Food allergy, depression, Long COVID: Important steps toward objective diagnostics
Volume 8, Issue 15 | September 28, 2023
In This Issue
Best-practice guidelines for ALS counseling, testing, and treatment
Using tears to diagnose Parkinson’s
We need better sepsis diagnostics and more awareness
New and Noteworthy
A promising first step in the diagnosis of severe food allergies
Diagnosing food allergy is hard. What’s been even harder has been figuring out who’s at risk of a severe, potentially life-threatening allergic reaction to food and who is likely to have only mild symptoms. A small study published last month in the Journal of Allergy and Clinical Immunology may have found a biomarker that can distinguish between the two.
Researchers looked at the tryptase enzyme. It’s produced and released by mast cells, a part of the immune system that is activated during allergic reactions. Tryptase comes in two forms: alpha and beta. Among the 119 food-allergic subjects studied, people who had alpha-tryptase in their blood were significantly more likely to have severe allergic reactions than those who had only the beta form.
Proof-of-concept for a potential diagnostic test for depression
As widespread as it is, depression remains an enigma, both in terms of treatment selection, which remains hit-or-miss, and in terms of monitoring, which relies on patient self-reporting. A reliable biomarker would revolutionize both.
This week a study in Nature presented an AI-empowered diagnostic tool for depression. While very small (10 treatment-resistant patients with major depressive disorder (MDD) tracked for 24 weeks), the results were promising.
Drawing on data obtained through the use of implanted electrodes (used to provide therapeutic deep-brain stimulation (DBS)), the tool was able to both “identify the brain patterns associated with severe depression,” and flag “a distinct change in neural activity that could distinguish between the two states (depression versus recovery) with an accuracy of more than 90%,” as a companion perspective in Nature reported. It also showed that after successful treatment, one patient’s brain switched back to a pre-treatment pattern a month before the patient clinically relapsed - thus identifying a way to predict and potentially ward off relapse.
Early signs of a Long COVID AI-embedded diagnostic?
Fully one in eight acute COVID infections leads to persistent COVID symptoms, and methods to consistently either diagnose or treat the syndrome have thus far remained frustratingly elusive. But things may be finally looking up.
A study released by Nature this week reports the first success at identifying immune system biomarker combinations that distinguish Long COVID (LC) cases from those with no persisting symptoms. There have been many proposed hypotheses about what might cause LC, and this paper’s results discount several of them - specifically LC is unlikely to be an autoimmune flare-up, and equally unlikely is a persisting hidden pocket of SARS virus. LC sufferers seem to have lower overall immune vigilance against novel pathogens (low cortisol and fewer dendritic cells), while maintaining hypervigilance (high monocyte counts and inflammatory cytokines) against repeat encounters with SARS-CoV-2 and other previously encountered viruses (e.g., herpes, Epstein-Barr). Of all the potential biomarkers identified, low cortisol was most predictive of LC (with an AUC of 0.96). Low cortisol alone is known to be enough to drive the top four symptoms of LC - fatigue, brain fog, poor memory and confusion.
Commentary: Understanding the human immune system for Long COVID patients is a huge step forward. Developing a diagnostic that distinguishes the underlying causes is the next step and will likely require AI-embedded analysis of even larger data sets.
Tears bring diagnostic clarity for Parkinson’s disease
One of the recent advancements in diagnostic technology has been the use of new, less invasive sample types. During the pandemic we saw nasopharyngeal swabs lose ground to the less “brain-tickling” anterior nasal swabs and increased use of saliva. These days, we are seeing more tests using breath, hair, and skin for diagnosis.
Another newly ascendant sample type is tears. Back in May we reported on a study that used tear fluid to diagnose variant Creutzfeld-Jakob disease (the human form of mad cow disease). This month the FDA approved a point-of-care diagnostic for Parkinson’s disease that analyzes tears for the presence of a recognized biomarker known to appear in tear fluid, alpha-synuclein.
Food for Thought
We need better diagnostics for sepsis - and more attention on the syndrome
Of the four screening tools for sepsis recommended by the Society of Critical Care Medicine’s Surviving Sepsis Campaign Guidelines, only one accurately predicted sepsis with more than 50% sensitivity (the National Early Warning Score (NEWS-2, at 72.2%), according to research presented last week at the European Emergency Medicine Congress. Silke Piedmont, one of the authors of the Berlin-based study, also noted that “paramedics never documented a suspicion of sepsis,” and ER doctors did so in only 0.1% of cases.
Commentary: We’ll let Wolfgang Bauer, another of the study’s authors, take the mic: “There was a similar incidence for sepsis, 1.6%, as for heart attacks, 2.6%, and stroke, 2.7%, in cases seen by emergency medical services. However, in terms of both percentages and absolute numbers, more patients died from sepsis than from heart attacks or stroke. Out of all cases with sepsis, 31.4% died within 30 days after being seen by emergency services, versus 13.4% and 11.8% respectively for heart attacks and stroke. These findings emphasize the need for better sepsis awareness and more frequent use of effective screening tools.” Yeah. What he said.
To get people to do genetic tests for ALS, give them a road map
Increasing genetic testing for patients with amyotrophic lateral sclerosis (ALS) has not been easy. Somehow, even advances in gene discovery and progress in gene therapy trials have not boosted demand.
In an effort to change that, the ALS Genetic Testing and Counseling Guidelines Expert Panel has published a set of 35 guidelines for the best practices in counseling, testing, and treatment of amyotrophic lateral sclerosis (ALS). The core of the recommendations are focused on increasing access, understanding, and use of genetic testing.
The guidelines also included recommendations for reporting: A clinician or counselor should deliver the results and ensure that the patient / family understands the potential of false negatives and that interpretation may change overtime as more information is developed about specific mutations.
Commentary: Kudos to the Expert Panel for taking the initiative to create and publish these guidelines. For diseases as tough as ALS (and others), physicians and patients (and their families) look to experts for guidance. Experienced and inexperienced physicians want a recognized roadmap for their patients. We hope that more disease associations do the same.
Quick Hits
Last week, the CDC announced the recipients of 13 funding awards (for a total of $262.5 million over five years) to establish a national Outbreak Analytics and Disease Modeling Network. The network will not involve the development of disease diagnostics - instead, it will focus on outbreak analytics and disease modeling for public health use, as well as on preparation for and response to infectious disease threats.
Re: the quick hit: Go blue!