 

New study explores potential cross-species spread of chronic wasting disease

A serious wildlife disease is prompting growing concern among scientists, conservationists and public health experts

University of Calgary

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A deer without any symptoms of CWD.

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Credit: Dr. Hermann Schaetzl

Chronic wasting disease (CWD) is generally associated with animals. But a new study by researchers from the University of Calgary and international collaborators explored the potential for CWD to spread from deer, elk and other cervid (hooved, plant-eating) animals to other species.

There has never been a confirmed case of CWD in humans. However, researchers say the findings reinforce the need for continued surveillance and research as the disease expands geographically.

Caused by infectious proteins known as prions, CWD, a fatal neurological illness, continues to spread across North America, including growing regions of Alberta.

In a newly published study in Science Advances, researchers from the University of Calgary and collaborators around the world explored the zoonotic potential of CWD in controlled laboratory settings. While most animals remained asymptomatic, researchers detected low levels of prions in their tissues and transferred samples to other species that developed symptoms of CWD.

“These findings show that even without obvious (clinical signs), infectious prions can still be present and transmissible,” says Dr. Samia Hannaoui, PhD, researcher and assistant professor at the University of Calgary Faculty of Veterinary Medicine  (UCVM), and first author on the study.

An evolving and unpredictable disease

Prions are unusual infectious agents because they can change and adapt as they move between hosts, potentially giving rise to new strains with different biological properties.

“We’re not dealing with a single, fixed agent,” says Dr. Hermann Schaetzl, MD, Dr. med, UCVM professor and last author on the study. “Prion strains can evolve, and that evolution can influence how the disease behaves.”

Researchers say this variability makes prion diseases especially difficult to predict and control.

CWD also spreads in ways that make containment challenging. Infected animals can carry and shed infectious prions into the environment for months or even years before showing symptoms, contaminating soil and vegetation through urine and feces.

“By the time you see clinical signs, the animal has often been infectious for a long time,” says Schaetzl. “That’s what makes this disease particularly challenging to control.”

What researchers know and what remains uncertain

“Our findings don’t indicate an immediate risk to humans, but they do suggest the situation is more nuanced than previously understood,” says Schaetzl. “As CWD becomes more widespread, understanding these dynamics becomes increasingly important.”

Researchers note that prion diseases have crossed species barriers before. The best-known example is bovine spongiform encephalopathy (BSE), or “mad cow disease,” which was transmitted from cattle to humans.

While current evidence suggests the barrier between CWD and humans is strong, experimental studies like this continue to explore whether prions could adapt over time in ways that alter transmission potential and disease manifestation.

Why spread matters

Although the risk to humans is considered low, researchers say increasing prevalence in wildlife raises the importance of ongoing monitoring and mitigation efforts.

“The more the disease spreads in animals, the more opportunities there are for exposure,” says Schaetzl. “Risk is linked to prevalence.”

Researchers at UCalgary are also investigating ways to slow transmission in cervid populations. Recent vaccine studies in mouse models designed to mimic infection in deer and elk showed promising early results, with vaccinated animals shedding fewer infectious prions during early and late stages of disease and surviving longer after exposure. 

“If we can reduce shedding, we may be able to reduce transmission,” says Hannaoui. “That could have important implications at the cervid population level.”

As CWD continues to spread, researchers say understanding how prion diseases behave, including the potential for silent or atypical infections, remains critical for protecting both wildlife and public health.

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Journal

Science Advances

DOI

10.1126/sciadv.aeb7613 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Limited transmission of cervid prions to nonhuman primates provides insights into the zoonotic potential of chronic wasting disease

 

The featherlight long-distance fliers with parchment-thin wings

Lund University

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Dragonflies and damselflies are predatory insects with powerful jaws, compound eyes and spectacular colours. What is less well known is their ability, like migratory birds, to travel long distances and overcome geographically challenging barriers such as the Indian Ocean and the Alps.

For a long time, scattered observations and papers have indicated migratory behaviour in a number of dragonfly species. Now, a comprehensive study of this global phenomenon has been completed. After several years of work and a review of 392 papers, the researchers have identified 100 species with documented migratory behaviour and a further 85 that are also likely to migrate. The results reveal a unseen world above our heads - where insects undertake journeys that can in some cases rival those of migratory birds.

“Many people see dragonflies as something that hovers over a forest pond for a few days in July. But some species fly across continents and open seas. It is truly staggering when you begin to grasp the scale,” says researcher Johanna Hedlund at Lund University, who led the study.

The research also shows that the ability to migrate has evolved several times over the course of evolution, mainly as a way to escape cold, drought, and environments where reproduction has become impossible. Most dragonflies, like other migratory insects, complete their round-trip migration over several generations. Others do something even more unusual: they fly from their hatching sites in hot valleys up to cooler elevations in the mountains - only to return later.

“I was genuinely surprised by how many examples there are of dragonflies completing an entire migration cycle, that is, a round trip journey, within a single lifetime. That is rare in insects and, oddly enough, something research has not paid much attention to before,” says Johanna Hedlund.

The researchers suggest that dragonflies can serve as guides to the vast, largely invisible mass migration of insects taking place globally. Because dragonflies are easy to recognise, they can help scientists understand how other insects move between ecosystems - from pollinating hoverflies to pests and disease vectors. Their migration routes can also reveal which environments are especially important to protect for migratory insects. In addition, dragonflies are sensitive to water quality and environmental changes, making them important indicator species.

“Dragonflies function almost like nature’s own sensors. By tracking their movements and where they thrive, we can better understand how ecosystems and the climate are changing,” concludes Johanna Hedlund.

FACTS: SPECTACULAR MIGRANTS

In Japan, the species Sympetrum frequens - the red dragonfly known as “Akiakane” - migrates from valleys up to cooler mountain areas during the summer, then returns again in the autumn. Another extreme migrant is the globe skimmer (Pantala flavescens), which is believed to carry out annual migrations between India, the Maldives and eastern Africa. These journeys take place partly over open ocean and cover thousands of kilometres.

Several migratory species are also found in Sweden, including the migrant hawker (Aeshna mixta) and the four-spotted chaser (Libellula quadrimaculata). At the same time, the vagrant emperor (Anax ephippiger) - a species originating from Africa and the Middle East - is being seen increasingly farther north in Europe, even in Sweden.

 

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Journal

Biological Reviews

DOI

10.1002/brv.70170 

Article Title

Flight of the dragons: a global review of migration in Odonata