From Smell Loss to Brain Fog

September 30, 2025 - By Rebecca Handler

As COVID-19 once again dominates national headlines, this time due to political disputes over vaccines, another pressing reality remains: millions of people continue to suffer from Long COVID.  The condition, now estimated to affect 10-30% of those who contract COVID-19, can manifest in everything from persistent headaches and fatigue to memory loss and gastrointestinal dysfunction. At the 2025 virtual symposium hosted by Stanford Medicine, leading researchers and clinicians gathered to discuss this enduring, shape-shifting illness. 

This year’s event, titled Unraveling Long COVID Care: Clinical Advances and Future Directions, brought together specialists from ENT, neurology, gastroenterology, hematology, psychiatry, psychology, speech therapy, physical therapy, and integrative medicine. It built on the foundation of Stanford’s 2024 webinar, Unraveling Long COVID: Advances in Clinical Practice, which featured a similarly multidisciplinary panel including experts in infectious diseases, neurology, cardiology, pulmonology, and sleep medicine. Both events underscore a growing movement to translate emerging research into meaningful, patient-centered care.

These efforts are part of a broader, ongoing commitment. In May 2021, Stanford opened the Post-Acute COVID-19 Syndrome (PACS) Clinic, a multidisciplinary effort launched in response to the growing numbers of patients who continued to experience COVID symptoms after their initial infection. Currently, the Stanford Long COVID Collaborative works with national networks to improve Long COVID care across clinical settings and support more standardized, equitable models of diagnosis and treatment, as well as host these grant-funded virtual symposiums 

Here, we share highlights from some of the symposium’s presentations to give a sense of the breadth of perspectives.

The Nose Knows: Smell Loss Offers Clues

Among the first speakers was Zara M. Patel, MD, professor of otolaryngology at Stanford and director of the university initiative to cure smell and taste loss. Her focus is on anosmia, or loss of smell, and the accompanying loss of taste, common in COVID infections. 

“People finally began to realize how critical these senses are for our safety, social lives, and overall well-being,” said Patel, who’s been studying olfactory dysfunction for over a decade. While loss of smell was once dismissed as an inconvenience, Patel’s work highlights its links to malnutrition, depression, and even a fourfold increased risk of mortality.

Patel presented research showing the effectiveness of olfactory retraining, a structured regimen where patients “exercise” their sense of smell by sniffing essential oils daily for six months. Her clinical trials show that patients who engage in this therapy, especially when combined with high-volume steroid nasal rinses and omega-3 supplements, are significantly more likely to regain their sense of smell.

She also touched on platelet-rich plasma (PRP), a therapy that repurposes the patient’s own blood to promote nerve regeneration. In a randomized controlled trial, those who received PRP injections had over 12 times the odds of regaining their sense of smell compared to those receiving a placebo. Many patients, she states, improve over time, likely due to the slow turnover of the olfactory neurons.

The implications go beyond COVID. “This opens the door for treating smell loss from a variety of causes — head injury, surgery, even aging and neurodegenerative diseases,” Patel noted.

When Migraines Become a Daily Occurrence 

Leon S. Moskatel, MD, a headache specialist, described a patient who’s become typical in Long COVID clinics: a patient whose occasional migraine attacks — once only a few days each month — turned into near-daily pain after they recovered from COVID.

“These patients often develop what we call a chronic migraine phenotype,” he said, meaning their headaches happen so frequently, that they meet criteria for migraine that occurs on 15 or more days per month.

Moskatel and his colleagues use a multi-pronged strategy to help people find relief.

First, they focus on lifestyle stabilization. That means helping patients keep consistent sleep and wake times, and eat regular meals. Second, they consider preventive medications taken regularly to reduce the overall headache burden. These can include non-specific oral medications originally developed to treat other diseases, but have established efficacy for the prevention of migraine. More recently, newer drugs have been developed specifically for migraine. These target a molecule called CGRP (calcitonin gene-related peptide), which plays a role in triggering migraine.

Third, they use acute treatments, such as medications or devices that help relieve a headache once it starts. These might include over-the-counter options like ibuprofen, prescription drugs like triptans or gepants that target migraine pathways, or even wearable devices designed to interrupt pain signals.

While there are some encouraging results, Moskatel cautioned that results are still mixed. “We focus on customizing therapy to each patient, so we can find the right approach that works for them.” 

Gut Instincts: A New Frontier in Long COVID Research

Next came John Gubatan, MD, a gastroenterologist whose research links COVID-19 to enduring gastrointestinal issues, ranging from irritable bowel syndrome to gastroparesis. “The GI tract is more than just collateral damage,” Gubatan said. “It may be a viral reservoir.”

According to data, up to 18% of patients report GI symptoms during acute infection, and many go on to develop functional disorders months later. These include diarrhea-predominant IBS, constipation, reflux, and functional dyspepsia, all without visible abnormalities on scans or endoscopy.

While the mechanisms remain unclear, the gut’s expression of ACE2 receptors, (the viral entry point for SARS-CoV-2), may be to blame, along with long-term microbiome disruption. Treatments are piecemeal for now, drawing from existing playbooks for IBS: dietary modifications, fiber, neuromodulators, and in some cases, antibiotics like rifaximin.

