Long Covid Research Comes Out of the Shadows, Opens the Door to Improved Diagnosis Tools and Potential Therapies

The term “Long Covid” has been in the news even over the past month than in prior months as researchers published studies that suggest reasonably definitive diagnosis of the condition might be attainable.
Long Covid, a cognate that is a somewhat misleading term, began to be used by patients to describe a longer, more complex course of illness than that which had been reported in Wuhan and other early epicenters.
The term gained consistency in just a few weeks after its first use and many credit the term to Elisa Perego of Lombardy, a very hard-hit early hotspot, as a contraction of “long-term Covid illness.”  This, she felt, summarized her experience of the disease as cyclical, progressive, and multiphasic.
However, Long Covid remained a condition is currently a disease mostly defined by the symptoms which a patient presents with. Long Covid can include a wide range of health problems and these conditions can last weeks, months, or even years. The list of symptoms – which totals over 200 – can include severe chronic fatigue, brain fog (loss of executive function), organ damage, lightheadedness when standing, difficulty concentrating, difficulty breathing, shortness of breath, pins and needles pain, muscle pain, sleep issues, depression, and anxiety.
A study published in the journal Nature in September was heralded as a major step towards finally having a blood test to confirm a Long Covid diagnosis. Researchers at several institutions including Yale University’s Department of Immunobiology at its School of Medicine analyzed blood samples from almost 300 people, some of whom had Long Covid, some of whom had never had SARS-CoV-2, and some of whom had the virus and were fully recovered. Long Covid patients tended to have low levels of the stress hormone cortisol, and their blood also often suggested that virus lingered in their bodies. This could be caused either from remnants of the virus that causes SARS-CoV-2, or other viruses that had been dormant in the body after prior infections and become reactivated.
While it’s quite unlikely in my opinion that there will ever be a single biomarker for Long Covid, given how the condition presents so differently from individual to individual, the study used a machine-learning model that was trained to pick up on all of the potential signals together. As a result, it was able to distinguish the blood of Long Covid patients from those without the condition with 96% accuracy.
Meanwhile, Christoph Thaiss, an assistant professor of microbiology at the University of Pennsylvania’s Perelman School of Medicine, recently co-authored a study, Serotonin Reduction in Post-Acute Sequelae of Viral Infection, that was published last month in the journal Cell.
That study found another potential biomarker in the blood of Long Covid patients, namely low levels of serotonin, which is a monoamine neurotransmitter that is largely produced in the gut. Its biological function is rather complex and touches on diverse functions including mood, cognition, reward, learning, and memory, as well as on numerous physiological processes such as vasoconstriction and vomiting.
Using stool samples, Thaiss and his colleagues found genetic material from the SARS-CoV-2 virus in the gastrointestinal tracts of a subset of Long Covid patients, a finding that essentially mirrored results from other studies. They then hypothesized, and used mice to demonstrate, that this viral material can trigger an immune response that leads to excess inflammation in the body, in turn hampering the gut’s production of serotonin.  Inadequate serotonin seems to be a major contributor to a number of neurological symptoms of Long Covid.
There you have it.  These studies get us closer to an understanding of what takes place in the bodies of patients with Long Covid, including my own.
There’s a lot more work that has to be undertaken before we might see any early trials of treatments based on any of these findings but, as I am fond of saying, research is iterative.
Each repetition of a process is a single iteration, and the outcome of each iteration is then the starting point of the next iteration.
In the meantime, we will just have to be satisfied by pressing our thumbs for good luck.
[Editor’s Note: The curious among our readers – which would be most of them – will want to know why our intrepid editor mentioned “pressing our thumbs” versus “crossing our fingers.”  The phrase, in German “die Daumen drücken,” or “to press our thumbs,” is an expression that means to wish someone luck or success in a difficult matter  The gesture in numerous countries including Prof. Spira’s homeland, Austria, as well as Germany, Switzerland, Czechia, Slovakia, Slovenia, the Netherlands, Croatia, Sweden, South Africa, and Russia. The associated gesture involves holding the thumb between the other fingers and showing the gesture to the person whom you wish success to.  One can also wish oneself luck by holding or pressing one’s thumbs, for that matter.  The custom and expression goes back to the fact that one tends to involuntarily clench one’s hands when watching a competition or match of some sort where the individual in question strongly wants a particular person to triumph. –BA]
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