The ride with COVID-19 has been a twisting one, and not all have been enjoyable. Perhaps the oddest, most unforgettable symptom has been a loss of taste and smell. For many, these came back within weeks. For some, though, the alterations lingered, as a constant reminder of illness and contributing factor in what we now refer to as long COVID. Figuring out why this occurs and what it suggests for recovery is a key part of the continuing research puzzle.
A Close-Up of the Tongue
A new study published in Scientific Reports went deep on this problem, looking at the foliate papillae, a small but significant component of the tongue. Scientists were curious whether past SARS-CoV-2 infection, quantified by IgG antibody levels, was associated with gene expression changes in that region.
They compared four groups of individuals:
- Those with antibodies and sensory impairment.
- Those with antibodies but without sensory impairment.
- Those who had no antibodies but complained of sensory symptoms.
- Those with antibodies but no sensory issues.
This robust study design enabled scientists to unwind COVID-related alterations from other origins. Through self-reported surveys, taste tests, and RNA expression analysis, they were able to trace the biological signatures associated with sensory loss.
What the Study Found
Patients who had antibodies and residual taste or smell difficulties evidenced particular sensory deficits particularly with metallic taste. That’s not a matter of perception; it signifies underlying biological alterations.
Far-reaching gene alterations: More than 5,300 genes had reduced RNA expression, and around 790 were elevated in comparison with control groups. This indicates widespread repression of gene function within the papillae of the tongue following infection.
Olfactory receptors on the tongue: In a surprise twist, 166 olfactory receptor genes typically found in the nose had lower expression levels. Some, such as OR1A2 and OR2J2, are connected to metallic taste, leaving intriguing questions regarding how these receptors would operate on the tongue.
Taste receptor variations: Receptors associated with umami (TAS1R1) and bitter taste (eight TAS2R receptors, including TAS2R7) were reduced. This correlated with decreased sensitivity in taste tests.
Stress response genes: Certain genes, such as MTF1 (a metal balance and stress regulator), were more highly expressed, perhaps indicating a struggle by the tongue tissue to adapt.
In brief, the work presents strong biological evidence that long COVID taste and smell abnormalities aren’t “in people’s heads” they’re associated with quantifiable genetic modifications in tongue tissues.
The Bigger Picture of Long COVID
Of course, sensory loss is only one piece of the long COVID puzzle. Millions worldwide face an exhausting range of symptoms:
- Severe fatigue.
- Brain fog that disrupts daily functioning.
- Chest pain and breathing difficulties.
- Digestive problems and heart issues.
- Higher rates of depression and anxiety.
For many, these symptoms persist for months or even years. Unfortunately, they’re often misunderstood or dismissed by doctors, employers, and sometimes even loved ones. That lack of recognition adds to the suffering. Living with an “invisible illness” can be especially cruel because others may assume you’re fine, when in reality, your body is still fighting.
Validation and Care
Dr. Hector Bonilla, co-director of the Stanford Post-Acute COVID-19 Syndrome Clinic, likens the plight of long COVID patients to patients with chronic fatigue syndrome (CFS). He emphasizes that medicine has in the past been at a loss to treat conditions such as CFS, and long COVID is a case of déjà vu.
What most patients require, he emphasizes, is validation. Telling them, “Yes, I hear you. You’re not alone millions of others are going through this too” can be a lifesaver. Without that, the disease has wrecked careers and even marriages, adding to its burden. Sincere empathy on the part of doctors can at times be as therapeutic as any medical treatment itself.
The Economic Impact
The symptoms of long COVID extend far beyond the clinic. According to health economist Dr. Gopi Shah Goda, lost labor supply from long COVID costs the U.S. economy approximately $62 billion each year. To get a perspective on that figure, that’s almost as much productivity loss due to cancer or diabetes.
But while cancer and diabetes research are funded in the billions annually by the NIH, long COVID research remains underfunded. On top of that, many sufferers fail to meet contemporary disability insurance standards, leaving them economically stranded regardless of debilitating health issues. For working-age adults, this is a bitter double bind: too ill to make a living, yet not ill enough from the perspective of administrative systems to be helped.
Policy and Workplace Gaps
With the expiration of COVID’s public health emergency and lenient isolation protocols, professionals fear the issue will only get worse. Employees who have no paid sick leave might be compelled to decide between their well-being and their employment. Because of this, policies to support and shield long COVID sufferers are becoming increasingly pressing.
Some awareness efforts are helping. Long COVID Awareness Day has gained traction, and U.S. Senate hearings have started spotlighting the issue. Sen. Bernie Sanders put it bluntly: “There’s a sense that something serious is happening in America, and we’re not doing enough about it.” His comments highlight that long COVID is not just a medical issue, but also a social and economic one that requires systemic solutions.
Searching for Treatments
As of now, there are no medications officially approved for long COVID. Doctors are nevertheless trying existing medication. At Stanford, Dr. Bonilla has found success with:
- Low-dose naltrexone – an immunomodulatory medication.
- Low-dose Abilify – an antipsychotic that can help with neurological symptoms.
Simultaneously, the NIH’s CureID program is collecting real-world data to inform future clinical trials. These initial attempts can one day lay the groundwork for more uniform treatment guidelines, but currently, patients most often use trial-and-error methods with physicians.
Innovative Diagnostics on the Horizon
In addition to treatments, diagnostics are also becoming advanced. One such new study investigated the potential of using carbon dots (CDs) nanoparticles created from citric acid and APBA as diagnostic tools for identifying COVID antibodies.
Here’s what scientists discovered:
- The CDs bind well with antibodies, altering their fluorescence and absorbance.
- They create a stable complex by reacting with chemical groups on antibodies.
- The approach was 74% sensitive and 53% specific for the detection of IgG.
Even though it is early, this technology has the potential to provide cheap, biocompatible screening devices particularly worth their salt in low-resource environments. In contrast to sophisticated lab tests, CDs may one day provide fast, mobile, and relatively low-cost means of tracking COVID-19 exposure or immunity.
Why Continued Research Matters
Even as the public sphere continues beyond COVID, the virus itself continues to adapt. New variants, such as XEC toward the end of 2024, serve as a reminder that complacency is not an option. Good science on long COVID, diagnosis, and treatment is essential, both for individuals and for society. Neglecting these causes risks leaving millions of people behind and allowing the economic damage to mushroom.
The Road Ahead
From the molecular alterations occurring on our tongues to the economic hardship faced by workers displaced by disease, COVID’s long shadow continues to transform lives. But things are changing:
- Science is revealing the genetic origins of sensory loss.
- Clinicians are testing potential treatments.
- Economists are putting dollar estimates on the costs to spur policy action.
- Innovators are creating new diagnostic tests.
The journey is not yet done, but with each study, each clinic, and each campaign raising awareness, we move closer to answers. By continued persistence, compassion, and investment, the world can proceed toward improved diagnosis, treatment, and care for all persons living with long COVID. What we learn today will not only guide us in managing this condition but will also equip us for managing future public health crises that require science and humanity.