“COVID may be acting like a trigger, exposing underlying vulnerabilities in the brain-gut axis,” Gubatan explained. “We’re learning how to manage the symptoms, but we also need to better understand what’s driving them.”

Blood, Clots, and the Hidden Risk in Long COVID

Hematologist Beth Martin, MD, gave a compelling talk on how Long COVID may be driven not just by lingering virus, but by long-lasting changes in the blood and immune system. “Most of our vascular diseases aren’t just about clots,” she said. “They’re immune and inflammatory problems, and Long COVID appears to be no different.”

A big part of that problem involves something called NETs, short for neutrophil extracellular traps. These are sticky webs of DNA released by white blood cells to trap infections. “People who give lectures on this always show a Spider-Man slide,” Martin joked. While these webs are meant to protect us, in Long COVID they often stick around too long, clogging tiny blood vessels and causing ongoing inflammation. “Anticoagulation doesn’t seem to change outcomes over time,” she said. “We’re not dealing with your typical clots here.”

Martin also highlighted new findings about platelets, the cells that normally help stop bleeding. Scientists used to think of them as simple "patch-up" tools, but it turns out they play a much bigger role in the immune system. In Long COVID, they may actually help fuel inflammation. Even more surprising, Martin noted, is that many of these platelets are made in the lungs, not just in the bone marrow as once thought. “That’s a huge breakthrough,” she said. “Especially for a disease that starts in the lungs.”

She also discussed how Long COVID may trigger autoimmune reactions where the body starts attacking itself. Some patients develop antiphospholipid antibodies, which are proteins that make the blood more likely to clot. These can be hard to detect, and not every positive test is meaningful. “At first, we thought they were just noise,” Martin said. “But now, we’re seeing signs of a real autoimmune reaction — even if it doesn’t meet the textbook definition.”

So what’s next for treatment? Martin believes the real breakthrough will come from developing therapies that clear away these sticky immune webs and quiet the body’s overreactive immune system. “Our bodies don’t have a great way to clean this up,” she said. “And that may be why so many people stay sick long after the virus is gone.”

A Whole-Person Lens on Long COVID

Lauren Grossman, MD, offered a comprehensive and deeply humanistic lens on treating Long COVID. Drawing on her experience caring for critically ill COVID patients in the emergency department, as well as individuals with chronic fatigue and other complex conditions spanning multiple specialties, she integrates these perspectives through her work in integrative and lifestyle medicine.

“Long COVID is hard to describe, manifests differently in every person, and still affects 17 million U.S. adults as of 2024,” she said. Two million are out of work. “That’s a huge burden.”

Long COVID’s complexity, Grossman emphasized, comes not only from its long list of symptoms (more than 50 have been documented), but also from its tendency to affect nearly every organ system. She shared a symptom chart where fatigue, brain fog, and shortness of breath dominate, but even rarer symptoms, like paranoia, are represented. “This is from 2021,” she noted, “and anecdotally, I’d say far more than 58% have fatigue now.”

Grossman was candid about the failures of the healthcare system. “There’s no confirmatory test, no single fix, and no specialty that fully owns this condition,” she said. “It’s deeply frustrating for both patients and providers.” Many patients have gone through exhaustive testing with no answers, leaving them feeling dismissed. “That sense of not being heard — that’s where a whole-person approach comes in.”

Rather than chasing lab results, Grossman advocates for clinical listening and holistic assessment. She uses the Whole Person Health Index, a validated tool that tracks self-reported health across domains like sleep, stress, nutrition, and activity. From there, she assesses the full landscape: diet, medications, supplements, sleep, physical activity, stress, mood, cognitive function, and social connection. “It’s a lot,” she acknowledged, “but it helps us avoid the ‘kitchen sink’ approach where patients are thrown every therapy without a clear rationale.”

When it comes to brain fog, Grossman said, “It’s a hugely disabling issue, and one that’s hard even to define.” She looks for underlying causes such as nutritional deficiencies, hormonal shifts (especially in perimenopausal women), thyroid issues, and poor sleep. Speech therapists and neurocognitive testing are often helpful.

Grossman strongly cautioned against the “wild west” of supplements pushed by private clinics. “Some patients are spending thousands of dollars on supplements they don’t need,” she said. “That’s not ethical.”

Instead, she uses targeted therapies with clear rationales, such as magnesium for headaches, CoQ10 for mitochondrial support, and turmeric for inflammation. One pharmaceutical showing real promise? Low-dose naltrexone (LDN). “It’s been used in chronic fatigue and fibromyalgia for years, and we’re now finding that some Long COVID patients benefit at even higher doses.”

A Future Built on Listening and Learning

With the state of Covid vaccine research and recommendations currently up in the air, research into Long COVID prevention and treatment is now more vital than ever.

The Stanford symposium made one thing clear: there is no single profile for a Long COVID patient, and no one-size-fits-all solution. But across specialties, clinicians are starting to speak a shared language, one rooted in curiosity, compassion, and collaboration.