Paxlovid didn't fix long COVID in a randomized trial. Here's what that means.

Key Findings

Two Blood Markers Flag Who Isn't Getting Better 🩸

• In a cohort of 32 non-hospitalized long COVID patients, researchers tracked two markers over six months: GDF-15 (a mitochondrial stress signal) and VCAM-1 (a vascular stress marker).
• Both stayed persistently elevated in patients who hadn't improved by six months — while patients who recovered showed different trajectories. Most standard inflammatory markers stayed near detection limits and couldn't separate the groups.

Breathlessness Without a Visible Cause — Until Now 🫁

• The EXPLAIN study used hyperpolarized xenon MRI — a technique sensitive enough to detect gas exchange problems at the alveolar-capillary level — in never-hospitalized long COVID patients whose breathlessness had no identified cause on standard tests.
• The question: is there something physically wrong with the lungs that conventional imaging misses? The answer has implications for whether breathlessness in long COVID is structural, functional, or both.

Brain Noise and Cognitive Fatigue: A Measurable Signal 🧠

• Researchers measured auditory sensory gating — the brain's ability to filter out repetitive sounds — in long COVID patients using a marker called P50 suppression. Impaired gating has previously been linked to cognitive fatigue in multiple sclerosis.
• The study found impaired P50 suppression in long COVID, suggesting a neurophysiological correlate for the cognitive fatigue patients report. Objective markers for this symptom have been scarce.

Long COVID Patients Are Burning Through Healthcare 🏥

• A cross-sectional analysis of 76 post-COVID patients found a mean of 43.5 healthcare contacts per year and an average of 4.57 medications per patient. Nearly 40% met criteria for polypharmacy.
• Clustering analysis identified four distinct patient types. The smallest group — about 7% — averaged nearly 10 medications, 75 annual healthcare contacts, and over €2,800 in out-of-pocket costs. More medications strongly correlated with more doctor visits.

Smell Loss Is Measurable — But Patients Often Don't Know How Bad It Is 👃

• Two separate studies this week examined olfactory dysfunction in long COVID. One used machine learning to identify predictors of objective smell impairment severity and found a systematic shift in how affected patients rate odor pleasantness.
• The other compared self-reported smell and taste problems against objective measurements in long COVID patients versus uninfected and previously infected controls — probing how well patients' perceptions track their actual impairment.

Shared Biology Across Five Chronic Conditions 🔬

• A study using 3D genome architecture analysis found overlapping regulatory patterns across ME/CFS, long COVID, PTSD, rheumatoid arthritis, and multiple sclerosis — five conditions that share symptoms like fatigue, cognitive impairment, and immune dysregulation but are treated as distinct diseases.
• The finding suggests convergent biological pathways may underlie the symptom overlap, though the study is exploratory and the clinical implications remain to be worked out.