RECOVER researchers shared how the prescription drug metformin may reduce the risk of Long COVID and presented research examining the risk of developing myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after a COVID-19 infection.
A recent RECOVER Research Review (R3) Seminar held May 13 spotlighted research presented by Carolyn Bramante, MD, MPH (University of Minnesota) and Steve Johnson, PhD (University of Minnesota) exploring how metformin, a widely prescribed medication primarily used to manage type 2 diabetes, may help reduce the risk of Long COVID. The seminar also featured a presentation from Suzanne Vernon, PhD (Bateman Horne Center) on research examining the risk of developing myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) following a COVID-19 infection.
Drawing from both large-scale electronic health record (EHR) networks and RECOVER’s adult observational study, these studies illustrate critical links among COVID-19, persistent post-viral conditions, and potential prevention strategies involving available pharmaceutical drugs. While metformin’s exact mechanisms are still being explored by researchers, evidence supporting its use during acute COVID-19 infection continues to grow.
Drs. Bramante and Johnson led an EHR study analyzing data from the National COVID Cohort Collaborative (N3C) and the National Patient-Centered Clinical Research Network (PCORnet). Their study focused on adults with type 2 diabetes. They compared Long COVID outcomes between individuals already taking metformin and those using other diabetes medications, a type of study design known as “prevalent user, active comparator.” In other words, the researchers aimed to evaluate the association between pre-existing metformin use and the risk of developing Long COVID. Results showed a consistent trend: individuals on metformin were less likely to develop Long COVID compared to those not taking the drug. These findings aligned with earlier clinical trial data, including a randomized controlled study conducted by Dr. Bramante and the University of Minnesota’s COVID-OUT Study Team, which reduced Long COVID incidence by 31% through early metformin treatment.
Dr. Bramante noted that many clinicians remain unaware of metformin’s potential role beyond diabetes management. Although prescribing metformin off-label for COVID-19 prevention is legally permissible, this guidance is not yet reflected in most COVID-19 treatment guidelines—some of which are based on earlier clinical trials with less definitive results.
Dr. Vernon presented research findings from the RECOVER adult observational study examining risk of developing ME/CFS following a COVID-19 infection. ME/CFS is a chronic, disabling illness that includes symptoms such as severe fatigue; tiredness that gets much worse after physical, mental, or emotional activity; sleep that is not deep or restful; trouble remembering, learning new things, concentrating, or making decisions; and dizziness or other problems resulting from standing upright. Using the 2015 ME/CFS clinical diagnostic criteria from the National Academy of Medicine (formerly the Institute of Medicine), Dr. Vernon and her team found that:
- Approximately 1 in 20 people who had COVID-19 met the criteria for ME/CFS 6 months after infection.
- The estimated number of US adults with ME/CFS is over 15 million, compared with an estimate of about 3 million adults who had ME/CFS before the COVID-19 pandemic.
- Risk for ME/CFS was significantly higher among those who had a SARS-CoV-2 infection compared to individuals who did not have an infection in the study.
- ME/CFS cases were concentrated within the subgroups of Long COVID patients who displayed the greatest number of observable symptoms.
Dr. Vernon emphasized that medical teams must consider ME/CFS among the various diagnosable conditions that often follow COVID-19. RECOVER’s robust biosample collection and longitudinal studies provide an unprecedented opportunity to study how ME/CFS affects the body’s normal functioning. These resources also may provide the opportunity to develop diagnostic biomarkers for the condition, or indicators of ME/CFS that clinical laboratory tests can identify and that reliably pinpoint the presence of the condition.